第４章の⼩括

第４章では、残る類縁体であるstrophasterol D及びglaucoposterol Aの合成に取り組 んだ(Scheme 41)。オキシム78に対し、PhI(OAc)2を⽤いた1,3-双極⼦付加環化反応に 付すと、79A と79Bがほぼ同じ⽐率で得られることが分かった。その後 strophasterol

C, F を合成した際の⼿法に準拠して 79B のイソオキサゾリン環の開裂とB 環の官能

基修飾を⾏い、glaucoposterol Aの提唱構造11及びstrophasterol Dの推定構造8を合成 した。しかしながら両者の各種NMRスペクトルは天然物とは⼀致しなかった。そこ でNMRスペクトルの詳細な⽐較を⾏い、glaucoposterol Aの真の構造はstrophasterol F と同⼀であると結論づけた。また、strophasterol D の真の構造は、推定構造 8 の合成

の結果、strophasterol Cの７位に関するエピマー144であるということが⽰唆されたた

め、実際に144を合成して天然のstrophasterol Dと⽐較した。その結果、strophasterol

AcO

O H

H TESO

O OTES

TsOH CH₂Cl₂/EtOH

rt, 87%

104

AcO

O H

H HO

O OH 145

AZADOL, NaOCl KBr, NaHCO₃ CH₂Cl₂, H₂O, rt

61%

AcO

O H

H O

O O 146

NaBH₄ MeOH, 0 ºC

AcO

O H

H O

O OH 147

HO

O H

H O

O OH

Mg MeOH, 50 ºC

HO

O H

H O

O OH strophasterol C

(2 steps 60%)

144 (strophasterol D)

(2 steps 15%)

+

lit. [α]²⁴_D = –15.0 (c 0.02 MeOH) [α]²⁴_D = –18.3 (c 0.14 MeOH)

Dの⽴体化学は144であるという結論に達した。

Scheme 41. 第４章の⼩括

AcO

O

AcO

O 1,3-dipolar

cycloaddition

79A

73 H

H

H

HO H

O O OH

H

strophasterol D (X = Y = O, putative) glaucoposterol A (X = H, Y = OH)

N O

HO H

O AcO

N O

H

78 H

OH

H YX

B-ring functionalization

AcO

O 79B H

H N

H H O

PhI(OAc)₂

(1.2 : 1)

HO

O O OH

H H HO

HO

O O OH

H H HO

strophasterol F (10) ( glaucoposterol A ) glaucoposterol A (11)

(proposed structure)

revise

AcO

O

104 H

O

H TESO

O

HO

O O OH

H H O

144 strophasterol D OTES

4 steps

第５章 総括

著者は 15(14→22) abeo-エルゴスタン⾻格という特異な転位型ステロイド構造を有

し、キノコの⼦実体形成誘導ホルモンである可能性を秘めた strophasterol類に興味を 持ち、それらの合成を達成するとともに、⽣物学的研究へ供することを⽬的に研究に 取り組んだ(Figure 8)。本合成研究の過程で、ステロイド⾻格D環の開裂法や新規⾻格 の特徴を成す D’環の2種の構築法、さらにステロイド⾻格 B 環へのエポキシアルコ ール構造の効率的な導⼊法の確⽴に成功し、有機合成化学領域の進展に貢献できたも のと考える。これまでにstrophasterol A–Fの合成を達成し、strophasterol A及びBに関 しては⽣物学的研究のための標品供給をすることができた。また「NMR 的⼿法及び

⽣合成的考察によって構造決定がなされていたstrophasterol Cの構造が正しいこと」、

「glaucoposterol Aの構造がstrophasterol Fと同⼀であること」、そして「strophasterol D の真の構造がstrophasterol Cの7位に関するエピマーであること」を合成化学的に明 らかにし、天然物の構造決定における有機合成化学の役割を果たすことができた。今 後は本博⼠論⽂研究において合成した 6 種の天然物及び合成中間体等を⽣物学的試 験に供し、構造活性相関研究へと展開していく予定である。また ergosterol からの誘 導ではなく、strophasterol 類及び関連物質の効率的全合成による供給についても研究 が進展することを期待している。

Figure 8. 総括

HO

O H O OH

C22β : strophasterol A C22α : strophasterol B

HO

O H O OH

strophasterol C

HO

O H O OH

strophasterol D

O O

HO

O H O OH

glaucoposterol A HO

H

HO

O H O OH

strophasterol E HO

HO

O H O OH

strophasterol F HO

H H

H

22 H

=

7

strophasterol F

引⽤⽂献

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実験の部

General Information

IR spectra were recorded by a Jasco FT/IR-4100 spectrometer using an ATR (ZnSe) attachment.

NMR spectra were recorded with TMS as an internal standard in CDCl3 by a Varian 400-MRTT spectrometer (400 MHz for ¹H and 100 MHz for ¹³C), a Varian 600TT spectrometer (600 MHz for ¹H and 150 MHz for ¹³C), or JEOL JNM-ECS400 (400 MHz for ¹H and 100 MHz for ¹³C) unless otherwise stated. Optical rotation values were measured with a Jasco P-2200 polarimeter.

Mass spectra were obtained with JEOL JMS-700 spectrometer operated in the EI or FAB mode or a Bruker Daltonics microTOF-Q II instrument (ESI). Melting points were determined with a Yanaco MP-J3 apparatus and are uncorrected. Merck silica gel 60 (63–200 mm) or Kanto Kagaku silica gel 60N (100–210 mm) was used for column chromatography. Analytical thin-layer chromatography was performed using Merck silica gel 60 F254 plates (0.25 mm thick).

Solvents for reactions were distilled prior to use: THF from Na and benzophenone; CH2Cl2

from CaH2; benzene and hexane from LiAlH4; MeOH from Mg(OMe)2; EtOH from Na and diethyl phthalate. All air- or moisture-sensitive reactions were conducted under a nitrogen atmosphere.

Experimental Procedures and Characterization Data

(3S,5S,10S,13R,17R)-17-((2R,5R,E)-5,6-dimethylhept-3-en-2-yl)-10,13-dimethyl-2,3,4,5,6,7,10,11,12,13,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate (28)

To a stirred solution of ergosterol (25.0 g, 63.0 mmol) in CHCl3 (250 mL) was added HCl (1.25 M in MeOH, 54.5 mL, 68.1 mmol) at 60 ºC and the mixture stirred for 5 h. The mixture was quenched with satd aq NaHCO3 and extracted with CHCl3. The extract was washed with water and brine, dried (MgSO4) and concentrated in vacuo to give crude 40 as a white solid witch was used in the next step without further purification. To a stirred solution of 40 (25.0 g, 62.7 mmol) in pyridine (160 mL) was added AcCl (4.88 mL, 75.3 mmol) at room temperature and the mixture was stirred at same temperature for 2 h. The mixture was quenched with satd aq NH4Cl and extracted with CHCl3. The extracted was washed with water and brine, dried with (MgSO4) and concentrated in vacuo. The residue was purified by SiO2 column chromatography (hexane/EtOAc = 10:1) to give 28 (24.9 g, 90% from ergosterol) as a white solid. Mp 145–146 °C; [a]²⁰D –54.6 (c 1.57, CHCl3); IR: nmax 3053 (w), 1730 (s), 1371 (m), 1265 (s); ¹H NMR (400 MHz): d 0.81–0.86 (9H, m), 0.93 (3H, d, J = 6.8 Hz), 1.00 (3H, s), 1.04 (3H, d, J = 6.6 Hz), 1.30 (1H, dt, J = 4.2, 13.6 Hz), 1.37–1.62 (8H, m), 1.69–1.75 (1H, m),

HO

H

ergosterol ^HO

HCl H MeOH

CHCl₃, 70 ºC H 40

H H

AcO

H

H 28

AcCl pyridine, rt 2 steps 90%

1.83–1.93 (3H, m), 1.96–2.41 (11H, m), 4.71 (1H, tt, J = 5.4, 11.0 Hz), 5.20 (1H, dd, J = 7.6, 15.2 Hz), 5.26 (1H, dd, J = 7.0, 15.2 Hz), 5.34 (1H, br s); ¹³C NMR (100 MHz): d 15.8, 17.6, 18.2, 19.6, 19.9, 20.9, 21.4, 21.7, 25.1, 26.5, 27.6, 33.0, 34.1, 35.0, 36.5, 36.6, 36.8, 38.9, 40.7, 42.8, 44.7, 57.0, 73.3, 117.9, 123.2, 132.0, 135.5, 140.3, 150.7, 170.6; HRMS (EI): m/z calcd.

for C30H46O2, 438.3498; found, 438.3501 (M⁺).

(3S,5S,9S,10S,13R,17R)-17-((2R,5R,E)-5,6-dimethylhept-3-en-2-yl)-9-hydroxy-10,13-

dimethyl-15-oxo-2,3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate (29)

To a stirred solution of 28 (0.439 g, 1.00 mmol) in acetone (32.0 mL) was added dropwise Jones reagent (2.65 M, 0.80 mL, 2.12 mmol) for 30 min at room temperature and the mixture was stirred for 30 min. The mixture was quenched with 2-propanol and diluted with water. It was concentrated in vacuo and extracted with ether. The extract was washed with water and brine, dried (MgSO4) and concentrated in vacuo. The residue was purified by SiO2 column chromatography (hexane/EtOAc = 8:1) to give 29 (0.207 g, 44%) as white amorphous solid.

Mp 197–198 °C; [a]²⁰D +110 (c 1.38, CHCl3); IR: nmax 3471 (m), 1722 (s), 1687 (s), 1620 (m), 1252 (s); ¹H NMR (400 MHz): d 0.80–0.85 (9H, m), 0.91 (3H, d, J = 6.8 Hz), 0.98 (3H, s), 1.10 (3H, d, J = 6.7 Hz), 1.22–1.37 (2H, m), 1.39–1.66 (8H, m), 1.72–2.08 (11H, m), 2.13–2.24 (2H, m), 2.29 (1H, dd, J = 8.0, 19.2 Hz), 3.92 (1H, ddd, J = 2.0, 4.5, 14.6 Hz), 4.72 (1H, tt, J = 5.4, 11.0 Hz), 5.16 (1H, dd, J = 8.5, 15.3 Hz), 5.27 (1H, dd, J = 7.9, 15.3 Hz); ¹³C NMR (100 MHz):

d 15.5, 17.5, 17.7, 19.7, 20.0, 21.4 (2C), 22.6, 26.9, 27.8, 28.3, 29.4, 33.0, 33.5, 33.7, 35.1, 39.2, 41.3, 42.91, 42.93, 43.0, 50.5, 72.9, 74.3, 133.6, 134.0, 141.6, 148.0, 170.6, 208.4; HRMS (EI):

m/z calcd. for C30H46O4, 470.3396; found, 470.3399 (M⁺).

AcO

H OH O

Jones reagent acetone

rt, 44%

H 29 AcO

H

H 28

(3S,5S,9R,10S,13R,17R)-17-((2R,5R,E)-5,6-dimethylhept-3-en-2-yl)-10,13-dimethyl-15-oxo-2,3,4,5,6,7,9,10,11,12,13,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate (30)

To a stirred solution of 29 (0.104 g, 0.212 mmol) in MeOH (4.0 mL) and CH2Cl2 (1.0 mL) was added zinc dust (0.139 g, 2.12 mmol) in portions for 1 h. A solution of conc. H2SO4 (0.11 mL, 2.12 mmol) in MeOH (1.0 mL) was added dropwise during the same time. The slurry was neutralized with solid NaHCO3, filtered off and concentrated in vacuo to remove MeOH. The residue was dissolved in CH2Cl2 and washed with water and brine, dried (MgSO4) and concentrated in vacuo. The residue was purified by SiO2 column chromatography (hexane/EtOAc = 10:1) to give 30 (0.0828 g, 86%) as a white solid.Mp 160 °C; [a]²⁰D +65.7 (c 1.08, CHCl3 ); IR: nmax 1739 (s), 1698 (s), 1623 (m), 1264 (s); ¹H NMR (400 MHz): d 0.73 (3H, s), 0.82 (3H, d, J = 6.9 Hz), 0.84 (3H, d, J = 7.0 Hz), 0.91 (3H, d, J = 6.8 Hz), 0.99 (3H, s), 1.09 (3H, d, J = 6.6 Hz), 1.20–1.78 (14H, m), 1.80–1.91 (3H, m), 1.98–2.28 (7H, m), 4.12 (1H, ddd, J = 1.9, 4.1, 14.2 Hz), 4.73 (1H, tt, J = 5.4, 11.0 Hz), 5.16 (1H, dd, J = 8.5, 15.3 Hz), 5.26 (1H, dd, J = 7.8, 15.3 Hz); ¹³C NMR (100 MHz): d 12.7, 17.6, 18.8, 19.4, 19.5, 19.9, 21.26, 21.34, 27.1, 27.3, 28.9, 32.9, 33.5, 36.1, 36.7, 38.5, 39.2, 42.2, 42.77, 42.79, 43.8, 50.6, 50.7, 73.0, 133.1, 134.2, 140.2, 149.9, 170.4, 207.7; HRMS (EI): m/z calcd. for C30H46O3, 454.3447;

found, 454.3444 (M⁺).

(3S,5S,9R,10S,13R,17R)-17-((2R,5R,E)-5,6-dimethylhept-3-en-2-yl)-3-hydroxy-10,13-

dimethyl-1,2,3,4,5,6,7,9,10,11,12,13,16,17-tetradecahydro-15H-cyclopenta[a]phenanthren-15-one (30’)

AcO

H O Zn, H₂SO₄

MeOH, CH₂Cl₂

rt, 86% _H

30 H AcO

H

OH O H 29

To a stirred solution of 30 (2.89 g, 6.36 mmol) in MeOH (140 mL) and water (70 mL) was added K2CO3 (1.76 g, 12.7 mmol) at 80 ºC and the mixture was stirred for 2 h at the same temperature. The mixture was concentrated in vacuo to remove MeOH and extracted with CHCl3. The extract was washed with water and brine, dried (MgSO4) and concentrated in vacuo.

The residue was purified by SiO2 column chromatography (hexane/EtOAc = 3:1) to give 30’

(1.91 g, 73%) as a white solid. Mp 157–158 °C; [a]²⁰D +81.7 (c 0.50, CHCl3); IR: nmax 3417 (br), 1704 (s), 1623 (s), 1455 (m); ¹H NMR (400 MHz): d 0.72 (3H, s), 0.82 (3H, d, J = 7.0 Hz), 0.83 (3H, d, J = 7.0 Hz), 0.91 (3H, d, J = 6.9 Hz), 0.99 (3H, s), 1.09 (3H, d, J = 6.6 Hz), 1.15–

1.76 (15H, m), 1.80–1.90 (3H, m), 1.99–2.28 (4H, m), 3.65 (1H, tt, J = 5.2, 10.7 Hz), 4.09–

4.16 (1H, m), 5.16 (1H, dd, J = 8.5, 15.4 Hz), 5.26 (1H, dd, J = 7.8, 15.4 Hz); ¹³C NMR (100 MHz): d 12.8, 17.6, 18.9, 19.5, 19.6, 19.9, 21.4, 27.5, 29.1, 31.0, 32.9, 36.5, 36.8, 37.7, 38.7, 39.1, 42.3, 42.84, 42.85, 44.1, 50.8, 50.9, 70.7, 133.2, 134.2, 140.2, 150.5, 207.9; HRMS (EI):

m/z calcd. for C28H44O2, 412.3341; found, 412.3340 (M⁺).

(3S,5S,8R,9S,10S,13R,14S,17R)-17-((2R,5R,E)-5,6-dimethylhept-3-en-2-yl)-3-hydroxy-10,13-dimethylhexadecahydro-15H-cyclopenta[a]phenanthren-15-one (31)

To a stirred solution of Li (1.11 g, 160.0 mmol) in NH3 (300 mL) was added a solution of 30’

(3.00 g, 7.28 mmol) in THF (80 mL) at –78 ºC and the mixture was stirred for 1.5 h at the same temperature. The mixture quenched with solid of NH4Cl and stirred room temperature to

K₂CO₃ MeOH/H₂O 60 ºC, 73%

AcO

H

O H 30

H

HO

H

O H 30’

H

HO

H

O 31 H H

H

H Li, liq. NH₃

THF, –78 ºC HO 80%

H

O H 30’

H

remove NH3. The mixture was extracted with EtOAc and washed with water and brine, dried (MgSO4) and concentrated in vacuo. The residue was purified by SiO2 column chromatography (hexane/EtOAc = 5:1) to give 31 (2.31 g, 80 %) as a white solid.Mp 183–184 °C; [a]²⁰D +11.1 (c 0.13, CHCl3); IR: nmax 3419 (br), 1733 (s), 1457 (w); ¹H NMR (400 MHz): d 0.60–0.68 (1H, m), 0.76 (3H, s), 0.79–0.85 (9H, m), 0.90 (3H, d, J = 6.8 Hz), 0.98 (1H, dt, J = 3.8, 13.4 Hz), 1.04–1.89 (22H, m), 2.06–2.17 (2H, m), 2.29 (1H, dd, J = 8.7, 18.8 Hz), 2.65 (1H, dq, J = 13.1, 3.3 Hz), 3.59 (1H, tt, J = 5.3, 10.8 Hz), 5.13 (1H, dd, J = 8.4, 15.4 Hz), 5.24 (1H, dd, J = 7.8, 15.3 Hz); ¹³C NMR (100 MHz): d 12.2, 13.2, 17.7, 19.6, 20.0, 20.8, 21.3, 28.2, 29.7, 30.6, 31.4, 31.9, 33.0, 35.6, 36.9, 38.1, 39.8, 42.2, 42.3, 42.9, 44.8, 51.2, 54.0, 66.0, 71.2, 133.3, 134.3, 216.2; HRMS (EI): m/z calcd. for C28H46O2, 414.3498; found, 414.3498 (M⁺).

(3S,5S,8R,9S,10S,13R,17R)-17-((2R,5R,E)-5,6-dimethylhept-3-en-2-yl)-3,14-dihydroxy-10,13-dimethylhexadecahydro-15H-cyclopenta[a]phenanthren-15-one (32)

To a stirred solution of 31 (1.89 g, 4.76 mmol) in CH2Cl2 (63 mL) was added HMDS (14.9 mL, 71.4 mmol), LiI (2.24 g, 16.7 mmol) and TMSCl (6.08 mL, 47.6 mmol) at room temperature and stirred for 2 h at the same temperature. The mixture was quenched with Et3N and extracted with CH2Cl2. The extract was washed with water and brine, dried (MgSO4) and

TMSCl HMDS, LiI CH₂Cl₂, rt

HO

H

OHO H

H H HO

H

O 31 H H

H

H

mCPBA, NaHCO₃ CH₂Cl₂, rt then 2N HCl 2 steps 76%

TMSO

H

OTMS 31’

H H

H

32

concentrated in vacuo to give crude 31’ as a white solid witch was used in the next step without further purification. To a stirred solution of clude 31’ (2.56 g, 4.58 mmol) in CH2Cl2 (35 mL) was added mCPBA (1.17 g, 4.76 mmol) and NaHCO3 (0.600 g, 7.14 mmol) at 0 ºC and the mixture was stirred for 2 h at room temperature. The mixture was washed with satd aq NaHSO3

and the organic layer was added 2N HCl and stirred for 3 h at room temperature. The mixture was extracted with CH2Cl2 and washed with water and brine, dried (MgSO4) and concentrated in vacuo. The residue was purified by SiO2 column chromatography (hexane/EtOAc = 10:1) to give 32 (1.56 g, 76% from 31) as a white solid. Mp 241–242 °C; [a]²⁰D +7.7 (c 0.65, CHCl3);

IR: nmax 3750 (br), 1733 (s), 1457 (w); ¹H NMR (400 MHz): d 0.78–0.85 (12H, m), 0.90 (3H, d, J = 6.9 Hz), 0.94–2.21 (26H, m), 2.45 (1H, dq J = 12.5, 3.4 Hz), 2.53 (1H, dd, J = 9.0, 19.3 Hz), 3.59 (1H, tt, J = 5.3, 10.7 Hz), 5.14 (1H, dd, J = 8.4, 15.3 Hz), 5.24 (1H, dd, J = 7.7, 15.3 Hz); ¹³C NMR (100 MHz): d 12.1, 14.2, 17.6, 19.6, 19.9, 20.0, 21.3, 25.8, 28.2, 30.3, 31.4, 33.0, 34.6, 35.8, 37.0, 38.0, 39.8, 40.7, 42.8, 44.3, 44.6, 45.8, 46.8, 71.1, 82.6, 133.1, 134.7, 214.6;

HRMS (EI): m/z calcd. for C28H46O3, 430.3447; found, 430.3446 (M⁺).

(3R,4R,7R,E)-3-((2R,4aS,4bS,7S,8aS,10aR)-7-((tert-butyldiphenylsilyl)oxy)-2,4b-dimethyl-1-oxotetradecahydrophenanthren-2-yl)-4,7,8-trimethylnon-5-enoic acid (34)

To a stirred solution of 32 (1.52 g, 3.65 mmol) in DMF (10 mL) and THF (4 mL) was added

Jones reagent, acetone rt, 2 steps 79%

TBDPSO

H

OHO H

H H

33

TBDPSO

O OOH H

H 34 TBDPSCl, Im.

CH₂Cl₂, rt HO

H

OHO H

H H

32

H H

TBDPSCl (1.42 mL, 5.48 mmol) and imidazole (0.745 g, 11.0 mmol) at room temperature and stirred for 3 h at the same temperature. The mixture was quenched with satd aq NH4Cl and extracted with ether. The extract was washed with water and brine, dried (MgSO4) and concentrated in vacuo to give crude 33 as a white solid witch was used in the next step without further purification. To a stirred solution of 33 (2.35 g, 3.52 mmol) in acetone (100 mL) was added Jones reagent (2.65 M, 7.97 mL, 21.1 mmol) at room temperature and the mixture was stirred for 30 min at the same temperature. The mixture was quenched with 2-propanol, diluted with water and concentrated in vacuo to remove acetone. The mixture was extracted with ether, washed with water and brine, dried (MgSO4) and concentrated in vacuo. The residue was purified by SiO2 column chromatography (hexane/EtOAc = 3:1) to give 34 (1.88 g, 76%) as an amorphous solid. [a]²⁰D +6.6 (c 1.00, CHCl3); IR: nmax 3070 (br), 1737 (m), 1704 (s), 1427 (m), 1251 (m); ¹H NMR (400 MHz): d 0.72–1.69 (43H, m), 1.78–1.91 (3H, m), 2.19 (1H, dd, J = 4,3, 16.3 Hz), 2.25– 2.37 (2H, m), 2.41–2.52 (2H, m), 3.57 (1H, tt, J = 5.1, 10.4 Hz), 5.21 (1H, dd, J = 7.6, 15.3 Hz), 5.29 (1H, dd, J = 8.2, 15.3 Hz), 7.33–7.44 (6H, m), 7.65–7.69 (4H, m);

13C NMR (100 MHz): d 11.8, 14.1, 17.4, 19.1, 19.7, 20.0, 20.3, 20.6, 22.0, 22.6, 26.2, 26.9 (3C), 27.5, 31.5, 31.6, 33.0, 34.5, 36.2, 36.7, 37.8, 37.9, 43.1, 43.5, 44.2, 45.1, 51.6, 54.3, 72.4, 127.41, 127.43, 129.41, 129.44, 132.0, 134.6 (2C), 134.7 (2C), 135.0, 135.71, 135.72, 179.3, 218.0;

HRMS (EI): m/z calcd. for C44H64O4Si, 684.4574; found, 684.4576 (M⁺).

(3S,5S,8R,9S,10S,13R,17R)-17-((2R,5R,E)-5,6-dimethylhept-3-en-2-yl)-10,13-dimethyl-2,3,4,5,6,7,8,9,10,11,12,13,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate (38)

To a stirred solution of 29 (1.63 g, 3.47 mmol) in a mixed solvent of MeOH (180 mL) and CH2Cl2 (44 mL) were added dropwise a solution of concentrated H2SO4 (1.84 mL, 35 mmol)

AcO

H

OH O

Zn (60 eq.) H₂SO₄ MeOH/CH₂Cl₂

rt, 63%

H 29

AcO

H

H H

H

38

in MeOH (36.5 mL) over a period of 1 h, during which activated zinc powder (13.6 g, 208 mmol) was also added portionwise. The mixture was quenched with solid NaHCO3 and filtered through a pad of Celite. The filtrate was extracted with CH2Cl2 and the extract was washed with water and brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc = 20:1) to give 38 (0.948 g, 63%) as a white solid.

Mp 107–109 ºC; [a]²⁰D –19.2 (c 4.81, CHCl3); IR: nmax 1735 (s), 1245 (s), 1029 (m); ¹H NMR (400 MHz): d 0.69 (1H, dt, J = 2.7, 11.5 Hz), 0.80–0.86 (9H, m), 0.89–0.94 (6H, m), 0.96–1.05 (4H, m), 1.10–1.66 (12H, m), 1.74–1.92 (5H, m), 1.93–2.05 (5H, m), 2.10–2.25 (2H, m), 4.68 (1H, tt, J = 4.9, 11.4 Hz), 5.12 (1H, br s), 5.18 (1H, dd, J = 7.5, 15.3 Hz), 5.24 (1H, dd, J = 7.0, 15.2 Hz); ¹³C NMR (100 MHz): d 11.9, 16.9, 17.6, 19.6, 19.9, 21.0, 21.4, 21.8, 27.3, 28.2, 29.9, 33.0, 33.9, 34.9, 35.6, 36.4, 36.7, 38.8, 42.3, 42.8, 44.0, 46.8, 53.4, 58.5, 73.6, 117.5, 131.9, 135.5, 155.0, 170.6; HRMS (ESI-TOF): m/z calcd for C30H48O2Na, 463.3552; found, 463.3547 ([M+Na]⁺).

(1R,3bR,5aS,7S,9aS,9bS,11aR)-1-((2R,5R,E)-5,6-dimethylhept-3-en-2-yl)-9a,11a-dimethylhexadecahydronaphtho[1',2':6,7]indeno[1,7a-b]oxiren-7-yl acetate (39)

To a stirred solution of 38 (4.83 g, 11.0 mmol) in EtOH/CH2Cl2 (10:3, 130 mL) was added MMPP·6H2O (6.50 g, 13.1 mmol) in portions at room temperature and the mixture was stirred at the same temperature for 2 h. The mixture was quenched with satd aq Na2S2O3, stirred for an additional 1 h, and concentrated in vacuo. The residue was diluted with water and extracted with CH2Cl2. The extract was successively washed with satd aq NaHCO3 and brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc = 10:1) to give 39 (4.11 g, 82%) as a white solid. Mp 131–133 ºC; [a]²⁰D –6.7 (c 0.55, CHCl3); IR: nmax 1735 (m), 1460 (w), 1364 (w), 1244 (w); ¹H NMR

AcO

H

H H

H

38

AcO

H

H H

H

39 O MMPP

EtOH/CH₂Cl₂ rt, 82%

(400 MHz): d 0.80–0.84 (6H, m), 0.85 (3H, s), 0.86 (3H, s), 0.91 (3H, d, J = 6.8 Hz), 0.94 (3H, d, J = 6.6 Hz), 0.98–1.64 (16H, m), 1.73–2.00 (6H, m), 2.00–2.17 (4H, m), 3.28 (1H, s), 4.68 (1H, tt, J = 4.9, 11.3 Hz), 5.11 (1H, dd, J = 8.2, 15.3 Hz), 5.20 (1H, dd, J = 7.4, 15.3 Hz); ¹³C NMR (100 MHz): d 12.0, 14.7, 17.6, 19.6, 19.9, 20.9, 21.0, 21.4, 25.3, 27.4, 27.7, 32.0, 33.00, 33.03, 33.9, 35.5 (2C), 36.5, 38.7, 40.8, 42.7, 43.6, 48.4, 50.0, 58.1, 73.6, 73.9, 132.2, 135.1, 170.6; HRMS (ESI-TOF): m/z calcd for C30H49O3, 457.3682; found, 457.3693 ([M+H]⁺).

(3R,4R,7R,E)-3-[(2R,4aS,4bS,7S,8aS,10aR)-7-acetoxy-2,4b-dimethyl-1-oxotetradecahydrophenanthren-2-yl]-4,7,8-trimethylnon-5-enoic acid (35).

To a stirred solution of 39 (1.04 g, 2.28 mmol) in acetone (32 mL) was added dropwise the Jones reagent (2.65 M, 3.70 mL, 9.81 mmol) at room temperature. After 30 min of stirring at the same temperature, the mixture was quenched with 2-propanol, diluted with water, and concentrated in vacuo to some extent. The residue was extracted with ether and the extract was washed with brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc = 5:1) to give 35 (0.860 g, 77%) as a white amorphous solid. [a]²⁰D –3.3 (c 3.20, CHCl3); IR: nmax 1733 (vs), 1706 (s), 1246 (s); ¹H NMR (400 MHz): d 0.81 (3H, d, J = 6.8 Hz), 0.83 (3H, d, J = 6.8 Hz), 0.89 (3H, s), 0.92 (3H, d, J = 6.8 Hz), 1.01 (3H, d, J = 6.9 Hz), 1.03–1.94 (22H, m), 2.02 (3H, s), 2.22 (1H, dd, J = 4.6, 16.4 Hz), 2.31–2.40 (2H, m), 2.47–2.56 (2H, m), 4.68 (1H, tt, J = 4.9, 11.4 Hz), 5.24 (1H, dd, J = 7.6, 15.4 Hz), 5.32 (1H, dd, J = 8.1, 15.4 Hz); ¹³C NMR (100 MHz): d 11.6, 17.4, 19.6, 20.0, 20.3, 20.9, 21.3, 22.0, 26.2, 27.3, 27.4, 32.8, 33.0, 33.6, 34.2, 36.2, 36.4, 37.9, 43.1, 43.4, 44.2, 45.1, 51.6, 54.0, 73.2, 132.1, 135.0, 170.6, 179.3, 217.4; HRMS (EI): m/z calcd for C30H48O5, 488.3502; found, 488.3504 (M⁺).

AcO

O OOH H H

H H 35 Jones reagent

acetone, rt AcO 77%

H

H H

H

39 O

(3S,5S,9R,10S,13R,14R,17R)-17-[(2R,5R,E)-5,6-dimethylhept-3-en-2-yl]-10,13-dimethyl-2,3,4,5,6,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate (42).

To a stirred solution of 41 (24.6 g, 61.8 mmol) in pyridine (150 mL) was added AcCl (6.0 mL, 84 mmol) at room temperature. After 2 h of stirring, the mixture was diluted with satd aq NH4Cl and extracted with CHCl3. The extract was washed with brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc = 5:1) to give 42 (26.7 g, 98%) as a white solid. Mp 180–182 ºC; [a]²⁰D –20.2 (c 3.05, CHCl3); IR:

nmax 1732 (s), 1249 (s), 757 (s); ¹H NMR (400 MHz): d 0.54 (3H, s), 0.79–0.86 (9H, m), 0.91 (3H, d, J = 6.8 Hz), 1.02 (3H, d, J = 6.4 Hz), 1.13 (1H, dt, J = 3.6, 13.6 Hz), 1.19–1.90 (20H, m), 1.95–2.06 (5H, m), 4.69 (1H, tt, J = 4.5, 11.1 Hz), 5.11–5.25 (3H, m); ¹³C NMR (100 MHz):

d 12.0, 12.9, 17.6, 19.6, 19.9, 21.1, 21.4 (2C), 22.8, 27.4, 28.1, 29.4, 33.0, 33.7, 34.1, 36.8, 39.3, 39.9, 40.5, 42.7, 43.2, 49.2, 55.0, 55.8, 73.3, 117.2, 131.8, 135.6, 139.4, 170.5; HRMS (EI):

m/z calcd for C30H48O2, 440.3654; found, 440.3651 (M⁺).

(3S,5S,8R,9S,10S,13R,17R)-17-[(2R,5R,E)-5,6-dimethylhept-3-en-2-yl]-10,13-dimethyl-2,3,4,5,6,7,8,9,10,11,12,13,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate (38).

HO

H

41 ^AcO

AcCl, pyridine H rt, 98%

H 42

H H H

H

Gaseous hydrogen chloride [generated by mixing concd HCl (6 mL) and concd H2SO4 (6 mL)]

was bubbled into a solution of 42 (0.500 g, 1.13 mmol) in CH2Cl2 (100 mL) for 15 min at –78 ºC. After 2 h of stirring at the same temperature, the solution was gradually warmed to room temperature over 1 h. The solution was washed with satd aq NaHCO3, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography [Kanto Kagaku silica gel 60N (40–50 µm) impregnated with 9% AgNO3, hexane/EtOAc = 40:1] to give 38 (0.355 g, 71%) together with 43 (0.140 g, 28%), each as a white solid. The minor isomer 43 was re-exposed to the same isomerization conditions to give an additional amount of 38 (0.070 g, 14%). Mp 107–109 ºC; [a]²⁰D –19.2 (c 4.81, CHCl3); IR: nmax 1735 (s), 1245 (s), 1029 (m); ¹H NMR (400 MHz): d 0.69 (1H, dt, J = 2.7, 11.5 Hz), 0.80–0.86 (9H, m), 0.89–0.94 (6H, m), 0.96–1.05 (4H, m), 1.10–1.66 (12H, m), 1.74–1.92 (5H, m), 1.93–2.05 (5H, m), 2.10–2.25 (2H, m), 4.68 (1H, tt, J = 4.9, 11.4 Hz), 5.12 (1H, br s), 5.18 (1H, dd, J = 7.5, 15.3 Hz), 5.24 (1H, dd, J = 7.0, 15.2 Hz); ¹³C NMR (100 MHz): d 11.9, 16.9, 17.6, 19.6, 19.9, 21.0, 21.4, 21.8, 27.3, 28.2, 29.9, 33.0, 33.9, 34.9, 35.6, 36.4, 36.7, 38.8, 42.3, 42.8, 44.0, 46.8, 53.4, 58.5, 73.6, 117.5, 131.9, 135.5, 155.0, 170.6; HRMS (ESI-TOF): m/z calcd for C30H48O2Na, 463.3552;

found, 463.3547 ([M+Na]⁺).

(2S,4aS,4bS,7R,8aR,10aS)-4a,7-dimethyl-8-oxo-7-[(3R,4R,7R,E)-4,7,8-trimethyl-1-oxo-1-(phenylselanyl)non-5-en-3-yl]tetradecahydrophenanthren-2-yl acetate (44).

AcO

H

42

HCl (gas) CH₂Cl₂ –78 ºC to rt H

H AcO

H

38 (71%+14%) H

H H

AcO

H

43 (28%) H

+ H

HCl (gas), CH₂Cl₂ –78 ºC to rt, 50%

To a stirred solution of 35 (5.25 g, 10.7 mmol) in CH2Cl2 (60 mL) was added dropwise a solution of Et3N (1.62 mL, 11.6 mmol) in CH2Cl2 (20 mL) at room temperature. After 20 min of stirring, the mixture was concentrated in vacuo to give the triethylammonium salt of 35 as a brown oil. In another flask, nBu3P (5.30 mL, 21.2 mmol) was added dropwise to a stirred solution of PhSeCl (4.12g, 21.5 mmol) in THF (100 mL) at room temperature and the mixture was stirred for 20 min. To the resulting mixture was added the triethylammonium salt obtained above in THF (80 mL). After 2 h of stirring, the mixture was quenched with 2 M NaOH and extracted with ether. The extract was successively washed with water and brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc = 10:1) to give 44 (6.31 g, 94%) as a white amorphous solid.

[a]²⁰D –17.0 (c 0.87, CHCl3); IR: nmax 1731 (vs), 1698 (s), 1457 (w), 1245 (w); ¹H NMR (600 MHz): d 0.82 (3H, d, J = 6.8 Hz), 0.85 (3H, d, J = 6.7 Hz), 0.87 (3H, s), 0.94 (3H, d, J = 6.8 Hz), 0.99 (3H, d, J = 7.0 Hz), 1.01–1.15 (6H, m), 1.17–1.40 (4H, m), 1.45–1.59 (3H, m), 1.60–

1.66 (1H, m), 1.70–1.77 (3H, m), 1.80 (1H, dt, J = 13.3, 3.5 Hz), 1.82–1.88 (1H, m), 1.90 (1H, q, J = 6.8 Hz), 1.92–1.97 (1H, m), 2.02 (3H, s), 2.27–2.34 (1H, m), 2.46 (1H, dt, J = 4.0, 12.0 Hz), 2.64–2.71 (2H, m), 2.73–2.80 (1H, m), 4.68 (1H, tt, J = 5.0, 11,4 Hz), 5.23 (1H, dd, J = 7.8, 15.4 Hz), 5.30 (1H, dd, J = 8.3, 15.4 Hz), 7.34–7.38 (3H, m), 7.49–7.52 (2H, m); ¹³C NMR (150 MHz): d 11.7, 17.5, 19.7 (2C), 20.0, 20.3, 21.4, 22.2, 22.5, 26.3, 27.3, 27.5, 33.1, 33.6, 36.1, 36.5, 38.3, 43.1, 43.4, 44.5, 45.2, 46.5, 51.5, 53.5, 73.2, 126.8, 128.6, 129.2 (2C), 132.5, 135.1, 135.8 (2C), 170.6, 200.3, 215.6; HRMS (EI): m/z calcd for C36H52O4Se, 628.3031; found, 628.3031 (M⁺).

(2S,4aS,4bS,7R,8aR,10aS)-7-{(1R,2S,3R)-3-[(S)-2,3-dimethylbutyl]-2-methyl-4-oxocyclopentyl}-4a,7-dimethyl-8-oxotetradecahydrophenanthren-2-yl acetate (45)

AcO

O OOH H

PhSeCl Bu₃P, Et₃N THF, rt, 93%

H 35 H

H

O

OSePh H H

44 AcO H

H

To a stirred solution of 44 (4.13 g, 6.58 mmol) in benzene (480 mL) were successively added tributyltin hydride (3.44 mL, 12.8 mmol) and AIBN (0.108 g, 0.656 mmol) at 80 ºC. After 3 h of stirring at the same temperature, the mixture was concentrated in vacuo and the residue was purified by column chromatography [SiO2 containing K2CO3 (10 wt. %), hexane/EtOAc = 20:1]

to give 45 (2.01 g, 65%) as a white solid. Mp 132–134 ºC; [a]²⁰D –65.6 (c 1.22, CHCl3); IR:

nmax 1735 (s), 1701 (m), 1247 (s); ¹H NMR (600 MHz): d 0.81 (6H, d, J = 6.7 Hz), 0.87 (3H, d, J = 6.8 Hz), 0.90 (3H, s), 1.03–1.16 (9H, m), 1.17–1.40 (6H, m), 1.48–1.67 (6H, m), 1.70–1.94 (7H, m), 1.97 (1H, dd, J = 8.2, 18.5 Hz), 2.03 (3H, s), 2,21 (1H, q, J = 8.5 Hz), 2.46 (1H, dt, J

= 3.9, 11.9 Hz), 2.51 (1H, ddd, J = 1.4, 9.8, 18.4 Hz), 4.68 (1H, tt, J = 4.9, 11.4 Hz); ¹³C NMR (150 MHz): d 11.7, 15.0, 17.6, 20.1, 20.2, 21.4, 22.3, 22.4, 26.2, 27.3, 27.4, 31.9, 33.6, 34.1, 34.5, 36.2, 36.3, 36.5, 39.6, 40.6, 43.4, 45.4, 46.8, 50.1, 54.1, 54.6, 73.2, 170.6, 215.4, 219.9;

HRMS (EI): m/z calcd for C30H48O4, 472.3553; found, 472.3553 (M⁺).

(2S,4aS,4bS,7R,8aS,10aS)-7-[(2R,3S,4R)-4-(2,3-dimethylbutyl)-3-methyl-6,10-dithiaspiro[4.5]decan-2-yl]-4a,7-dimethyl-8-oxotetradecahydrophenanthren-2-yl acetate (46).

AcO

O H

O

H H

H

45 O

OSePh H H

44 AcO H

H

Bu₃SnH, AIBN benzene 80 ºC, 65%

To a stirred solution of 45 (1.21 g, 2.56 mmol) in CH2Cl2 (30 mL) were successively added 1,3-propanedithiol (0.643 mL, 6.40 mmol) and BF3·OEt2 (0.205 mL, 1.66 mmol) at –40 ºC.

The mixture was gradually warmed to –20 ºC over 1 h, and the stirring was continued for 5 h.

The mixture was quenched with 2 M NaOH and extracted with CH2Cl2. The extract was washed with water and brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (CH2Cl2/hexane = 5:1) to give 46 (1.35 g, 94%) as a white solid. Mp 79–81 ºC; [a]²⁰D –66.1 (c 0.53, CHCl3); IR: nmax 1731 (s), 1701 (m), 1247 (s), 734 (w);¹H NMR (400 MHz): d 0.86–0.89 (9H, m), 0.90 (3H, s), 1.00–2.10 (34H, m), 2.34 (1H, dt, J = 8.1, 10.6 Hz), 2.52 (1H, dt, J = 3.9, 11.9 Hz), 2.66–2.76 (2H, m), 2.85–3.00 (2H, m), 3.13 (1H, ddd, J = 3.0, 11.2, 14.2 Hz), 4.68 (1H, tt, J = 4.9, 11.3 Hz); ¹³C NMR (150 MHz): d 11.8, 15.5, 18.5, 19.5, 19.8, 20.4, 21.4, 24.0, 26.0, 26.2, 27.3, 27.4, 27.6, 28.1, 32.8, 33.7 , 35.0, 35.9, 36.3, 36.5, 37.1, 40.0, 42.4, 43.5, 45.2, 49.6, 50.4, 54.8, 55.0, 59.4, 73.2, 170.6, 216.3; HRMS (EI): m/z calcd for C33H54O3S2, 562.3514; found, 562.3515 (M⁺). When this thioacetalization was conducted at room temperature for 2 h [45 (2.28 g, 4.82 mmol), 1,3-propaneditiol (0.910 mL, 9.10 mmol), BF3·OEt2 (0.590 mL, 4.69 mmol), CH2Cl2 (60 mL)], a ca. 2:1 mixture of 46 and 22-epi-46 was obtained. The two epimers were separated by silica gel column chromatography (CH2Cl2/hexane = 5:1) to give 46 (1.63 g, 60%) and 22-epi-46 (0.84 g, 31%).

Physicochemical properties of 22-epi-46: Mp 78–80 ºC; [a]²⁰D –2.4 (c 0.42, CHCl3); IR: nmax

1732 (s), 1701 (m), 1248 (s); ¹H NMR (400 MHz): d 0.81 (3H, d, J = 6.7 Hz), 0.82 (3H, d, J =

AcO

O O

H 45 H

H H

AcO

O H 46

H

H H S S

AcO

O H

H

H H S HS SH S

HS SH

BF₃•OEt₂ CH₂Cl₂ –40 to –20 ºC

95%, 5 h

22-epi-46 (31%)

22

BF₃•OEt₂

+

CH₂Cl₂ rt, 2 h

46 (60%)

6.8 Hz), 0.84–0.93 (9H, m), 0.94–1.17 (9H, m), 1.18–1.89 (18H, m), 1.94–2.11 (5H, m), 2.52 (1H, dt, J = 3.7, 11.8 Hz), 2.60–2.73 (2H, m), 3.07–3.21 (3H, m), 4.68 (1H, tt, J = 4.9, 11.3 Hz); ¹³C NMR (150 MHz): d 11.8, 15.1, 15.6, 20.4, 20.6, 21.4, 21.5, 25.7, 26.0, 26.9, 27.3, 27.4, 28.4, 29.0, 30.5, 33.7 (2C), 36.10, 36.12, 36.3, 36.6, 37.2, 43.5, 43.9, 45.3, 50.5, 51.0, 55.0 (2C), 61.1, 73.2, 170.6, 216.2; HRMS (EI): m/z calcd for C33H54O3S2, 562.3514; found, 562.3515 (M⁺).

(2S,4aS,4bS,7R,8aS,10aS)-7-{(1R,2R,3R)-3-[(S)-2,3-dimethylbutyl]-2-methylcyclopentyl}-4a,7-dimethyl-8-oxotetradecahydrophenanthren-2-yl acetate (47) and its C22-epimer (22-epi-47).

To a stirred solution of 46 (0.135 g, 0.240 mmol) in THF (0.5 mL) was added a suspension of Raney Ni [prepared by washing 2 g of “skeletal nickel catalyst slurry in water” (Tokyo Chemical Industry Co., LTD.) with absolute EtOH several times and suspending the residual solid in 3 mL of absolute EtOH] at room temperature. The mixture was stirred at 50 ºC for 1 day under a hydrogen atmosphere. The supernatant solution was transfered to a separatory funnel by using water and EtOAc, and the resulting mixture was extracted with EtOAc. The extract was successively washed with water and brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc = 15:1) to give 47 (0.073 g, 66%) as a white solid. In the same manner, 22-epi-346 (0.055 g, 0.098 mmol) gave 22-epi-47 (0.029 g, 65%) as a white solid. physicochemical properties of 47: Mp 118–120 ºC; [a]²⁰D –26.9 (c 0.76, CHCl3); IR: nmax 1734 (m), 1702 (m), 1244 (s); ¹H NMR (400 MHz): d 0.74 (3H, d, J = 7.2 Hz), 0.77 (3H, d, J = 6.8 Hz), 0.86 (3H, d, J = 6.8 Hz), 0.90 (3H,

O

46 (22β) 22-epi-46 (22α) H

H

H H S

22 S

O H

H H H H₂, Raney-Ni

EtOH, THF rt

47 (22β) 22-epi-47 (22α) 66% for 47

65% for 22-epi-47

AcO AcO

s), 0.94 (3H, d, J = 6.4 Hz), 0.97–1.95 (30H, m), 2.03 (3H, s), 2.51 (1H, dt, J = 3.7, 11.6 Hz), 4.68 (1H, tt, J = 5.0, 11.6 Hz); ¹³C NMR (100 MHz): d 11.7, 15.5, 16.1, 19.5, 20.3, 20.8, 21.3, 21.4, 26.1, 27.3, 27.4, 28.3, 29.9, 32.6, 33.6, 36.2, 36.3, 36.5, 36.7, 39.6, 41.6, 43.4, 45.2, 46.7, 51.1, 51.8, 54.7, 73.2, 170.5, 216.8; HRMS (EI): m/z calcd for C30H50O3, 458.3760; found, 458.3759 (M⁺). Physicochemical properties of 22-epi-47: Mp 115–117 ºC; [a]²⁰D –28.0 (c 1.50, CHCl3); IR: nmax 1734 (s), 1704 (m), 1246 (s); ¹H NMR (400 MHz): d 0.77 (3H, d, J = 6.8 Hz), 0.79 (3H, d, J = 7.0 Hz), 0.85 (3H, d, J = 6.8 Hz), 0.87 (3H, d, J = 7.2 Hz), 0.89 (3H, s), 0.99–

1.41 (15H, m), 1.42–1.97 (15H, m), 2.03 (3H, s), 2.46 (1H, dt, J = 4.0, 11.8 Hz), 4.68 (1H, tt, J

= 4.9, 11.4 Hz); ¹³C NMR (100 MHz): d 11.7, 15.3, 17.6, 17.8, 20.2, 20.4, 21.4, 22.0, 26.2, 26.6, 27.3, 27.5, 30.0, 32.5, 33.7, 33.8, 34.6, 36.2, 36.5, 37.0, 38.2, 41.3, 43.5, 45.3, 51.2, 53.2, 54.1, 73.3, 170.6, 216.7; HRMS (ESI-TOF): m/z calcd for C30H51O3, 459.3838; found, 459.3838 ([M+H]⁺).

(2S,4aS,4bS,7R,8aS,10aS)-7-{(1R,2S)-3-[(S)-2,3-dimethylbutyl]-4-(ethylthio)-2-methylcyclopent-3-en-1-yl}-4a,7-dimethyl-8-oxotetradecahydrophenanthren-2-yl acetate (45’).

To a stirred solution of 45 (2.42 g, 5.12 mmol) in CH2Cl2 (16.9 mL) were added successively EtSH (1.48 mL, 20.0 mmol) and TMSCl (1.91 mL, 15.0 mmol) at room temperature. After 6 h of stirring, the mixture was diluted with satd aq NaHCO3 and extracted with ether. The extract was washed with brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc = 15:1) to give 45‘ (2.33 g, 88%) as a colorless viscous oil. [a]²⁰D –27.2 (c 2.75, CHCl3); IR: nmax 1733 (s), 1702 (m), 1245 (s), 758 (w); ¹H NMR (400 MHz): d 0.80 (6H, d, J = 6.8 Hz), 0.85 (3H, d, J = 6.8 Hz), 0.90 (3H, s),

AcO

O O

H 45 H

H H

AcO

O H 45’

H H EtSH, TMSCl H

CH₂Cl₂ rt, 88%

SEt

0.98–1.89 (28H, m), 2.03 (3H, s), 2.12–2.22 (2H, m), 2.25–2.34 (1H, m), 2.39 (1H, dd, J = 9.0, 13.8 Hz), 2.49 (1H, dt, J = 3.6, 11.7 Hz), 2.64 (2H, q, J = 7.2 Hz), 2.78–2.90 (1H, m), 4.68 (1H, tt, J = 4.6, 11.6 Hz); ¹³C NMR (100 MHz): d 11.7, 15.0, 15.4, 16.1, 19.4, 20.3, 21.0, 21.2, 21.4, 25.0, 25.9, 27.26, 27.33, 29.7, 32.4, 33.6, 34.4, 36.1, 36.3, 36.4, 37.3, 43.3, 44.8, 45.3, 48.8, 51.6, 54.6, 73.1, 127.0, 145.7, 170.5, 216.7; HRMS (ESI-TOF): m/z calcd for C32H53O3S, 517.3715; found, 517.3706 ([M+H]⁺).

(2S,4aS,4bS,7R,8aS,10aS)-7-{(1R,2S)-3-[(S)-2,3-dimethylbutyl]-2-methylcyclopent-3-en-1-yl}-4a,7-dimethyl-8-oxotetradecahydrophenanthren-2-yl acetate (48).

A suspension of Raney Nickel in EtOH [prepared by washing 3.08 g of “skeletal nickel catalyst slurry in water” (Tokyo Chemical Industry Co., LTD.) with absolute EtOH several times and suspending the residual solid in 9 mL of absolute EtOH] was added to 45‘ (0.165 g, 0.319 mmol) at room temperature. The mixture was stirred at 60 ºC for 6 h while adding additional Raney nickel (the same suspension as prepared above ´ 3) at intervals of 1 h. The supernatant solution was transfered to an eggplant flask with water and EtOAc and concentrated in vacuo. The residue was diluted with water and extracted with EtOAc. The extract was washed with brine, dried (MgSO4), filtered through a pad of Celite, and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc = 20:1) to give 48 (0.121 g, 83%) as a white solid. Mp 107–109 ºC; [a]²⁰D –39.9 (c 1.01, CHCl3); IR: nmax 1733 (s), 1704 (m), 1245 (s); ¹H NMR (400 MHz): d 0.75 (3H, d, J = 7.2 Hz), 0.78 (3H, d, J = 6.8 Hz), 0.86 (3H, d, J = 6.8 Hz), 0.89 (3H, s), 0.98–1.28 (9H, m), 1.29–1.89 (16H, m), 1.90–2.08 (5H, m), 2.09–2.21 (2H, m), 2.46 (1H, dt, J = 3.6, 11.7 Hz), 2.52–2.63 (1H, m), 4.68 (1H, tt, J

= 4.8, 11.4 Hz), 5.17 (1H, s); ¹³C NMR (100 MHz): d 11.8, 15.1, 16.3, 20.0, 20.4, 20.9, 21.1,

AcO

O H 45’

H H H

AcO

O H 48

H H H H₂, Raney-Ni

EtOH 50 ºC, 83%

SEt

21.4, 26.0, 27.3, 27.4, 30.2, 33.6, 33.7, 34.1, 34.2, 36.2 (2C), 36.5, 43.4, 44.9, 45.4, 50.9, 51.6, 54.5, 73.3, 123.0, 146.9, 170.6, 216.9; HRMS (ESI-TOF): m/z calcd for C30H49O3, 457.3682;

found, 457.3693 ([M+H]⁺).

(2S,4aS,4bS,7R,8aR,10aS)-7-{(1R,2R,3R)-3-[(S)-2,3-dimethylbutyl]-2-methylcyclopentyl}-4a,7-dimethyl-8-oxotetradecahydrophenanthren-2-yl acetate (47) and its C22-epimer (22-epi-47).

A mixture of 48 (24.0 mg, 52.5 µmol) and 10% Pd/C (0.012 g) in hexane (1.0 mL) was stirred at room temperature for 12 h under a hydrogen atmosphere. The mixture was filtered through a pad of Celite, and the filtrate was concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc = 20:1) to give 23.0 mg of 47 (95%) as a white solid, the physicochemical data of which were identical with those of a product obtained by desulfurization of 46.

A mixture of 48 (104 mg, 0.228 mmol) and Crabtree’s catalyst (12.8 mg, 0.016 mmol) in CH2Cl2 (2.5 mL) was stirred at room temperature for 18 h under a hydrogen atmosphere. The mixture was concentrated in vacuo, diluted with Et2O, and filtered throuogh a pad of Celite.

The filtrate was concentrated in vacuo, and the residue was purified by silica gel column chromatography [Kanto Kagaku silica gel 60N (40–50 µm), hexane/CH2Cl2 = 4:1] to give 47

AcO

O H

H

AcO

O H

H 47

22-epi-47 (58%) H

H H

+

H AcO

O H 48

H

H H H₂, Pd/C

hexane rt, 95%

H₂ Crabtree’s cat.

CH₂Cl₂, rt 47 (34%)

(36.0 mg, 34%) as a white solid and 22-epi-47 (61.0 mg, 58%) as a white solid. The physicochemical data of 47 and 22-epi-47 were identical with those of products obtained by desulfurization of 46 and 22-epi-46, respectively.

(2S,4aS,7R,10aS)-7-{(1R,2R,3R)-3-[(S)-2,3-dimethylbutyl]-2-methylcyclopentyl}-4a,7-dimethyl-8-oxo-1,2,3,4,4a,5,6,7,8,9,10,10a-dodecahydrophenanthren-2-yl acetate (50).

To a stirred solution of 47 (0.902 g, 1.97 mmol) in THF (20 mL) was added trimethylphenylammonium tribromide (1.48 g, 3.94 mmol) in portions at 50 ºC. After 2 h of stirring at the same temperature, DBU (0.295 mL, 1.97 mmol) was added. The resulting mixture was stirred for 1 h, diluted with water, and then extracted with ether. The extract was successively washed with water and brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc = 20:1) to give 50 (0.796 g, 89%) as a white amorphous solid. [a]²⁰D +116.6 (c 0.76, CHCl3); IR: nmax 1732 (vs), 1660 (s), 1625 (m), 1244 (s); ¹H NMR (400 MHz): d 0.75 (3H, d, J = 6.8 Hz), 0.77 (3H, d, J = 7.2 Hz), 0.83–0.93 (4H, m), 0.95 (3H, s), 0.99–1.12 (7H, m), 1.22–2.06 (24H, m), 2.21 (1H, br d, J = 17.2 Hz), 2.40–2.58 (2H, m), 4.75 Hz, (1H, tt, J = 4.6, 11.0 Hz); ¹³C NMR (100 MHz):

d 15.5, 16.4, 17.3, 19.4, 20.8, 21.0, 21.4, 22.1, 23.3, 24.4, 26.6, 27.1, 30.1, 31.9, 32.5, 33.4, 33.7, 36.5, 37.6, 39.6, 39.9, 41.4, 45.5, 46.4, 48.0, 72.9, 129.3, 160.4, 170.6, 204.6; HRMS (EI):

m/z calcd for C30H48O3, 456.3603; found, 456.3601 (M⁺).

(2S,4aS,7R,9R,10aR)-9-bromo-7-{(1R,2R,3R)-3-[(S)-2,3-dimethylbutyl]-2- methylcyclopentyl}-4a,7-dimethyl-8-oxo-1,2,3,4,4a,5,6,7,8,9,10,10a-dodecahydrophenanthren-2-yl acetate (54).

AcO

O H 47

H H H

PhNMe₃•Br₃ THF, 50 ºC

then DBU

50 ºC, 89% _AcO

O H 50

H

To a stirred solution of 50 (0.796 g, 1.74 mmol) in CCl4 (150 mL) were successively added DDH (0.274 g, 0.957 mmol) and V-70 (0.107 g, 0.347 mmol) at 40 ºC. After 1.5 h of stirring at the same temperature, the mixture was concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc = 15:1) to give 54 (0.567 g, 61%) as a white solid.

Mp 43–45 ºC; [a]²⁰D +31.4 (c 0.44, CHCl3); IR: nmax 1734 (s), 1673 (m), 1243 (s); ¹H NMR (400 MHz): d 0.76 (3H, d, J = 6.8 Hz), 0.78 (3H, d, J = 6.8 Hz), 0.85–0.93 (5H, m), 0.96 (3H, s), 1.03 (3H, s), 1.08 (3H, d, J = 6.8 Hz), 1.24–2.08 (22H, m), 2.17–2.33 (2H, m), 2.49 (1H, ddd, J = 5.0, 11.1, 19.0 Hz), 4.85 (1H, tt, J = 5.2, 11.2 Hz), 5.44 (1H, br s); ¹³C NMR (100 MHz): d 15.6, 16.3, 17.7, 18.7, 20.8, 21.2, 21.4, 22.5, 26.6, 27.0, 30.0, 32.3, 32.6, 32.7, 32.8, 34.9, 35.4, 36.6, 38.2, 39.5, 41.4, 45.9, 46.3, 46.7 (2C), 72.3, 131.0, 162.5, 170.5, 202.1; HRMS (ESI-TOF): m/z calcd for C30H48BrO3, 535.2787; found, 535.2780 ([M+H]⁺).

(2S,4aS,7R,10aR)-7-{(1R,2R,3R)-3-[(S)-2,3-dimethylbutyl]-2-methylcyclopentyl}-4a,7-dimethyl-8-oxo-1,2,3,4,4a,5,6,7,8,10a-decahydrophenanthren-2-yl acetate (56).

To a stirred solution of PhSeSePh (36.0 mg, 0.115 mmol) in EtOH (0.5 mL) was added NaBH4

AcO

O H

H 50

AcO

O H

H 54 Br DDH, V-70

CCl₄, 40 ºC 61%

AcO

O H

H 54

Br AcO

O H

H 56 PhSeSePh

NaBH₄ THF/EtOH then H₂O₂

rt, 74%

(8.7 mg, 0.23 mmol) at room temperature. After 10 min of stirring, a solution of 54 (62.0 mg, 0.116 mmol) in THF (1.0 mL) was added and the stirring was continued for 1 hour at same temperature. To the mixture was then added 30% H2O2 (39.5 µL, 0.387 mmol). The mixture was stirred for 1 hour, quenched with satd aq Na2S2O3, and extracted with ether. The extract was successively washed water and brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc = 20:1) to give 56 (39.0 mg, 74%) as a white amorphous solid. [a]²⁰D +12.5 (c 0.85, CHCl3); IR: nmax 1735 (s), 1666 (m), 1247 (s); ¹H NMR (600 MHz): d 0.75 (3H, d, J = 6.8 Hz), 0.77 (3H, d, J = 6.8 Hz), 0.86 (3H, d, J = 7.0 Hz), 0.87–0.92 (4H, m), 0.98 (3H, s), 1.01 (3H, d, J = 6.5 Hz), 1.07 (1H, dq, J = 12.6, 8.3 Hz), 1.24–1.53 (7H, m), 1.56–1.76 (5H, m), 1.85 (1H, dt, J = 12.9, 3.3 Hz), 1.92–2.08 (7H, m), 2.23 (1H, dt, J = 19.9, 4.9 Hz), 2.30–2.36 (1H, m), 2.53 (1H, ddd, J = 5.3, 8.9, 19.9 Hz), 4.77 (1H, tt, J = 5.0, 11.3 Hz), 5.50 (1H, dd, J = 2.2, 9.6 Hz), 6.58 (1H, dd, J = 3.2, 9.5 Hz); ¹³C NMR (150 MHz): d 12.3, 15.6 (2C), 16.3, 19.5, 20.8 (2C), 21.38, 21.43, 26.5, 27.1, 30.1, 31.72, 31.73, 32.0, 36.6, 37.6, 39.6, 40.2, 41.6, 45.5, 46.3, 48.6, 72.7, 120.9, 128.1, 129.4, 161.3, 170.6, 201.7; HRMS (EI): m/z calcd for C30H46O3, 454.3447; found, 454.3446 (M⁺).

(2S,4aS,7R,9R,10R,10aS)-7-{(1R,2R,3R)-3-[(S)-2,3-dimethylbutyl]-2-methylcyclopentyl}-

10-iodo-4a,7-dimethyl-8-oxo-9-[(trimethylsilyl)oxy]-1,2,3,4,4a,5,6,7,8,9,10,10a-dodecahydrophenanthren-2-yl acetate (62).

To a stirred solution of 56 (63.0 mg, 0.138 mmol) in acetone (1.0 mL) were successively added NIS (0.062 g, 0.28 mmol) and water (0.15 mL) at 0 ºC. After 2 h of stirring, the mixture was diluted with water and extracted with EtOAc. The extract was successively washed with water and brine, dried (MgSO4), and concentrated in vacuo to give a ca. 5.5:1 mixture of 62‘ and 63’

as a brown amorphous solid (0.083 g), which was then taken up in 2,6-lutidine (0.80 mL). To the solution was added TMSOTf (0.027 mL, 0.15 mmol) at room temperature. After 20 min of stirring, the mixture was quenched with satd aq NH4Cl and extracted with CH2Cl2. The extract was successively washed with water and brine, dried with (MgSO4), and concentrated in vacuo.

The residue was purified by silica gel column chromatography (hexane/EtOAc = 10:1) to give 62 (45.0 mg, 48% from 56) as a white solid together with 63 (9.0 mg, 9.7% from 56) as a white solid. Physicochemical properties of 62: Mp 43–44 ºC; [a]²⁰D +67.9 (c 1.57, CHCl3); IR: nmax

1737 (s), 1666 (m), 1246 (s), 1031 (w); ¹H NMR (400 MHz): d 0.23 (9H, s), 0.75 (3H, d, J = 6.9 Hz), 0.78 (3H, d, J = 6.8 Hz), 0.84–0.94 (5H, m), 0.95–0.99 (6H, m), 1.00–1.14 (2H, m), 1.17 (3H, s), 1.20–1.85 (13H, m), 1.87–2.00 (2H, m), 2.05 (3H, s), 2.20 (1H, dt, J = 18.6, 4.3 Hz), 2.32–2.51 (2H, m), 4.20 (1H, dd, J = 6.7, 13.4 Hz), 4,70 (1H, tt, J = 4.9, 11.4 Hz), 5.14 (1H, dd, J = 1.6, 6.7 Hz); ¹³C NMR (100 MHz): d 1.1 (3C), 15.6, 16.4, 17.0, 20.8, 20.9, 21.0,

AcO

O H

H 56

NIS, H₂O acetone

0 ºC AcO

O H

AcO

O H

OTMS I I

H H OTMS

62’ 63’

+

AcO

O H

AcO

O H

OTMS I I

H H OTMS

62 48%

63 9.7%

+

TMSOTf, 2,6-lut., rt

21.3, 22.5, 26.6, 27.0, 30.2, 31.3, 31.8, 33.9, 36.5, 36.6, 39.7, 40.2, 41.8, 45.3, 45.6, 46.4, 46.8, 49.6, 72.5, 76.5, 132.8, 162.2, 170.4, 201.6; HRMS (EI): m/z calcd for C33H55IO4Si 670.2914;

found, 670.2908 (M⁺). Physicochemical properties of 63: mp 42–44 ºC; Mp 42–44 ºC; [a]²⁰D

+36.4 (c 0.44, CHCl3); IR: nmax 1735 (s), 1671 (m), 1245(s), 1042 (m); ¹H NMR (400 MHz): d 0.15 (9H, s), 0.75 (3H, d, J = 6.8 Hz), 0.77 (3H, d, J = 6.4 Hz), 0.82–0.92 (5H, m), 0.97 (3H, s), 0.99–1.13 (5H, m), 1.24–1.81 (16H, m), 1.94–2.08 (6H, m), 2.22–2.33 (1H, m), 2.53 (1H, ddd, J = 4.9, 10.7, 18.3 Hz), 4.07 (1H, d, J = 1.4 Hz), 4.89–4.99 (1H, m), 5.20 (1H, br s); ¹³C NMR (100 MHz): d 0.4 (3C), 15.6, 16.3, 18.9, 19.5, 20.8, 20.9, 21.4, 22.0, 26.3, 27.0, 30.0, 31.8, 32.3, 34.9, 35.5, 36.6 (2C), 37.6, 38.4, 39.5, 41.4, 46.0, 46.4, 47.1, 70.0, 71.8, 128.5, 160.9, 170.6, 203.1; HRMS (EI): m/z calcd for C33H55IO4Si 670.2914; found, 670.2913 (M⁺).

(3S,4aR,5aS,6R,8R,10bR)-8-{(1R,2R,3R)-3-[(S )-2,3-dimethylbutyl]-2-

methylcyclopentyl}-8,10b-dimethyl-7-oxo-6-[(trimethylsilyl)oxy]-1,3,4,5a,6,7,8,9,10,10b-decahydro-2H-phenanthro[8a,9-b]oxiren-3-yl acetate (67).

To a stirred mixture of 62 (14.5 mg, 21.6 µmol) and NaHCO3 (7.3 mg, 86.6 µmol) in CH2Cl2

(0.7 mL) was added mCPBA (65%, 11.5 g, 43.3 µmol) at room temperature. After 30 min of stirring, the mixture was quenched with satd aq Na2S2O3 and extracted with CH2Cl2. The extract was successively washed with water and brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc = 10:1) to give 67 (9.4 mg 78%) as a white amorphous solid. [a]²⁰D +2.2 (c 0.55 CHCl3); IR: nmax 1739 (s), 1663 (m), 1248 (s), 1072 (w), 883 (w); ¹H NMR (400 MHz): d 0.13 (9H, s), 0.71–0.83 (7H, m), 0.83–

0.93 (4H, m), 0.96 (3H, s), 0.99–1.09 (4H, m), 1.16–1.89 (15H, m), 1.94–2.13 (6H, m), 2.13–

AcO

O H O OTMS

67 mCPBA

NaHCO₃ CH₂Cl₂ rt, 78%

AcO

O H OTMS H I

62

2.23 (1H, m), 2.30 (1H, dd, J = 12.0, 13.0 Hz), 2.40 (1H, ddd, J = 5.1, 10.7, 19.0 Hz), 3.08 (1H, d, J = 3.2 Hz), 4.95 (1H, tt, J = 5.0, 11.4 Hz), 5.06 (1H, d, J = 3.2 Hz); ¹³C NMR (100 MHz):

d 0.5 (3C), 15.6, 16.4, 19.3, 20.8, 21.0, 21.25, 21,26, 22.4, 26.5, 26.6, 29.3, 30.2, 31.9, 32.0, 35.1, 36.6, 39.6, 39.8, 41.4, 45.2, 46.5, 47.5, 60.5, 60.9, 62.1, 70.7, 128.6, 159.5, 170.2, 202.3;

HRMS (EI): m/z calcd for C33H54O5Si, 558.3741; found, 558.3746 (M⁺).

(3S,4aR,5aS,6R,8R,10bR)-8-{(1R,2R,3R)-3-[(S)-2,3-dimethylbutyl]-2-methylcyclopentyl}-

3,6-dihydroxy-8,10b-dimethyl-1,3,4,6,8,9,10,10b-octahydro-2H-phenanthro[8a,9-b]oxiren-7(5aH)-one (strophasterol A).

A solution of KOH (5% in MeOH, 1.1 mL, ca. 0.98 mmol) was added to 67 (9.4 mg, 0.017 mmol) at room temperature and the resulting mixture was stirred for 30 min. The mixture was diluted with water and extracted with EtOAc. The extract was washed with brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (CH2Cl2/MeOH = 10:1) to give strophasterol A (6.0 mg, 80%) as a white solid.

Mp = 99–101 ºC; [a]²⁰D +2.3 (c 0.26 MeOH); IR: nmax 3446 (br), 1654 (s), 1457 (m); ¹H NMR (400 MHz): d 0.75 (3H, d, J = 6.8 Hz), 0.77 (3H, d, J = 6.8 Hz), 0.84–0.92 (4H, m), 0.96 (3H, s), 1.00 (3H, d, J = 6.5 Hz), 1.02–1.11 (1H, m), 1.20–1.78 (16H, m), 1.83–1.95 (2H, m), 1.98–

2.07 (2H, m), 2.17–2.27 (2H, m), 2.35–2.47 (1H, m), 2.83 (1H, d, J = 3.3 Hz), 3.24 (1H, d, J = 2.7 Hz), 3.90–4.03 (1H, m), 4.87 (1H, br s); ¹³C NMR (100 MHz): d 15.6, 16.4, 19.0, 20.77, 20.79, 22.1, 22.3, 26.4, 29.2, 30.2, 30.4, 31.8, 32.2, 36.6, 38.8, 39.58, 38.59, 41.5, 45.6, 46.4, 47.6, 59.4, 62.5, 63.0, 68.3, 128.1, 159.4, 205.5; HRMS (ESI-TOF): m/z calcd for C28H44O4Na, 467.3137; found, 467.3122 ([M+Na]⁺).

AcO

O H

O OTMS HO

O H O OH KOH

MeOH, rt 82%

67 strophasterol A

(2S,4aS,7R,10aS)-7-((1R,2R,3S)-3-((S)-2,3-dimethylbutyl)-2-methylcyclopentyl)-4a,7-dimethyl-8-oxo-1,2,3,4,4a,5,6,7,8,9,10,10a-dodecahydrophenanthren-2-yl acetate (22-epi-50)

In the same manner as described for the preparation of 50, 47 (163 mg) gave 22-epi-50 (138 mg, 85%). [a]²⁰D +73.4 (c 0.24, CHCl3); IR: nmax 1733 (s), 1660 (m); ¹H NMR (400 MHz): d 0.76 (3H, d, J = 6.8 Hz), 0.79 (3H, d, J = 6.8 Hz), 0.82–0.92 (7H, m), 0.95 (3H, s), 1.04 (3H, s), 1.05–1.85 (18H, m), 1.85–2.00 (4H, m), 2.04 (3H, s), 2.23 (1H, br d, J = 18.8 Hz), 2.38–2.56 (2H, m), 4.73 (1H, tt, J = 5.2, 11.3 Hz); ¹³C NMR (100 MHz): d 15.2, 17.4, 17.70, 17.74, 18.7, 20.3, 21.4, 22.1, 23.3, 24.4, 26.4, 27.1, 30.2, 32.36, 32.43, 33.4, 33.7, 34.6, 36.6, 36.9, 37.6, 39.9, 41.4, 45.8, 48.9, 72.9, 129.3, 160.3, 170.6, 204.3; HRMS (EI): m/z calcd for C30H48O3, 456.3603; found, 456.3603 (M⁺).

(2S,4aS,7R,9R,10aR)-9-bromo-7-((1R,2R,3S)-3-((S)-2,3-dimethylbutyl)-2- methylcyclopentyl)-4a,7-dimethyl-8-oxo-1,2,3,4,4a,5,6,7,8,9,10,10a-dodecahydrophenanthren-2-yl acetate (22-epi-53)

In the same manner as described for the preparation of 53, 50 (126 mg) gave 22-epi-53 (75.0 mg, 51%). Mp: 43–44 ºC; [a]²⁰D +28.0 (c 2.00, CHCl3); IR: nmax 1734 (s), 1673 (m), 1457 (w), 1374 (w), 1243 (s); ¹H NMR (400 MHz): d 0.75–0.83 (7H, m), 0.84–0.94 (8H, m), 0.96 (3H, d, J = 7.0 Hz), 1.02–1.36 (8H, m), 1.47–1.74 (7H, m), 1.79–2.02 (6H, m), 2.04 (3H,

AcO

O H

H

22-epi-50

AcO

O H

H

22-epi-53 Br

s), 2.19–2.34 (2H, m), 2.46 (1H, ddd, J = 5.2, 10.7, 18.7 Hz), 4.85 (1H, tt, J = 5.3, 11.3 Hz), 5.44 (1H, br s); ¹³C NMR (100 MHz): d 15.2, 17.7, 17.8, 17.9, 18.3, 20.3, 21.3, 22.6, 26.1, 27.0, 30.3, 32.4, 32.7, 32.78, 32.83, 34.6, 35.0, 35.4, 36.6, 36.9, 38.3, 41.5, 45.8, 46.3, 48.1, 72.3, 131.2, 162.9, 170.4, 201.4; HRMS (ESI-TOF): m/z calcd for C30H48BrO3, 535.2787; found, 535.2780 ([M+H]⁺).

(2S,4aS,7R,10aR)-7-((1R,2R,3S)-3-((S)-2,3-dimethylbutyl)-2-methylcyclopentyl)-4a,7-dimethyl-8-oxo-1,2,3,4,4a,5,6,7,8,10a-decahydrophenanthren-2-yl acetate (22-epi-56)

In the same manner as described for the preparation of 56, 53 (73.0 mg) gave 22-epi-56 (44.0 mg, 71%). [a]²⁰D –4.6 (c 2.25, CHCl3); IR: nmax 1735 (s), 1667 (m), 1468 (w), 1377 (w), 1245 (s); ¹H NMR (400 MHz): d 0.76 (3H, d, J = 6.7 Hz), 0.79 (3H, d, J = 6.9 Hz), 0.84–

0.91 (10H, m), 0.97 (3H, s), 0.99–1.36 (5H, m), 1.37–1.89 (9H, m), 1.92–2.10 (7H, m), 2.26 (1H, dt, J = 20.0, 5.3 Hz), 2.33 (1H, br dd, J = 2.6, 13.8 Hz), 2.53 (1H, ddd, J = 5.7, 7.9, 19.9 Hz), 4.77 (1H, tt, J = 4.9, 11.2 Hz), 5.49 (1H, dd, J = 2.1, 9.5 Hz), 6.57 (1H, dd, J = 3.1, 9.6 Hz); ¹³C NMR (100 MHz): d 12.4, 15.2, 17.7, 17.8, 19.0, 20.2, 21.3, 21.4, 26.1, 27.1, 30.2, 31.2, 31.7, 32.1, 32.4, 34.6, 36.9, 37.0, 37.6, 40.2, 41.4, 45.9, 49.7, 72.7, 121.0, 128.1, 129.4, 161.2, 170.5, 201.4; HRMS (EI): m/z calcd for C30H46O3, 454.3447; found, 454.3444 (M⁺).

(2S,4aS,7R,9R,10R,10aS)-7-((1R,2R,3S)-3-((S)-2,3-dimethylbutyl)-2-methylcyclopentyl)-

10-iodo-4a,7-dimethyl-8-oxo-9-((trimethylsilyl)oxy)-1,2,3,4,4a,5,6,7,8,9,10,10a-dodecahydrophenanthren-2-yl acetate (22-epi-62)

AcO

O H

H

22-epi-56

In the same manner as described for the preparation of 62, 22-epi-56 (56.0 mg) gave 39.0 mg (47%) of 22-epi-62 and 8.0 mg (9.7%) of 22-epi-63. Physicochemical properties of 22-epi-62:

mp: 44–46 ºC; [a]²⁰D +30.9 (c 0.23, CHCl3); IR: nmax 1737 (s), 1668 (m), 1451 (w), 1373 (w), 1246 (s); ¹H NMR (400 MHz): d 0.22 (9H, s), 0.76 (3H, d, J = 6.7 Hz), 0.79 (3H, d, J = 6.8 Hz), 0.83 (3H, d, J = 6.8 Hz), 0.86 (3H, d, J = 6.8 Hz), 0.97 (3H, s), 1.02–1.85 (20H, m), 1.87–

1.98 (2H, m), 2.06 (3H, s), 2.23 (1H, dt, J = 19.1, 4.7 Hz), 2.31–2.40 (1H, m), 2.40–2.51 (1H, m), 4.20 (1H, dd, J = 6.7, 13.0 Hz), 4,70 (1H, tt, J = 4.9, 11.4 Hz), 5.14 (1H, br dd, J = 1.2, 6.5 Hz); ¹³C NMR (100 MHz): d 1.1 (3C), 15.2, 17.2, 17.6, 17.7, 19.7, 20.3, 21.4, 22.2, 26.5, 27.0, 30.2, 31.3, 32.2, 34.0, 34.5, 36.4, 36.8, 36.9, 40.1, 41.3, 45.67, 45.70, 46.7, 50.1, 72.4, 76.4, 132.7, 161.7, 170.5, 201.3; HRMS (EI): m/z calcd for C33H55IO4Si, 670.2914; found, 670.2911 (M⁺). Physicochemical properties of 22-epi-63: mp: 44–46 ºC; [a]²⁰D +24.4 (c 0.87 CHCl3);

IR: nmax 1735 (s), 1670 (m), 1458 (w), 1376 (w), 1248 (s), 1032 (m); ¹H NMR (400 MHz): d 0.15 (9H, s), 0.76 (3H, d, J = 6.8 Hz), 0.79 (3H, d, J = 6.8 Hz), 0.82–0.92 (7H, m), 0.97 (3H, s), 1.01–1.85 (19H, m), 1.94–2.07 (6H, m), 2.29 (1H, dt, J = 18.7, 4.1 Hz), 2.51 (1H, ddd, J = 5.2, 10.2, 18.6 Hz), 4.05–4.09 (1H, m), 4.89–4.99 (1H, m), 5.19 (1H, s); ¹³C NMR (100 MHz):

d 0.4 (3C), 15.2, 17.8, 17.9, 18.4, 19.5, 20.2, 21.3, 22.1, 26.2, 27.0, 30.2, 32.38, 32.42, 34.5, 35.0, 35.6, 36.59, 36.62, 37.0, 37.7, 38.5, 41.4, 46.2, 48.5, 70.0, 71.8, 128.7, 161.0, 170.5, 202.6; HRMS (EI): m/z calcd for C33H54SiO4, 670.2914; found, 670.2913 (M⁺).

(3S,4aR,5aS,6R,8R,10bR)-8-((1R,2R,3S)-3-((S)-2,3-dimethylbutyl)-2-methylcyclopentyl)- 8,10b-dimethyl-7-oxo-6-((trimethylsilyl)oxy)-1,3,4,5a,6,7,8,9,10,10b-decahydro-2H-phenanthro[8a,9-b]oxiren-3-yl acetate (22-epi-67)

AcO

O H OTMS H I

22-epi-62

AcO

O H OTMS H I

22-epi-63

In the same manner as described for the preparation of 67, 62 (22.0 mg) gave 22-epi-67 (15.0 mg, 81%). [a]²⁰D –5.1 (c 0.19 CHCl3); IR: nmax 1735 (s), 1704 (m), 1460 (m), 1373 (m), 1246 (s), 1036 (m); ¹H NMR (400 MHz): d 0.13 (9H, s), 0.75 (3H, d, J = 6.4 Hz), 0.78 (3H, d, J = 7.2 Hz), 0.83 (3H, d, J = 6.8 Hz), 0.85 (3H, d, J = 7.2 Hz), 0.96 (3H, s), 0.99–1.37 (7H, m) 1.42–1.82 (11H, m), 1.83–1.90 (1H, m), 1.91–1.99 (1H, m), 2.02–2.12 (4H, m), 2.20 (1H, dt, J = 4.3, 18.7 Hz), 2.30 (1H, t, J = 12.6 Hz), 2.39 (1H, ddd, J = 4.9, 10.1, 18.9 Hz), 3.08 (1H, d, J = 3.2 Hz), 4.90–5.00 (1H, m), 5.06 (1H, d, J = 3.2 Hz); ¹³C NMR (100 MHz): d 0.5 (3C), 15.2, 17.7 (2C), 18.6, 20.3, 21.28, 21.34, 22.3, 26.3, 26.6, 29.3, 29.7, 31.7, 32.3, 34.6, 35.1, 36.5, 36.9, 39.8, 41.4, 45.4, 48.5, 60.4, 60.9, 61.9, 70.7, 128.6, 159.3, 170.2, 201.8; HRMS (EI): m/z calcd for C33H54O5Si, 558.3741; found, 558.3743 (M⁺).

(3S,4aR,5aS,6R,8R,10bR)-8-((1R,2R,3S)-3-((S)-2,3-dimethylbutyl)-2-methylcyclopentyl)-

3,6-dihydroxy-8,10b-dimethyl-1,3,4,6,8,9,10,10b-octahydro-2H-phenanthro[8a,9-b]oxiren-7(5aH)-one (strophasterol B)

In the same manner as described for the preparation of strophasterl A, 22-epi-67 (10.0 mg) gave strophasterol B (6.5 mg, 82%). Mp: 113–115 ºC; [a]²⁰D –16.1 (c 0.20 MeOH); IR: nmax

3446 (br), 1655 (s), 1464 (m), 1377 (m); ¹H NMR (400 MHz): d 0.76 (3H, d, J = 6.8 Hz), 0.79 (3H, d, J = 6.8 Hz), 0.83 (3H, d, J = 7.1 Hz), 0.86 (3H, d, J = 6.8 Hz), 0.96 (3H, s), 1.03–1.40 (9H, m), 1.48–1.84 (9H, m), 1.84–1.90 (1H, m), 1.93–2.06 (3H, m), 2.17–2.30 (2H, m), 2.34–

AcO

O H O OTMS

22-epi-67

HO

O H O OH

strophasterol B

2.45 (1H, m), 2.83 (1H, br s), 3.24 (1H, d, J = 2.7 Hz), 3.96 (1H, tt, J = 5.0, 10.9 Hz), 4.89 (1H, br s); ¹³C NMR (100 MHz): d 15.2, 17.7, 17.8, 18.4, 20.2, 22.2, 22.3, 26.2, 29.2, 30.2, 30.4, 32.0, 32.4, 34.5, 36.7, 36.9, 38.8, 39.6, 41.4, 45.9, 48.6, 59.4, 62.6, 62.9, 68.3, 128.1, 159.4, 205.0; HRMS (EI): m/z calcd for C28H44O4, 444.3240; found, 444.3244 (M⁺).

(2S,4aS,4bS,7R,8aR,10aS)-7-((3R,4R,7R,E)-1-(Ethylthio)-4,7,8-trimethyl-1-oxonon-5-en-3-yl)-4a,7-dimethyl-8-oxotetradecahydrophenanthren-2-yl acetate (71).

To a stirred solution of 35 (0.753 g, 1.54 mmol) in CH2Cl2 (13 mL) were added EtSH (0.342 mL, 4.63 mmol), EDC·HCl (0.443 g, 2.31 mmol), and DMAP (18.8 mg, 0.154 mmol) at room temperature. After 2 h of stirring, the mixture was quenched with satd aq NH4Cl and extracted with CH2Cl2. The extract was washed with brine, dried (MgSO4), and concentrated in vacuo.

The residue was purified by silica gel column chromatography (hexane/EtOAc = 10:1) to give 71 (0.754 g, 92%) as a white amorphous solid. [a]²⁰D –14.3 (c 2.85, CHCl3); IR: nmax 1733 (m), 1699 (m), 1246 (m); ¹H NMR (400 MHz): d 0.81 (3H, d, J = 6.8 Hz), 0.83 (3H, d, J = 6.8 Hz), 0.87 (3H, s), 0.92 (3H, d, J = 6.8 Hz), 0.97 (3H, d, J = 6.4 Hz), 1.09 (3H, s), 1.24 (3H, t, J = 7.4 Hz), 1.00–1.41 (7H, m), 1.42–1.59 (3H, m), 1.60–1.67 (1H, m), 1.69–1.92 (6H, m), 1.92–1.99 (1H, m), 2.02 (3H, s), 2.28 (1H, dq, J = 3.5, 7.2 Hz), 2.40–2.48 (1H, m), 2.48 (1H, dd, J = 5.2, 16.8 Hz), 2.59 (1H, dd, J = 6.0, 16.8 Hz), 2.70 (1H, dt, J = 3.2, 5.6 Hz), 2.87 (2H, q, J = 7.5 Hz), 4.68 (1H, tt, J = 5.4, 11.0 Hz), 5.20 (1H, dd, J = 7.6, 15.2 Hz), 5.30 (1H, dd, J = 8.4, 15.2 Hz); ¹³C NMR (100 MHz): d 12.0, 15.1, 17.9, 20.0, 20.4, 20.6, 21.8, 22.77, 22.81, 23.6, 26.7, 27.7, 27.9, 33.4, 33.6, 34.0, 36.5, 36.8, 38.8, 42.9, 43.5, 43.8, 44.6, 45.6, 52.0, 53.7, 73.6, 133.1, 135.2, 171.0, 200.2, 216.1; HRMS (FAB): m/z calcd for C32H53O4S, 533.3665; found, 533.3659 ([M+H]⁺).

AcO

O OOH H

H 35 H

H

EtSH, EDC DMAP CH₂Cl₂, rt, 92%

AcO

O OSEt H

H 71 H

H

(2S,4aS,7R,10aS)-4a,7-Dimethyl-8-oxo-7-((3R,4R,7R,E)-4,7,8-trimethyl-1-oxonon-5-en-3-yl)-1,2,3,4,4a,5,6,7,8,9,10,10a-dodecahydrophenanthren-2-yl acetate (73).

To a stirred solution of 71 (1.69 g, 3.17 mmol) in THF (40 mL) was added PhNMe3·Br3 (1.31 g, 3.49 mmol) in portions at room temperature. After 1 h of stirring, DBU (0.521 mL, 3.49 mmol) was added. The resulting mixture was stirred at 50 ºC for 12 h, diluted with water, and then extracted with ether. The extract was successively washed with water and brine, dried (MgSO4), and concentrated in vacuo to give 72 as a brown amorphous solid (1.67 g), which was then taken up in acetone (38 mL). To the solution was added 10% Pd/C (0.335 g, 0.315 mmol) in portions at room temperature. Et3SiH (2.50 mL, 15.7 mmol) was then added dropwise over 30 min and the resulting mixture was stirred for 30 min. The mixture was filtered through a pad of Celite, and the filtrate was concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc = 8:1 to 5:1) to give 0.865 g (58% from 71) of 73 as a white solid. Mp 107–108 ºC; [a]²⁰D +74.4 (c 0.77, CHCl3); IR: nmax 1731 (s), 1654 (s), 1246 (s); ¹H NMR (400 MHz): d 0.82 (3H, d, J = 6.8 Hz), 0.84 (3H, d, J = 6.8 Hz), 0.92 (3H, d, J = 6.8 Hz), 0.96 (3H, d, J = 6.8 Hz), 0.97 (3H, s), 1.04 (3H, s), 1.39–1.58 (6H, m), 1.59–

1.74 (3H, m), 1.75–1.82 (1H, m), 1.85–2.00 (4H, m), 2.04 (3H, s), 2.18 (1H, dt, J = 4.1, 13.8 Hz), 2.20–2.31 (1H, m), 2.32–2.48 (2H, m), 2.49–2.57 (3H, m), 4.78 (1H, tt, J = 5.4, 11.0 Hz),

AcO

O OSEt H

H 71 H

H

Me₃NPhBr₃ THF, rt then DBU

50 ºC ^AcO

O OSEt H

H 72

AcO

O H

H 73

H

Pd/C, Et₃SiH, acetone rt, 2 steps 58%

O

5.21–5.30 (2H, m), 9.57–9.59 (1H, m); ¹³C NMR (100 MHz): d 17.6, 17.8, 20.0, 20.1, 20.4, 21.7, 22.2, 22.7, 23.6, 24.7, 27.4, 32.4, 33.4, 33.8, 34.0, 37.5, 38.0, 38.4, 40.0, 41.1, 43.7, 47.1, 73.2, 129.5, 132.2, 135.6, 161.4, 170.9, 202.0, 204.5; HRMS (FAB): m/z calcd for C30H47O4, 471.3474; found, 471.3477 ([M+H]⁺).

(2S,4aS,7R,10aS)-7-((1EZ,3R,4R,5E,7R)-1-(Hydroxyimino)-4,7,8-trimethylnon-5-en-3-yl)-4a,7-dimethyl-8-oxo-1,2,3,4,4a,5,6,7,8,9,10,10a-dodecahydrophenanthren-2-yl acetate (78).

To a stirred solution of 73 (0.401 g, 0.853 mmol) in EtOH (10 mL) were added pyridine (0.687 mL, 8.53 mmol) and NH2OH·HCl (0.118 g, 1.71 mmol) at room temperature. After 30 min of stirring, the mixture was diluted with EtOAc and successively washed with water, satd aq CuSO4, and brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc = 2:1) to give 78 (ca. 1:1 E/Z mixture) as a white amorphous solid (0.415 g, quant). [a]²⁰D +80.0 (c 0.92, CHCl3); IR: nmax 3408 (s), 1733 (s), 1660 (s), 1247 (s); ¹H NMR (400 MHz): d 0.81 (3H, d, J = 6.8 Hz), 0.84 (3H, d, J = 6.8 Hz), 0.92 (3H, d, J = 6.8 Hz), 1.00 (3H, s), 1.03 (3H, s), 1.02–1.07 (3H, m), 1.29–1.53 (5H, m), 1.55–1.71 (2H, m), 1.74–1.80 (1H, m), 1.86–2.08 (6H, m), 2.04 (3H, s), 2.11–2.27 (4H, m), 2.31–2.54 (4H, m), 4.68–4.77 (1H, m), 5.26 (1H, dd, J = 8.0, 15.2 Hz), 5.36 (1H, dd, J = 8.0, 15.2 Hz), 6.54–6.59 (1H ´ 0.5, m, 15-H), 7.24 (1H ´ 0.5, t, J = 6.2 Hz, 15-H); ¹³C NMR (100 MHz): d17.7, 17.84, 17.85, 19.7, 19.9, 20.0, 20.1, 20.4, 21.7, 22.0, 23.2, 23.3, 23.5, 23.6, 24.70, 24.73, 26.3, 27.5, 31.9, 32.2, 33.4, 33.9, 34.01, 34.02, 37.9, 38.0, 38.1, 40.26, 40.29, 43.6, 43.9, 44.1, 47.55, 47.65, 73.2, 129.54, 129.55, 132.3, 132.4, 135.5, 135.6, 153.4, 160.9, 161.0, 170.99, 171.00, 204.6, 204.9; HRMS (FAB): m/z calcd for C30H47NO4, 486.3583; found, 486.3581

AcO

O H

78 H

N OH NH₂OH•HCl

pyridine EtOH, rt quant.

AcO

O OH H

H 73

([M+H]⁺).

(2S,4aS,7R,10aS)-7-((1R,2S,3S)-3-((1S,2R)-1-Hydroxy-2,3-dimethylbutyl)-2-methyl-4-

oxocyclopentyl)-4a,7-dimethyl-8-oxo-1,2,3,4,4a,5,6,7,8,9,10,10a-dodecahydrophenanthren-2-yl acetate (80) and its 22,23-bis-epi isomer (81).

To a stirred solution of 78 (0.100 g, 0.206 mmol) in toluene (5.0 mL) was added NaOCl·5H2O (0.174 g, 0.412 mmol) in portions at 0 ºC. After 10 h of stirring, the mixture was quenched with satd aq Na2S2O3 and extracted with ether. The extract was successively washed with water and brine, dried with (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc = 3:1) to give a ca. 6.4:1 mixture of 79A and 79B as a white amorphous solid (0.090 g, 90%). IR: nmax 1732 (s), 1656 (s), 1245 (m); ¹H NMR (79A, 400 MHz): d 0.86 (3H, d, J = 6.8 Hz), 0.959 (3H, d, J = 6.8 Hz), 0.962 (3H, d, J = 6.8 Hz), 1.01 (3H, s), 1.04 (3H, d, J = 6.8 Hz), 1.05 (3H, s), 1.37 (1H, dt, J = 3.9, 13.3 Hz), 1.42–1.82 (10H, m), 1.88–2.12 (4H, m), 2.04 (3H, s), 2.23–2.34 (1H, m), 2.36 (2H, d, J = 9.2 Hz), 2.39–2.54 (2H, m), 2.65 (1H, q, J = 8.9 Hz), 3.08 (1H, t, J = 10.0 Hz), 4.25 (1H, dd, J = 5.2, 10.4 Hz), 4.73 (1H, tt, J = 5.3, 10.9 Hz); ¹³C NMR (79A, 100 MHz): d 10.7, 18.1, 18.6, 20.1, 20.8, 21.6,

AcO

O H

H 78

N OH

AcO

O H

H 79A N

O

AcO

O H

H 79B N

H H O

+

AcO

O 81 13%

H

AcO H

O 80 81%

H

H

H H

O O

+

HO HO

NaOCl•5H₂O toluene 0 ºC, 90%

H₂, Raney-Ni MeOH/H₂O, rt

21.69, 21.73, 23.7, 24.2 24.7, 27.5, 30.58, 30.63, 34.0, 37.3, 38.1, 40.1, 40.3, 43.2, 45.7, 52.0, 65.3, 73.1, 90.2, 130.0, 161.6, 169.1, 171.0, 203.1; HRMS (FAB): m/z calcd for C30H46NO4, 484.3427; found, 484.3425 ([M+H]⁺). The mixture of 79A and 79B was dissolved in MeOH/H2O (5:1, 3.6 mL). To the solution were added a suspension of Raney Nickel in H2O [“skeletal nickel catalyst slurry in water” (Tokyo Chemical Industry Co., LTD.)] (ca. 0.7 g) and H3BO3 (0.0173 g, 0.279 mmol). The mixture was stirred at room temperature for 8 h under a hydrogen atmosphere. The mixture was filtered through a pad of Celite, and the filtrate was extracted with EtOAc. The extract was successively washed with water and brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc = 3:1–1:1) to give 80 (0.073 g, 81%) as a white amorphous solid and 73 (0.011 g, 13%) as a white amorphous solid. Physical data of 81: [a]²⁰D +46.0 (c 1.32, CHCl3); IR: nmax 3482 (s), 2958 (m), 1732 (m), 1658 (m), 1249 (m); ¹H NMR (600 MHz):

d 0.82 (3H, d, J = 6.6 Hz), 0.89 (3H, d, J = 6.6 Hz), 0.94 (3H, d, J = 6.6 Hz), 1.01 (3H, s), 1.06 (3H, s), 1.11 (3H, d, J = 6.6 Hz), 1.37 (1H, dt, J = 3.6, 13.2 Hz), 1.40–1.55 (4H, m), 1.55–1.81 (5H, m), 1.90–1.99 (2H, m), 2.04 (3H, s), 2.00–2.20 (6H, m), 2.27–2.34 (2H, m), 2.46–2.53 (2H, m), 2.89 (1H, d, J = 5.4 Hz), 3.60–3.64 (1H, m), 4.73 (1H, tt, J = 5.4, 10.7 Hz); ¹³C NMR (150 MHz): d 10.5, 10.9, 18.1, 18.5, 20.5, 21.0, 21.7, 21.8 (2C), 23.7, 24.7, 27.5, 29.7, 31.0, 34.0, 36.0, 38.1, 40.2, 41.6, 42.1, 44.3, 45.1, 59.0, 73.1, 73.5, 130.0, 161.6, 170.9, 203.3, 220.7;

HRMS (FAB): m/z calcd for C30H47O5, 487.3423; found, 487.3424 ([M+H]⁺).

Physical data of 73: [a]²⁰D +96.8 (c 1.60, CHCl3); IR: nmax 3511 (s), 2956 (m), 1732 (m), 1659 (m), 1248 (m); ¹H NMR (600 MHz): d 0.85–0.88 (6H, m), 0.94 (3H, d, J = 6.6 Hz), 1.01 (3H, s), 1.04–1.07 (6H, m), 1.35 (1H, dt, J = 3.6, 13.4 Hz), 1.41–1.54 (4H, m), 1.57–1.65 (2H, m), 1.70–1.81 (2H, m), 1.88–1.98 (3H, m), 2.04 (3H, s), 2.02–2.09 (2H, m), 2.13 (1H, dd, J = 10.2, 19.8 Hz), 2.24–2.40 (4H, m), 2.40–2.49 (2H, m), 2.58 (1H, t, J = 7.2 Hz), 3.23 (1H, d, J = 4.8 Hz), 3.71 (1H, q, J = 5.4 Hz), 4.73 (1H, tt, J = 5.3, 10.8 Hz); ¹³C NMR (150 MHz): d 11.5, 17.2, 17.9, 18.6, 19.8, 21.7, 22.2, 22.9, 23.7, 24.6, 27.2, 27.4, 31.7, 33.9, 34.0, 34.6, 38.0, 38.1, 40.2, 41.6, 42.9, 45.9, 54.9, 73.0, 73.6, 129.7, 161.4, 170.9, 203.4, 221.5; HRMS (FAB): m/z calcd for C30H46O5Na 509.3243; found, 509.3242 ([M+Na]⁺).

To a stirred solution of 78 (1.80 g, 3.71 mmol) in MeOH (50 mL) was added PhI(OAc)2 (1.79 g, 5.56 mmol) in portions at –40 ºC. After 3 h of stirring, the mixture was quenched with satd aq Na2S2O3 and satd aq NaHCO3 and extracted with ether. The extract was successively washed with water and brine, dried with (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc = 3:1) to give a ca. 1.2:1 mixture of 79A and 79B as a white amorphous solid (1.66 g, 92%).

(2S,4aS,7R,10aS)-7-((1R,2S,3R,4R)-4-Hydroxy-3-((1S,2R)-1-hydroxy-2,3-dimethylbutyl)-

2-methylcyclopentyl)-4a,7-dimethyl-8-oxo-1,2,3,4,4a,5,6,7,8,9,10,10a-dodecahydrophenanthren-2-yl acetate (86).

To a stirred solution of 80 (0.342 g, 0.703 mmol) in CH2Cl2 (12 mL) was added NaBH(OAc)3

(1.04 g, 4.92 mmol) at room temperature. After 13 h of stirring, the mixture was quenched with satd aq NaHCO3 and extracted with CH2Cl2. The extract was washed with brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc = 1:1–1:2) to give 86 (0.288 g, 84%) as a white solid. Mp 63–64 ºC; [a]²⁰D

+68.8 (c 2.79, CHCl3); IR: nmax 3447 (s), 2955 (m), 1730 (m), 1653 (m), 1250 (m); ¹H NMR (400 MHz): d 0.90 (6H, d, J = 6.8 Hz), 0.94–0.96 (6H, m), 1.04 (3H, s), 1.11 (3H, d, J = 6.8

AcO

O H

H 78

N OH

AcO

O H

H 79A N

O

AcO

O H

H 79B N

H H O

+

PhI(OAc)₂ TFA MeOH 0 ºC to rt, 92%

(79A/79B = 1.2:1)

AcO

O H

H

H HO

80

O

AcO

O H

H

H

86

OH HO

NaBH(OAc)₃ CH₂Cl₂ rt, 84%

Hz), 1.32–1.85 (14H, m), 1.85–1.99 (3H, m), 2.04 (3H, s), 2.07–2.14 (2H, m), 2.20–2.29 (1H, m), 2.35–2.52 (3H, m), 2.70–2.77 (1H, m), 3.57–3.63 (1H, m), 4.18 (1H, q, J = 6.3 Hz), 4.72 (1H, tt, J = 5.3, 10.7 Hz); ¹³C NMR (100 MHz): d 10.4, 17.7, 19.9, 20.5, 21.6, 21.7, 22.2, 23.1, 23.6, 24.7, 27.4, 30.2, 32.6, 33.7, 34.0, 36.1, 36.6, 38.0, 40.1, 42.2, 45.8, 46.7, 58.3, 73.1, 76.15, 76.18, 129.8 161.4, 170.9, 204.4; HRMS (FAB): m/z calcd for C30H49O5, 489.3580; found, 489.3577 ([M+H]⁺).

(2S,4aS,7R,10aS)-7-((1R,2S,3S,4R)-3-((1S,2R)-1-Hydroxy-2,3-dimethylbutyl)-2-methyl-4-

((phenoxycarbonothioyl)oxy)cyclopentyl)-4a,7-dimethyl-8-oxo-1,2,3,4,4a,5,6,7,8,9,10,10a-

dodecahydrophenanthren-2-yl acetate (86’).

To a stirred solution of 86 (0.918 g, 1.88 mmol) and pyridine (3.03 mL, 37.6 mmol) in CH2Cl2

(17 mL) was added dropwise a solution of PhOC(S)Cl (1.06 mL, 7.90 mmol) in CH2Cl2 (5.0 mL) over 30 min at room temperature. After 30 min of stirring, the mixture was quenched with satd aq NaHCO3 and extracted with CH2Cl2. The extract was successively washed with satd aq CuSO4 and brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc = 10:1) to give 86’ (0.833 g, 71%) as a white amorphous solid. [a]²⁰D +41.2 (c 0.66, CHCl3); IR: nmax 3503 (s), 2958 (s), 1731 (s), 1655 (s);

1H NMR (400 MHz): d 0.85 (3H, d, J = 6.8 Hz), 0.86–0.91 (2H, m), 0.90 (3H, d, J = 6.8 Hz), 0.95 (3H, d, J = 6.8 Hz), 1.03 (3H, s), 1.05 (3H, s), 1.08 (3H, d, J = 6.4 Hz), 1.22–1.86 (11H, m), 1.86–2.15 (6H, m), 2.03 (3H, s), 2.23–2.32 (2H, m), 2.42–2.54 (2H, m), 3.48 (1H, q, J = 6.1 Hz), 4.73 (1H, tt, J = 5.3, 10.8 Hz), 5.66–5.71 (1H, m), 7.07–7.10 (2H, m), 7.27–7.31 (1H, m), 7.39–7.44 (2H, m); ¹³C NMR (100 MHz): d 10.2, 14.4, 17.9, 18.4, 20.6, 21.7, 22.0, 22.1,

AcO

O H

H

H

86

OH HO

AcO

O H

H

H HO

86’

ClC(S)OPh, py.

CH₂Cl₂, rt, 71%

O OPh S

23.0, 23.7, 24.7, 27.4, 29.6, 31.9, 32.2, 33.8, 34.0, 34.2, 36.7, 38.1, 40.2, 41.8, 45.0, 47.7, 56.7, 73.13, 73.15, 87.6, 122.3, 126.8, 129.8, 129.9, 153.5, 161.6, 170.9, 194.7, 203.8; HRMS (FAB):

m/z calcd for C37H52O6SNa, 647.3382; found, 647.3383 ([M+Na]⁺).

(2S,4aS,7R,10aS)-7-((1R,2S,3S)-3-((1S,2R)-1-Hydroxy-2,3-dimethylbutyl)-2-

methylcyclopentyl)-4a,7-dimethyl-8-oxo-1,2,3,4,4a,5,6,7,8,9,10,10a-dodecahydrophenanthren-2-yl acetate (87).

To a stirred solution of 86’ (0.778 g, 1.25 mmol) in benzene (60 mL) were added nBu3SnH (0.654 mL, 2.49 mmol) and AIBN (0.0205 g 0.125 mmol) at 80 ºC. After 1 h of stirring at the same temperature, the mixture was concentrated in vacuo and the residue was purified by column chromatography [SiO2 containing K2CO3 (10 wt. %), hexane/EtOAc = 8:1] to give 87 (0.580 g, 98%) as a white amorphous solid. [a]²⁰D +96.7 (c 1.33, CHCl3); IR: nmax 3525 (s), 2955 (s), 1732 (s), 1656 (s), 1247 (s); ¹H NMR (400 MHz): d 0.79 (3H, d, J = 6.8 Hz), 0.89 (3H, d, J = 6.8 Hz), 0.92 (3H, d, J = 7.2 Hz), 0.98 (3H, s), 1.02 (3H, d, J = 6.4 Hz), 1.04 (3H, s), 1.24–1.41 (5H, m), 1.41–1.55 (7H, m), 1.55–1.84 (6H, m), 1.84–2.06 (4H, m), 2.04 (3H, s), 2.18–2.27 (1H, m), 2.42–2.57 (2H, m), 3.43–3.48 (1H, m), 4.73 (1H, tt, J = 5.4, 10.9 Hz); ¹³C NMR (100 MHz): d 10.3, 17.3, 17.7, 20.1, 20.9, 21.7, 21.9, 22.3, 23.6, 24.4, 24.8, 27.0, 27.5, 29.0, 32.5, 33.8, 34.1, 37.0, 38.0, 40.3, 42.8, 45.9, 48.9, 51.3, 73.2, 73.6, 129.8, 160.9, 171.0, 204.8; HRMS (FAB): m/z calcd for C30H49O4, 473.3631; found, 473.3637 ([M+H]⁺).

(2S,4aS,7R,10aS)-7-((1R,2S,3S)-3-((1S,2R)-2,3-Dimethyl-1-((triethylsilyl)oxy)butyl)-2-

methylcyclopentyl)-4a,7-dimethyl-8-oxo-1,2,3,4,4a,5,6,7,8,9,10,10a-dodecahydrophenanthren-2-yl acetate (88).

AcO

O H

H

H HO

86’

O OPh S

Bu₃SnH, AIBN benzene

80 ºC, 98% AcO

O H

H

H HO

87

To a stirred solution of 87 (0.298 g, 0.631 mmol) in CH2Cl2 (5.0 mL) were added 2,6-lutidine (0.365 mL, 3.15 mmol) and TESOTf (0.170 mL, 0.757 mmol) at room temperature. After 30 min of stirring, the mixture was quenched with satd aq NH4Cl and extracted with CH2Cl2. The extract was washed with brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc = 20:1) to give 88 (0.355 g, 96%) as a white amorphous solid. [a]²⁰D +86.4 (c 1.6, CHCl3); IR: nmax 2954 (s), 1734 (s), 1662 (s), 1244 (s); ¹H NMR (400 MHz): d 057–0.63 (6H, m), 0.75 (3H, d, J = 6.4 Hz), 0.80 (3H, d, J = 6.8 Hz), 0.90 (3H, d, J = 6.4 Hz), 0.94–0.99 (15H, m), 1.04 (3H, s), 1.19–1.71 (14H, m), 1.75–

1.80 (1H, m), 1.84–1.99 (4H, m), 1.99–2.06 (2H, m), 2.04 (3H, s), 2.18–2.26 (1H, m), 2.43–

2.59 (2H, m), 3.58 (1H, dd, J = 2.4, 6.8 Hz), 4.74 (1H, tt, J = 5.3, 10.7 Hz); ¹³C NMR (100 MHz): d 6.1 (3C), 7.5 (3C), 11.4, 17.5, 17.7, 19.8, 19.9, 21.7, 22.2, 22.6, 23.5, 23.6, 24.8, 26.6, 27.5, 28.7, 32.2, 33.8, 34.1, 37.2, 37.9, 40.3, 43.7, 45.5, 48.3, 51.5, 73.2, 74.6, 129.7, 160.6, 170.9, 204.7; HRMS (FAB): m/z calcd for C36H62O4SiNa, 609.4315; found, 609.4319 ([M+Na]⁺).

(2S,4aS,7R,9R,10aR)-9-Bromo-7-((1R,2S,3S)-3-((1S,2R)-2,3-dimethyl-1- ((triethylsilyl)oxy)butyl)-2-methylcyclopentyl)-4a,7-dimethyl-8-oxo-1,2,3,4,4a,5,6,7,8,9,10,10a-dodecahydrophenanthren-2-yl acetate (89).

AcO

O H

H

H HO

87

TESOTf 2,6-lutidine

CH₂Cl₂, rt

96% _AcO

O H

H

H TESO

88

AcO

O H

H

H TESO

88 ^AcO

O H

H

H TESO

89 DDH, V-70

CCl₄, 40 ºC

62% _Br

To a stirred solution of 88 (0.352 g, 0.600 mmol) in CCl4 (30 mL) were successively added DDH (0.094 g, 0.330 mmol) and V-70 (0.019 g, 0.060 mmol) at 40 ºC. After 30 min of stirring at the same temperature, the mixture was concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc = 12:1) to give 89 (0.251 g, 63%) as a white amorphous solid. [a]²⁰D +28.6 (c 0.97, CHCl3); IR: nmax 1735 (s), 1673 (s), 1242 (s); ¹H NMR (400 MHz): d 0.57–0.64 (6H, m), 0.75 (3H, d, J = 6.8 Hz), 0.81 (3H, d, J = 6.8 Hz), 0.89 (3H, d, J = 6.8 Hz), 0.94–0.99 (12H, m), 1.02–1.04 (6H, m), 1.25–1.37 (2H, m), 1.42–1.60 (6H, m), 1.60–1.70 (4H, m), 1.80–1.86 (1H, m), 1.88–2.09 (6H, m), 2.05 (3H, s), 2.20–2.31 (2H, m), 2.51 (1H, ddd, J = 4.9, 10.1, 19.1 Hz), 3.59 (1H, d, J = 4.8 Hz), 4.85 (1H, tt, J = 5.4, 11.0 Hz), 5.46 (1H, brs); ¹³C NMR (100 MHz): d 6.1 (3C), 7.6 (3C), 11.5, 17.7, 18.2, 19.4, 20.3, 21.7, 22.6, 22.7, 24.2, 26.4, 27.4, 28.8, 32.2, 33.1, 33.3, 35.4, 35.7, 37.1, 38.7, 43.7, 46.2, 46.3, 47.3, 51.8, 72.7, 74.6, 131.4, 163.2, 170.8, 202.0; HRMS (FAB): m/z calcd for C36H61O4BrSiNa, 687.3420; found, 687.3417 ([M+Na]⁺).

(2S,4aS,7R,10aR)-7-((1R,2S,3S)-3-((1S,2R)-2,3-Dimethyl-1-((triethylsilyl)oxy)butyl)-2- methylcyclopentyl)-4a,7-dimethyl-8-oxo-1,2,3,4,4a,5,6,7,8,10a-decahydrophenanthren-2-yl acetate (90).

To a stirred solution of PhSeSePh (0.117 g, 0.376 mmol) in EtOH (4.5 mL) was added NaBH4

(0.029 g, 0.753 mmol) at room temperature. After 10 min of stirring, a solution of 89 (0.250 g, 0.376 mmol) in THF (6.0 mL) was added and the stirring was continued for 20 min. To the mixture was then added 30% H2O2 (0.234 mL, 2.07 mmol). The mixture was stirred at room temperature for 1 h, quenched with satd aq Na2S2O3, and extracted with ether. The extract was

PhSeSePh, NaBH₄ EtOH/THF, rt then H₂O₂ aq.

rt, 82%

AcO

O H

H

H TESO

89

Br AcO

O H

H

H TESO

90

successively washed with water and brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc = 10:1) to give 90 (0.180 g, 82%) as a pale yellow amorphous solid. [a]²⁰D +4.7 (c 0.79, CHCl3); IR: nmax 1736 (s), 1667 (s), 1242 (s); ¹H NMR (400 MHz): d 0.60 (6H, dq, J = 1.8, 7.9 Hz), 0.74 (3H, d, J = 6.4 Hz), 0.80 (3H, d, J = 6.8 Hz), 0.89 (3H, d, J = 6.8 Hz), 0.89 (3H, s), 0.94 (3H, d, J = 6.4 Hz), 0.96 (9H, t, J = 8.0 Hz), 0.99 (3H, s), 1.25–1.35 (3H, m), 1.41–1.75 (9H, m), 1.82-1.88 (1H, m), 1.93–2.08 (4H, m), 2.05 (3H, s), 2.29 (1H, dt, J = 19.7, 5.3 Hz), 2.32–2.38 (1H, m), 2.49–2.59 (1H, m), 3.58 (1H, dd, J = 2.0, 6.8 Hz), 4.78 (1H, tt, J = 5.3, 10.8 Hz), 5.50 (1H, dd, J = 2.4, 9.6 Hz), 6.59 (1H, dd, J = 3.2, 9.6 Hz); ¹³C NMR (100 MHz): d 6.1 (3C), 7.6 (3C), 11.4, 12.8, 17.4, 19.6, 20.1, 21.67, 21.71, 22.6, 23.2, 26.5, 27.5, 28.7, 31.0, 32.1, 32.5, 37.3, 38.0, 40.5, 43.8, 45.4, 48.9, 51.3, 73.1, 74.7, 121.3, 128.5, 129.8, 161.6, 170.9, 201.7; HRMS (FAB):

m/z calcd for C36H60O4SiNa, 607.4159; found, 607.4165 ([M+Na]⁺).

(2S,4aS,7R,9R,10R,10aS)-7-((1R,2S,3S)-3-((1S,2R)-2,3-Dimethyl-1-((triethylsilyl)oxy)butyl)-2-

methylcyclopentyl)-4a,7-dimethyl-8-oxo-10-(phenylselanyl)-9-((triethylsilyl)oxy)- 1,2,3,4,4a,5,6,7,8,9,10,10a-dodecahydrophenanthren-2-yl acetate (103).

To a stirred mixture of 90 (0.075 g, 0.129 mmol) and H2O (0.3 mL) in CH2Cl2 (1.5 mL) were added N-(phenylseleno)phthalimide (0.156 g, 0.515 mmol) and TFA (0.015 mL, 0.193 mmol) at room temperature. After 60 h of stirring, the mixture was quenched with satd aq NaHCO3

and extracted with CH2Cl2. The extract was washed with brine, dried (MgSO4), and concentrated in vacuo to give a mixture of 94, 95, 96, and 97 as a white amorphous solid, which was then taken up in pyridine (0.32 mL). To the solution was added TESOTf (0.088 mL, 0.389 mmol) dropwise at –30 ºC. The mixture was stirred for 1 hour, quenched with satd aq NH4Cl, and extracted with CH2Cl2. The extract was successively washed with water and brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc = 20:1) to give 103 (0.063 g, 56% from 90) as a pale yellow amorphous solid. [a]²⁰D +35.4 (c 0.92, CHCl3); IR: nmax 1737 (s), 1667 (s), 1243 (s); ¹H NMR (400 MHz): d 0.54–0.72 (12H, m), 0.76 (3H, d, J = 6.4 Hz), 0.81 (3H, d, J = 6.8 Hz), 0.89 (9H, t, J = 7.8 Hz), 0.88–0.92 (6H, m), 0.95 (3H, s), 0.96 (9H, t, J = 8.0 Hz), 1.23 (3H, s), 1.25–1.35 (6H, m), 1.40–1.71 (10H, m), 1.82 (1H, dt, J = 3.2, 13.2 Hz), 1.86–1.93 (1H, m), 1.99 (1H, dt, J = 3.9, 13.6 Hz), 2.05 (3H, s), 2.20 (1H, dt, J = 4.3, 19.4 Hz), 2.47 (1H, ddd, J = 4.9, 10.3, 19.3 Hz), 2.61–2.67 (1H, m), 3.07 (1H, dd, J = 3.6, 12.0 Hz), 3.56 (1H, dd, J = 2.6, 6.6 Hz), 7.20–

AcO

O H

H

H TESO

90 ^AcO

O H

H

H RO

AcO

O H

H

H RO

+

94: R = TES

95: R = H 96: R = TES 97: R = H

SePh SePh

OH OH

AcO

O H

H

H TESO

OTES SePh

103

TFA CH₂Cl₂, H₂O

rt N O

O SePh

2 steps 56%

TESOTf, rypidine –30 ºC

7.29 (3H, m), 7.52–7.55 (2H, m); ¹³C NMR (100 MHz): d 5.5 (3C), 6.2 (3C), 7.5 (3C), 7.6 (3C), 11.4, 17.1, 17.6, 19.7, 20.0, 21.7, 22.7, 22.8, 23.3, 26.7, 27.4, 28.8, 31.6, 33.3, 34.0, 37.4, 39.5, 43.7, 45.1, 45.8, 48.3, 51.4, 53.9, 70.0, 73.0, 74.7, 128.2, 128.3 (2C), 129.3, 133.3, 136.1 (2C), 165.4, 170.9, 201.9; HRMS (FAB): m/z calcd for C48H80O5Si2SeNa, 895.4607; found, 895.4614 ([M+Na]⁺).

(3S,4aR,5aS,6R,8R,10bR)-8-((1R,2S,3S)-3-((1S,2R)-2,3-Dimethyl-1-((triethylsilyl)oxy)butyl)-2-

methylcyclopentyl)-8,10b-dimethyl-7-oxo-6-((triethylsilyl)oxy)-1,3,4,5a,6,7,8,9,10,10b-decahydro-2H-phenanthro[8a,9-b]oxiren-3-yl acetate (104).

To a stirred solution of 103 (0.103 g, 0.118 mmol) in CH2Cl2 (1.5 mL) were added NaHCO3

(0.099 g, 1.18 mmol) and mCPBA (0.157 g, 0.590 mmol) at 0 ºC. After 1 h of stirring, the mixture was quenched with satd aq Na2S2O3 and extracted with CH2Cl2. The extract was successively washed with satd aq NaHCO3 and brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc = 5:1) to give 104 (0.086 g, quant) as a white amorphous solid. [a]²⁰D +3.9 (c 0.31, CHCl3); IR: nmax

1740 (s), 1664 (s), 1240 (s); ¹H NMR (600 MHz): d 0.57–0.62 (6H, m), 0.63 (6H, q, J = 8.2 Hz), 0.74 (3H, d, J = 6.6 Hz), 0.80 (3H, d, J = 7.2 Hz), 0.89 (3H, d, J = 6.6 Hz), 0.91 (9H, t, J

= 8.1 Hz), 0.96 (9H, t, J = 7.8 Hz), 0.94–0.96 (3H, m), 0.98 (3H, s), 1.24–1.33 (2H, m), 1.37 (3H, s), 1.33–1.50 (3H, m), 1.52–1.70 (5H, m), 1.70–1.76 (1H, m), 1.79 (1H, dt, J = 2.8, 13.4 Hz), 1.85–1.90 (2H, m), 2.01–2.06 (1H, m), 2.04 (3H, s), 2.08–2.12 (1H, m), 2.20 (1H, dt, J = 4.7, 19.0 Hz), 2.30 (1H, t, J = 12.3 Hz), 2.43 (1H, ddd, J = 4.8, 9.9, 18.9 Hz), 3.11 (1H, d, J =

AcO

O H

H TESO

O OTES 104 AcO

O H

H

H TESO

OTES SePh

mCPBA NaHCO₃ CH₂Cl₂ 0 ºC, quant.

103

3.0 Hz), 3.46 (1H, dd, J = 2.1, 6.9 Hz), 4.96 (1H, tt, J = 5.4, 11.0 Hz), 5.08 (1H, d, J = 3.0 Hz);

13C NMR (150 MHz): d 5.2 (3C), 6.1 (3C), 7.2 (3C), 7.6 (3C), 11.4, 17.5, 19.7, 19.9, 21.6, 21.7, 22.56, 22.63, 23.4, 26.5, 27.0, 28.7, 29.8, 31.6, 35.4, 37.2, 40.2, 43.7, 45.1, 47.7, 51.4, 60.9, 61.1, 62.3, 71.1, 74.6, 129.0, 159.8, 170.6, 202.3; HRMS (FAB): m/z calcd for C42H74O6Si2Na, 753.4922; found, 753.4922 ([M+Na]⁺).

(3S,4aR,5aS,6R,8R,10bR)-3,6-Dihydroxy-8-((1R,2S,3S)-3-((1S,2R)-1-hydroxy-2,3- dimethylbutyl)-2-methylcyclopentyl)-8,10b-dimethyl-1,3,4,6,8,9,10,10b-octahydro-2H-phenanthro[8a,9-b]oxiren-7(5aH)-one (strophasterol F).

To a stirred solution of 104 (9.1 mg, 0.013 mmol) in MeOH (0.3 mL) was added TsOH (azeotropically dried with toluene, 6.4 mg, 0.037 mmol) at room temperature. After 30 min of stirring, a solution of KOH (1.4 mg, 0.249 mmol) in MeOH (0.3 mL) was added, and the stirring was continued for 1 h. The mixture was diluted with water and extracted with EtOAc. The extract was washed with brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc = 1:10) to give strophasterol F (4.9 mg, 85%) as a white amorphous solid. [a]²⁰D –3.9 (c 0.50, EtOH); IR: nmax 3446 (s), 1652 (s), 1466 (s); ¹H NMR (400 MHz): d 0.78 (3H, d, J = 6.8 Hz), 0.89 (3H, d, J = 6.8 Hz), 0.91 (3H, d, J = 6.8 Hz), 0.99 (3H, d, J = 6.4 Hz), 0.99 (3H, s), 1.33 (3H, s), 1.31–1.78 (14H, m), 1.86–1.91 (1H, m), 1.94 (1H, q, J = 8.1 Hz), 2.00–2.10 (2H, m), 2.19–2.29 (2H, m), 2.37–2.46 (1H, m), 2.85 (1H, d, J = 3.6 Hz), 3.24 (1H, d, J = 2.8 Hz), 3.42–3.48 (1H, m), 3.92–4.01 (1H, m), 4.87–4.90 (1H, m); ¹³C NMR (150 MHz): d 10.0, 16.8, 19.4, 20.3, 21.6, 22.0, 22.4, 23.9, 26.4, 28.6, 29.3, 30.3, 31.6, 36.6, 38.7, 39.6, 42.5, 45.6, 48.0, 50.8, 59.4, 62.6, 62.8, 68.2, 73.2,

AcO

O H

H TESO

O OTES 104

HO

O H

H HO

O OH

strophasterol F TsOH

MeOH, rt then KOH, rt

85%

128.2, 159.8, 205.4; HRMS (FAB): m/z calcd for C28H45O5, 461.3267; found, 461.3270 ([M+H]⁺).

(3S,4aR,5aS,6R,8R,10bR)-8-((1R,2S,3S)-3-((1S,2R)-1-Hydroxy-2,3-dimethylbutyl)-2- methylcyclopentyl)-8,10b-dimethyl-7-oxo-6-((triethylsilyl)oxy)-1,3,4,5a,6,7,8,9,10,10b-decahydro-2H-phenanthro[8a,9-b]oxiren-3-yl acetate (104’).

To a stirred solution of 104 (18.1 mg, 0.246 mmol) in CH2Cl2/EtOH (1:1, 0.4 mL) was added TsOH (azeotropically dried with toluene, 8.5 mg, 0.049 mmol) at –30 ºC. After 5 h of stirring at the same temperature, the mixture was quenched with satd aq NaHCO3 and extracted with CH2Cl2. The extract was washed with brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc = 5:1 to 2:1) to give 104’ (10.2 mg, 67%) as a white amorphous solid. [a]²⁰D –1.3 (c 0.73, CHCl3); IR: nmax 3525 (s), 1738 (s), 1661 (s), 1241(s); ¹H NMR (400 MHz): d 0.63 (6H, q, J = 7.7 Hz), 0.78 (3H, d, J

= 6.8 Hz), 0.89 (3H, d, J = 6.8 Hz), 0.91 (3H, d, J = 6.8 Hz), 0.91 (9H, t, J = 7.8 Hz), 0.98–1.01 (6H, m), 1.25–1.80 (13H, m), 1.37 (3H, s), 1.82–1.89 (2H, m), 1.99–2.12 (2H, m), 2.04 (3H, s), 2.20 (1H, dt, J = 4.6, 19.2 Hz), 2.30 (1H, dd, J = 12.0, 12.8 Hz), 2.41 (1H, ddd, J = 4.9, 10.1, 19.1 Hz), 3.11 (1H, d, J = 3.2 Hz), 3.43–3.47 (1H, m), 4.96 (1H, tt, J = 5.3, 10.9 Hz), 5.10 (1H, d, J = 3.2 Hz); ¹³C NMR (100 MHz): d 5.2 (3C), 7.2 (3C), 10.3, 17.2, 20.1, 20.8, 21.6, 21.9, 22.6, 23.0, 24.5, 26.8, 26.9, 29.0, 29.8, 32.0, 35.4, 36.9, 40.2, 42.9, 45.6, 48.2, 51.3, 60.9, 61.2, 62.2, 71.0, 73.6, 129.2, 160.0, 170.6, 202.4; HRMS (FAB): m/z calcd for C36H61O6Si, 617.4237;

found, 617.4237 ([M+H]⁺).

TsOH•H₂O CH₂Cl₂, EtOH

–30 ºC, 67% ^AcO

O H

H

O OTES HO

104’

AcO

O H

H TESO

O OTES 104

(3S,4aR,5aS,6R,8R,10bR)-8-((1R,2S,3S)-3-((R)-2,3-Dimethylbutanoyl)-2- methylcyclopentyl)-3,6-dihydroxy-8,10b-dimethyl-1,3,4,6,8,9,10,10b-octahydro-2H-phenanthro[8a,9-b]oxiren-7(5aH)-one (strophasterol C).

To a stirred mixture of 104’ (13.2 mg, 21.4 µmol) and satd aq NaHCO3 (0.15 mL) in CH2Cl2

(0.6 mL) were successively added AZADOL (0.3 mg, 2.1 µmol), KBr (2.6 mg, 21.4 µmol), and 8% NaOCl aq (0.123 mL, 85.7 µmol) at room temperature. After 3 h of stirring, the mixture was quenched with satd aq Na2S2O3 and extracted with CH2Cl2. The extract was washed with brine, dried (MgSO4), and concentrated in vacuo to give 105 as a white amorphous solid, which was then taken up in MeOH (0.4 mL). To the solution was added Mg (1.0 mg, 41.1 µmol) at 50 ºC while stirring. After 1 h, TsOH (azeotropically dried with toluene, 4.9 mg, 28.5 µmol) was added at room temperature and the stirring was continued for 20 min. The mixture was quenched with satd aq NaHCO3 and extracted with EtOAc. The extract was successively washed with water and brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc = 1:10) to give strophasterol C (6.3 mg, 67% form 104’) as a white amorphous solid. [a]²⁰D –19.0 (c 0.21, MeOH); IR: nmax

3445 (s), 1702 (s), 1655 (s), 1458 (s); ¹H NMR (400 MHz): d 0.81 (3H, d, J = 6.8 Hz), 0.88

AZADOL, NaOCl KBr, NaHCO₃ CH₂Cl₂, H₂O, rt

AcO

O H

H

O OTES O

Mg, MeOH, 50 ºC

then TsOH, rt, 2 steps 67%

HO

O H

H

O OH

O 105

strophasterol C AcO

O H

H

O OTES HO

104’

(3H, d, J = 6.8 Hz), 0.93 (3H, d, J = 6.4 Hz), 0.96 (3H, d, J = 6.8 Hz), 0.99 (3H, s), 1.31 (3H, s), 1.40–1.75 (8H, m), 1.80–2.09 (6H, m), 2.15–2.26 (3H, m), 2.32–2.42 (2H, m), 2.58 (1H, q, J = 8.3 Hz), 2.80 (1H, d, J = 2.8 Hz), 3.21 (1H, d, J = 2.8 Hz), 3.89–3.98 (1H, m), 4.85 (1H, brs); ¹³C NMR (100 MHz): d 12.6, 18.6, 19.2, 20.5, 21.4, 21.9, 22.3, 27.1, 29.2, 29.5, 30.0, 30.3, 31.2, 36.9, 38.7, 39.5, 45.3, 47.2, 52.1, 59.2, 60.4, 62.5, 62.9, 68.2, 128.0, 159.8, 205.0, 216.5; HRMS (FAB): m/z calcd for C28H43O5, 459.3110; found, 459.3110 ([M+H]⁺).

(3S,4aR,5aS,6R,8R,10bR)-3,6-Dihydroxy-8-((1R,2S,3S)-3-((1R,2R)-1-Hydroxy-2,3- dimethylbutyl)-2-methylcyclopentyl)-8,10b-dimethyl-1,3,4,6,8,9,10,10b-octahydro-2H-phenanthro[8a,9-b]oxiren-7(5aH)-one (strophasterol E).

To a stirred solution of strophasterol C (7.80 mg, 17.0 µmol) in MeOH (0.3 mL) was added BH3·NH3 (5.20 mg, 170 µmol) at room temperature. After 5 h of stirring, additional BH3·NH3

(2.60 mg, 85.1 µmol) was added, and the stirring was continued for 3 h. The mixture was quenched with satd aq NaHCO3 and extracted with EtOAc. The extract was washed with brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (CH2Cl2/MeOH = 30:1) to give strophasterol E (3.2 mg, 41%) as a white amorphous solid. [a]²⁰D –5.0 (c 0.20, EtOH); IR: nmax 3421 (s), 1653 (s), 1457 (s), 1377(s); ¹H NMR (400 MHz): d 0.79 (3H, d, J = 7.2 Hz), 0.81 (3H, d, J = 7.2 Hz), 0.92 (3H, d, J = 6.8 Hz), 1.03 (3H, s), 1.11 (3H, d, J = 6.8 Hz), 1.33 (3H, s), 1.37–1.46 (2H, m), 1.48–1.76 (9H, m), 1.76–1.90 (3H, m), 1.96–2.14 (4H, m), 2.22 (1H, dd, J = 11.4, 13.0 Hz), 2.21–2.30 (1H, m), 2.37–2.46 (1H, m), 2.82 (1H, d, J = 3.6 Hz), 3.24 (1H, d, J = 2.4 Hz), 3.33–3.36 (1H, m), 3.92–

4.01 (1H, m), 4.91 (1H, brs); ¹³C NMR (100 MHz): d 10.5, 16.2, 19.9, 22.1, 22.2, 22.5, 24.0,

HO

O H

H

O OH

O

strophasterol C

HO

O H

H

O OH

HO

strophasterol E BH₃•NH₃

MeOH, rt 41%

26.3, 27.7, 29.3, 30.4, 30.5, 32.3, 35.9, 38.7, 39.6, 41.5, 45.8, 50.3, 50.8, 59.3, 62.6, 62.8, 68.2, 78.9, 128.3, 160.0, 205.7; HRMS (FAB): m/z calcd for C28H44O5Na, 483.3086; found, 482.3088 ([M+Na]⁺).

(2S,4aS,7R,10aS)-7-((1R,2S,3R,4R)-4-hydroxy-3-((1S,2R)-1-hydroxy-2,3-dimethylbutyl)-

2-methylcyclopentyl)-4a,7-dimethyl-8-oxo-1,2,3,4,4a,5,6,7,8,9,10,10a-dodecahydrophenanthren-2-yl acetate (136)

In the same manner as described for the preparation of 86, 81 (0.212 g) gave 136 (0.196 g, 92%). [a]²⁰D +87.1 (c 1.64, CHCl3); IR: nmax 3447 (s), 1732 (s), 1658 (s), 1375 (w), 1247 (s);

1H NMR (400 MHz): d 0.88–0.95 (12H, m), 1.00 (3H, s), 1.05 (3H, s), 1.31–1.66 (8H, m), 1.75–2.10 (11H, m), 2.04 (3H, s), 2.22–2.31 (1H, m), 2.37–2.50 (2H, m), 2.84 (1H, d, J = 2.8 Hz), 3.61 (1H, brs), 3.76–3.81 (1H, m), 4.20 (1H, q, J = 8.3 Hz), 4.73 (1H, tt, J = 5.1, 10.1 Hz);

13C NMR (100 MHz): d 11.2, 17.6, 17.8, 19.0, 19.2, 21.4, 21.8, 23.1, 23.4, 24.4, 26.6, 27.2, 30.9, 33.6, 33.7, 34.1, 34.6, 37.7, 39.9, 41.5, 45.7, 45.8, 50.8, 72.8, 75.3, 78.0, 129.6, 160.6, 170.6, 203.6; HRMS (FAB): m/z calcd for C30H49O5, 489.3580; found, 489.3580 ([M+H]⁺).

(2S,4aS,7R,10aS)-7-((1R,2S,3S,4R)-3-((1S,2R)-1-hydroxy-2,3-dimethylbutyl)-2-methyl-4-

((phenoxycarbonothioyl)oxy)cyclopentyl)-4a,7-dimethyl-8-oxo-1,2,3,4,4a,5,6,7,8,9,10,10a-dodecahydrophenanthren-2-yl acetate (136’)

AcO

O H

H

H

136

OH HO

In the same manner as described for the preparation of 86’, 136 (0.117 g) gave 136’ (0.112 g, 75%). [a]²⁰D +60.5 (c 0.815, CHCl3); IR: nmax 3524 (s), 1731 (s), 1654 (m), 1373 (w), 1247 (s);

1H NMR (400 MHz): d 0.77 (3H, d, J = 6.8 Hz), 0.81 (3H, d, J = 6.8 Hz), 0.88 (2H, t, J = 6.8 Hz), 0.95 (3H, d, J = 6.8 Hz), 1.02 (3H, s), 1.04 (3H, s), 1.07 (3H, d, J = 7.2 Hz), 1.24–1.81 (9H, m), 1.86–2.18 (7H, m), 2.04 (3H, s), 2.21–2.30 (2H, m), 2.32–2.38 (1H, m), 2.41–2.54 (2H, m), 3.57–3.62 (1H, m), 4.74 (1H, tt, J = 5.3, 10.8 Hz), 5.74 (1H, q, J = 7.1 Hz), 7.06–7.10 (2H, m), 7.26–7.31 (1H, m), 7.38–7.44 (2H, m); ¹³C NMR (100 MHz): d 10.5, 14.1, 15.6, 17.5, 17.6, 19.1, 21.4, 21.8, 22.0, 22.7, 23.3, 24.4, 26.5, 27.1, 31.6, 32.7, 33.5, 33.7, 35.8, 37.7, 39.9, 42.1, 45.0, 45.1, 49.3, 72.77, 72.82, 85.6, 122.0, 126.5, 129.48, 129.50, 153.3, 160.9, 170.6, 194.4, 203.5; HRMS (FAB): m/z calcd for C37H52O6Na, 647.3382; found, 647.3383 ([M+Na]⁺).

(2S,4aS,7R,10aS)-7-((1R,2S,3S)-3-((1S,2R)-1-hydroxy-2,3-dimethylbutyl)-2-

methylcyclopentyl)-4a,7-dimethyl-8-oxo-1,2,3,4,4a,5,6,7,8,9,10,10a-dodecahydrophenanthren-2-yl acetate (137)

In the same manner as described for the preparation of 87, 136’ (0.0275 g) gave 137 (0.0208 g, quant.). [a]²⁰D +90.0 (c 0.900, CHCl3); IR: nmax 3527 (s), 1732 (s), 1659 (m), 1375 (w), 1247 (s); ¹H NMR (400 MHz): d 0.81 (3H, d, J = 6.8 Hz), 0.84 (3H, d, J = 6.8 Hz), 0.92 (3H, d, J = 6.8 Hz), 0.95 (3H, s), 0.97 (3H, d, J = 6.8 Hz), 1.04 (3H, s), 1.22 (1H, brs), 1.30–1.40 (3H, m), 1.40–2.06 (18H, m), 2.04 (3H, s), 2.19–2.28 (1H, m), 2.40–2.55 (2H, m), 3.49–3.54 (1H, m),

AcO

O H

H

H HO

136’

O OPh S

AcO

O H

H

H HO

137

4.73 (1H, tt, J = 5.2, 10.6 Hz); ¹³C NMR (100 MHz): d 11.1, 17.0, 17.4, 18.0, 18.7, 21.4, 22.1, 22.5, 23.3, 24.4, 25.3, 26.2, 26.7, 27.1, 32.3, 33.5, 33.7, 36.4, 37.6, 40.0, 42.3, 45.6, 46.1, 48.5, 72.9, 75.2, 129.4, 160.4, 170.6, 204.1; HRMS (EI): m/z calcd for C30H48O4, 472.3553; found, 472.3550 (M⁺).

(2S,4aS,7R,10aS)-7-((1R,2S,3R)-3-((1R,2R)-2,3-dimethyl-1-((triethylsilyl)oxy)butyl)-2-

methylcyclopentyl)-4a,7-dimethyl-8-oxo-1,2,3,4,4a,5,6,7,8,9,10,10a-dodecahydrophenanthren-2-yl acetate (138)

In the same manner as described for the preparation of 88, 137 (0.120 g) gave 138 (0.144 g, 97%). [a]²⁰D +65.1 (c 1.18, CHCl3); IR: nmax 1735 (s), 1662 (m), 1375 (w), 1245 (s); ¹H NMR (400 MHz): d 0.60 (6H, q, J = 7.9 Hz), 0.85–0.89 (9H, m), 0.91 (3H, d, J = 6.8 Hz), 0.93 (3H, s), 0.95 (9H, t, J = 8.0 Hz), 1.04 (3H, s), 1.25–1.66 (10H, m), 1.67–2.07 (11H, m), 2.04 (3H, s), 2.18–2.21 (1H, m), 2.37–2.54 (2H, m), 3.68 (1H, dd, J = 2.4, 8.0 Hz), 4.73 (1H, tt, J = 5.2, 10.7 Hz); ¹³C NMR (100 MHz): d 5.6 (3C), 7.2 (3C), 12.8, 17.4, 18.0, 18.7, 19.4, 21.4, 22.1, 23.1, 23.3, 24.5, 25.7, 27.1, 27.8, 28.3, 32.3, 33.5, 33.7, 35.8, 37.7, 40.0, 43.1, 45.9, 47.1, 49.1, 72.9, 76.8, 129.4, 160.2, 170.6, 204.0; HRMS (FAB): m/z calcd for C36H62O4SiNa, 609.4315; found, 609.4312 ([M+Na]⁺).

(2S,4aS,7R,9R,10aR)-9-bromo-7-((1R,2S,3R)-3-((1R,2R)-2,3-dimethyl-1- ((triethylsilyl)oxy)butyl)-2-methylcyclopentyl)-4a,7-dimethyl-8-oxo-1,2,3,4,4a,5,6,7,8,9,10,10a-dodecahydrophenanthren-2-yl acetate (139)

AcO

O H

H

H TESO

138

In the same manner as described for the preparation of 89, 138 (0.132 g) gave 139 (0.0792 g, 53%). [a]²⁰D +30.2 (c 1.03, CHCl3); IR: nmax 1736 (s), 1673 (m), 1375 (w), 1242 (s); ¹H NMR (400 MHz): d 0.60 (6H, q, J = 8.0 Hz), 0.85–0.90 (9H, m), 0.91 (3H, d, J = 6.8 Hz), 0.95 (3H, s), 0.95 (9H, t, J = 8.0 Hz), 1.03 (3H, s), 1.18–1.30 (1H, m), 1.35–1.98 (16H, m), 1.98–2.06 (2H, m), 2.05 (3H, s), 2.18–2.31 (2H, m), 2.43 (1H, ddd, J = 5.3, 10.1, 18.7 Hz), 3.66 (1H, dd, J = 2.2, 8.2 Hz), 4.84 (1H, tt, J = 5.5, 11.0 Hz), 5.43 (1H, brs); ¹³C NMR (100 MHz): d 5.6 (3C), 7.2 (3C), 12.8, 17.7, 18.1, 18.3, 19.3, 21.4, 22.4, 23.2, 25.5, 27.0, 27.7, 28.4, 32.6, 32.7, 32.9, 35.0, 35.4, 35.7, 38.3, 42.9, 45.7, 46.4, 47.3, 48.5, 72.3, 77.1, 131.4, 162.9, 170.5, 201.2;

HRMS (FAB): m/z calcd for C36H61O4BrSiNa, 687.3420; found, 687.3422 ([M+Na]⁺).

(2S,4aS,7R,10aR)-7-((1R,2S,3R)-3-((1R,2R)-2,3-dimethyl-1-((triethylsilyl)oxy)butyl)-2- methylcyclopentyl)-4a,7-dimethyl-8-oxo-1,2,3,4,4a,5,6,7,8,10a-decahydrophenanthren-2-yl acetate (140)

In the same manner as described for the preparation of 90, 139 (0.0710 g) gave 140 (0.0488 g, 78%). [a]²⁰D –3.0 (c 0.57, CHCl3); IR: nmax 1735 (s), 1667 (m), 1362 (w), 1241 (s); ¹H NMR (400 MHz): d 0.60 (6H, q, J = 7.9 Hz), 0.85–0.92 (15H, m), 0.95 (3H, s), 0.95 (9H, t, J = 8.0), 1.20–1.31 (1H, m), 1.35–2.02 (15H, m), 2.02–2.11 (1H, m), 2.05 (3H, s), 2.21–2.36 (2H, m), 2.50 (1H, dt, J = 6.6, 19.9 Hz), 3.68 (1H, dd, J = 2.6, 8.2 Hz), 4.77 (1H, tt, J = 5.4, 10.9 Hz), 5.50 (1H, dd, J = 2.0, 9.6 Hz), 6.56 (1H, dd, J = 3.2, 9.6 Hz); ¹³C NMR (100 MHz): d 5.6 (3C),

AcO

O H

H

H TESO

139 Br

AcO

O H

H

H TESO

140

7.2 (3C), 12.5, 12.8, 18.0, 19.0, 19.4, 21.4, 21.5, 23.1, 25.5, 27.2, 27.8, 28.2, 30.9, 31.7, 32.1, 36.2, 37.7, 40.2, 43.1, 46.1, 47.1, 49.9, 72.7, 76.9, 121.0, 128.1, 129.5, 161.2, 170.6, 201.3;

HRMS (FAB): m/z calcd for C36H60O4SiNa, 607.4159; found, 607.4165 ([M+Na]⁺).

(2S,4aS,7R,9R,10R,10aS)-7-((1R,2S,3R)-3-((1R,2R)-2,3-dimethyl-1- ((triethylsilyl)oxy)butyl)-2-methylcyclopentyl)-4a,7-dimethyl-8-oxo-10-(phenylselanyl)-9-((triethylsilyl)oxy)-1,2,3,4,4a,5,6,7,8,9,10,10a-dodecahydrophenanthren-2-yl acetate (141)

In the same manner as described for the preparation of 103, 140 (0.0582 g) gave 141 (0.0458 g, 52%). [a]²⁰D +11.7 (c 0.57, CHCl3); IR: nmax 1735 (s), 1668 (m), 1242 (s); ¹H NMR (400 MHz): d 0.54–0.75 (12H, m), 0.82 (3H, d, J = 6.8 Hz), 0.86–0.91 (18H, m), 0.93 (3H, s), 0.97 (9H, t, J = 8.0), 1.18–1.42 (7H, m), 1.22 (3H, s), 1.50–1.77 (7H, m), 1.77–1.92 (3H, m), 2.04 (3H, s), 2.17–2.26 (1H, m), 2.36–2.46 (1H, m), 2.58–2.64 (1H, m), 3.08 (1H, dd, J = 3.8, 11.8 Hz), 3.68 (1H, dd, J = 2.4, 8.0 Hz), 4.54–4.63 (1H, m), 5.20 (1H, d, J = 3.6 Hz), 7.21–7.28 (3H, m), 7.52–7.55 (2H, m); ¹³C NMR (100 MHz): d 5.1 (3C), 5.6 (3C), 7.1 (3C), 7.2 (3C), 12.8, 16.9, 18.1, 18.9, 19.5, 21.4, 22.4, 23.1, 25.9, 27.0, 27.9, 28.2, 31.7, 33.0, 33.6, 35.7, 39.1, 43.3, 45.4, 45.5, 46.9, 49.6, 53.6, 69.6, 72.6, 76.7, 127.8, 128.2, 129.0 (2C), 133.0, 135.5 (2C), 164.4, 170.6, 201.1; HRMS (FAB): m/z calcd for C48H80O5Si2SeNa, 895.4607; found, 895.4600 ([M+Na]⁺).

(3S,4aR,5aS,6R,8R,10bR)-8-((1R,2S,3R)-3-((1R,2R)-2,3-dimethyl-1-

((triethylsilyl)oxy)butyl)-2-methylcyclopentyl)-8,10b-dimethyl-7-oxo-6-((triethylsilyl)oxy)-1,3,4,5a,6,7,8,9,10,10b-decahydro-2H-phenanthro[8a,9-b]oxiren-3-yl acetate (142)

AcO

O H

H

H TESO

OTES SePh

141

In the same manner as described for the preparation of 104, 141 (0.0267 g) gave 142 (0.0206 g, 92%). [a]²⁰D –6.6 (c 0.65, CHCl3); IR: nmax 1741 (s), 1668 (m), 1241 (s); ¹H NMR (400 MHz): d 0.56–0.66 (12H, m), 0.84–0.98 (33H, m), 1.25–1.43 (4H, m), 1.36 (3H, s), 1.54 (1H, ddd, J = 2.0, 4.9, 13.0 Hz), 1.64–1.95 (10H, m), 2.03 (3H, s), 2.06–2.12 (1H, m), 2.21 (1H, dt, J = 19.2, 4.7 Hz), 2.30 (1H, dd, J = 12.2, 13.0 Hz), 2.31–2.41 (1H, m), 3.10 (1H, d, J = 3.2 Hz), 3.67 (1H, dd, J = 2.4, 8.0 Hz), 4.95 (1H, tt, J = 5.3, 11.0 Hz), 5.11 (1H, d, J = 3.2 Hz); ¹³C NMR (100 MHz): d 4.9 (3C), 5.6 (3C), 6.9 (3C), 7.2 (3C), 12.8, 18.1, 18.9, 19.4, 21.3, 21.4, 22.3, 23.1, 25.8, 26.6, 27.9, 28.3, 29.4, 31.6, 35.1, 35.8, 39.8, 43.2, 45.5, 47.0, 49.1, 60.5, 60.9, 61.8, 70.7, 76.9, 128.8, 159.0, 170.2, 201.5; HRMS (FAB): m/z calcd for C42H74O6Si2Na, 753.4922;

found, 753.4919 ([M+Na]⁺).

(3S,4aR,5aS,6R,8R,10bR)-3,6-dihydroxy-8-((1R,2S,3R)-3-((1R,2R)-1-hydroxy-2,3- dimethylbutyl)-2-methylcyclopentyl)-8,10b-dimethyl-1,3,4,6,8,9,10,10b-octahydro-2H-phenanthro[8a,9-b]oxiren-7(5aH)-one (glaucoposterol (proposed)) (11)

In the same manner as described for the preparation of strophasterol F, 142 (8.1 mg) gave 11 (5.2 mg, quant.). [a]²⁰D –13.3 (c 0.31, CHCl3); IR: nmax 3458 (vs), 1741 (s), 1658 (m), 1379 (m); ¹H NMR (400 MHz): d 0.80 (3H, d, J = 7.2 Hz), 0.84 (3H, d, J = 6.8 Hz), 0.93 (3H, d, J =

AcO

O H

H TESO

O OTES 142

HO

O H

H HO

O OH

graucoposterol A (11) (proposed)

7.2 Hz), 0.95 (3H, d, J = 6.8 Hz), 0.97 (3H, s), 1.11–1.32 (3H, m), 1.33 (3H, s), 1.36–1.79 (8H, m), 1.79–1.93 (3H, m), 1.95–2.08 (4H, m), 2.22 (1H, dd, J = 11.4, 13.0 Hz), 2.22–2.30 (1H, m), 2.36–2.45 (1H, m), 2.82 (1H, d, J = 3.2 Hz), 3.24 (1H, d, J = 2.8 Hz), 3.51 (1H, t, J = 5.8 Hz), 3.92–4.01 (1H, m), 4.89 (1H, brs); ¹³C NMR (100 MHz): d 11.0, 16.9, 18.0, 18.5, 22.2, 22.4, 22.5, 25.2, 26.1, 26.7, 29.3, 30.3, 31.7, 36.5, 38.7, 39.6, 42.3, 45.6, 46.0, 48.2, 59.3, 62.6, 62.9, 68.2, 75.0, 128.1, 159.6, 204.9; HRMS (FAB): m/z calcd for C28H44O5Na, 483.3086; found, 483.3080 ([M+Na]⁺).

(3S,4aR,5aS,6R,8R,10bR)-8-((1R,2S,3R)-3-((1R,2R)-1-hydroxy-2,3-dimethylbutyl)-2- methylcyclopentyl)-8,10b-dimethyl-7-oxo-6-((triethylsilyl)oxy)-1,3,4,5a,6,7,8,9,10,10b-decahydro-2H-phenanthro[8a,9-b]oxiren-3-yl acetate (142’)

In the same manner as described for the preparation of 104’, 142 (11.9 mg) gave 142’ (7.0 mg, 70%). [a]²⁰D –9.6 (c 0.35, CHCl3); IR: nmax 3565 (s), 1739 (s), 1663 (m), 1377 (m), 1240 (s);

1H NMR (600 MHz): d 0.62 (6H, q, J = 7.8 Hz), 0.81 (3H, d, J = 7.2 Hz), 0.84 (3H, d, J = 7.2 Hz), 0.90–0.96 (6H,m), 0.91 (9H, t, J = 7.8 Hz), 0.96 (3H, s), 1.09–1.18 (1H, m), 1.27–1.48 (4H, m), 1.37 (3H, s), .1.54 (1H, ddd, J = 1.8, 4.8, 13.2 Hz), 1.65–1.79 (4H, m), 1.81–1.98 (5H, m), 1.99–2.05 (1H, m), 2.04 (3H, s), 2.07–2.11 (1H, m), 2.21 (1H, dt, J = 18.8, 4.7 Hz), 2.30 (1H, t, J = 12.6 Hz), 2.39 (1H, ddd, J = 4.8, 9.6, 19.2 Hz), 3.10 (1H, d, J = 3.0 Hz), 3.50 (1H, t, J = 5.7 Hz), 4.95 (1H, tt, J = 5.4, 11.0 Hz), 5.10 (1H, d, J = 3.6 Hz); ¹³C NMR (150 MHz): d 4.9 (3C), 6.9 (3C), 11.1, 17.0, 18.1, 18.8, 21.3, 21.4, 22.3, 22.6, 25.5, 26.2, 26.6, 26.7, 29.4, 31.6, 35.1, 36.3, 39.8, 42.3, 45.3, 46.2, 48.5, 60.5, 60.9, 61.8, 70.7, 75.3, 128.8, 159.3, 170.2, 201.5;

HRMS (FAB): m/z calcd for C36H60O6SiNa, 639.4057; found, 439.4061 ([M+Na]⁺).

AcO

O H

H HO

O OTES 142’

(3S,4aR,5aS,6R,8R,10bR)-8-((1R,2S,3R)-3-((R)-2,3-dimethylbutanoyl)-2- methylcyclopentyl)-3,6-dihydroxy-8,10b-dimethyl-1,3,4,6,8,9,10,10b-octahydro-2H-phenanthro[8a,9-b]oxiren-7(5aH)-one (strophasterol D (putative)) (8)

In the same manner as described for the preparation of strophasterol C, 142’ (11.5 mg) gave 8 (4.7 mg, 55% from 142’). [a]²⁰D –49.7 (c 0.21, CHCl3); IR: nmax 3446 (s), 1700 (s), 1654 (m);

1H NMR (400 MHz): d 0.80 (3H, d, J = 7.2 Hz), 0.81 (3H, d, J = 6.8 Hz), 0.95 (3H, d, J = 6.8 Hz), 0.96 (3H, d, J = 6.8 Hz), 1.01 (3H, s), 1.20–1.30 (1H, m), 1.34 (3H, s), 1.47–2.08 (13H, m), 2.23 (1H, dd, J = 11.6, 13.2 Hz), 2.21–2.33 (2H, m), 2.35–2.51 (2H, m), 2.80 (1H, brs), 2.90 (1H, ddd, J = 5.6, 8.0, 11.6 Hz), 3.25 (1H, d, J = 2.4 Hz), 3.92–4.02 (1H, m), 4.93 (1H, brs); ¹³C NMR (100 MHz): d 10.9, 18.2, 18.9, 19.4, 21.4, 22.0, 22.5, 26.0, 26.1, 29.4, 30.3, 30.4, 31.4, 36.9, 38.7, 39.6, 45.8, 49.2, 52.0, 56.1, 59.3, 62.6, 62.7, 68.2, 128.3, 159.8, 204.3, 215.2; HRMS (FAB): m/z calcd for C28H43O5, 459.3110; found, 459.3109 ([M+H]⁺).

(3S,4aR,5aS,6R,8R,10bR)-6-hydroxy-8-((1R,2S,3S)-3-((1S,2R)-1-hydroxy-2,3- dimethylbutyl)-2-methylcyclopentyl)-8,10b-dimethyl-7-oxo-1,3,4,5a,6,7,8,9,10,10b-decahydro-2H-phenanthro[8a,9-b]oxiren-3-yl acetate (145)

To a stirred solution of 104 (0.0500 g, 0.0684 mmol) in CH2Cl2 (2.0 mL) and EtOH (0.5 mL)

HO

O H

H O

O OH

strophasterol D (8) (putative)

AcO

O H

H TESO

O OTES 104

AcO

O H

H HO

O OH TsOH

MeOH, rt 87%

145

was added TsOH (0.0295 g, 0.171 mmol) at room temperature. After 3 h of stirring, the mixture was quenched with satd aq NaHCO3 and extracted with CH2Cl2. The extract was washed with brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc = 2:1–1:1) to give 145 (0.0301 g, 87%) as a white solid. [a]²⁰D

–11.6 (c 0.42, CHCl3); IR: nmax 3437 (s), 1726 (m), 1649 (s), 1451 (m), 1257 (s); ¹H NMR (400 MHz): d 0.78 (3H, d, J = 6.8 Hz), 0.89 (3H, d, J = 7.2 Hz), 0.91 (3H, d, J = 6.8 Hz), 0.99 (3H, s), 0.99 (3H, d, J = 6.8 Hz), 1.32–1.42 (3H, m), 1.35 (3H, s), 1.44–1.84 (10H, m), 1.86–1.97 (2H, m), 2.02–2.15 (2H, m), 2.04 (3H, s), 2.23 (1H, dt, J = 18.9, 4.9 Hz), 2.30 (1H, dd, J = 12.0, 12.8 Hz), 2.42 (1H, ddd, J = 5.0, 9.2, 18.6 Hz), 2.90 (1H, brs), 3.24 (1H, d, J = 2.8 Hz), 3.45 (1H, dd, J = 3.6, 6.8 Hz), 4.89 (1H, brs), 4.98 (1H, tt, J = 5.4, 11.1 Hz); ¹³C NMR (100 MHz):

d 10.0, 16.8, 19.3, 20.3, 21.3, 21.6, 22.0, 22.3, 23.8, 26.4, 26.6, 28.6, 29.1, 31.7, 35.1, 36.7, 39.6, 42.6, 45.6, 48.0, 50.8, 59.3, 62.2, 62.9, 70.5, 73.2, 128.2, 159.4, 170.2, 205.4; HRMS (FAB): m/z calcd for C30H47O6, 503.3373; found, 503.3377 ([M+H]⁺).

(3S,4aR,5aR,8R,10bR)-8-((1R,2S,3S)-3-((R)-2,3-dimethylbutanoyl)-2-methylcyclopentyl)-

8,10b-dimethyl-6,7-dioxo-1,3,4,5a,6,7,8,9,10,10b-decahydro-2H-phenanthro[8a,9-b]oxiren-3-yl acetate (146)

To a stirred mixture of 145 (30.1 mg, 59.7 µmol) and satd aq NaHCO3 (0.5 mL) in CH2Cl2

(2.0 mL) were successively added AZADOL (0.9 mg, 6.0 µmol), KBr (7.1 mg, 60.0 µmol), and 8% NaOCl aq (0.34 mL, 239.0 µmol) at room temperature. After 3 h of stirring, the mixture was quenched with satd aq Na2S2O3 and extracted with CH2Cl2. The extract was washed with brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column

AZADOL, NaOCl KBr, NaHCO₃ CH₂Cl₂, H₂O, rt

61% ^AcO

O H

H

O O

O

146 AcO

O H

H

O OTES

HO

145

chromatography (hexane/EtOAc = 1:1) to give 146 (18.1 µg, 61%) as a white solid. [a]²⁰D 64.0 (c 0.62, CHCl3); IR: nmax 1734 (s), 1707 (s), 1243 (s); ¹H NMR (600 MHz): d 0.84 (3H, d, J = 6.6 Hz), 0.91 (3H, d, J = 6.6 Hz), 0.98 (3H, d, J = 7.2 Hz), 0.99 (3H, d, J = 6.0 Hz), 1.04 (3H, s), 1.29 (3H, s), 1.42–1.50 (1H, m), 1.56–1.66 (3H, m), 1.70–1.82 (2H, m) 1.87–2.01 (5H, m), 2.06 (3H, s), 2.10 (1H, dt, J = 14.2, 5.0 Hz), 2.15–2.26 (2H, m), 2.33–2.43 (3H, m), 2.56 (1H, ddd, J = 5.3, 8.9, 20.3 Hz), 2.63 (1H, q, J = 8.6 Hz), 3.46 (1H, s), 4.99 (1H, tt, J = 5.4, 11.2 Hz);

13C NMR (150 MHz): d 12.6, 18.6, 19.2, 21.0, 21.2, 21.5, 22.5, 23.2, 26.4, 27.5, 29.2, 30.0, 30.1, 30.5, 34.6, 37.0, 41.5, 46.3, 47.9, 52.1, 60.8, 62.9, 64.4, 70.1, 126.5, 170.1, 171.8, 193.0, 198.2, 216.7; HRMS (FAB): m/z calcd for C30H43O6, 499.3060; found, 459.3065 ([M+H]⁺).

(3S,4aR,5aS,6S,8R,10bR)-8-((1R,2S,3S)-3-((R)-2,3-dimethylbutanoyl)-2- methylcyclopentyl)-3,6-dihydroxy-8,10b-dimethyl-1,3,4,6,8,9,10,10b-octahydro-2H-phenanthro[8a,9-b]oxiren-7(5aH)-one (144)

To a stirred mixture of 146 (17.0 mg, 34.1 µmol) in MeOH (0.5 mL) were successively added NaBH4 (1.3 mg, 34.1 µmol) at 0 ºC. After 10 min of stirring, the mixture was quenched with satd aq NaHCO3 and extracted with EtOAc The extract was washed with brine, dried (MgSO4),

HO

O H

H

O OH

O

strophasterol C (2 steps 60%) AcO

O H

H

O O

O

146

NaBH₄ MeOH, 0 ºC

AcO

O H

H

O OH

O

147

HO

O H

H

O OH

O

144 (strophasterol D) (2 steps 15%)

+

Mg, MeOH 50 ºC

and concentrated in vacuo to give 147 as a white amorphous solid, which was then taken up in MeOH (0.5 mL). To the solution was added Mg (1.9 mg, 76.2 µmol) at 50 ºC while stirring.

After 2 h the mixture was quenched with satd aq NaHCO3 and extracted with EtOAc. The extract was successively washed with water and brine, dried (MgSO4), and concentrated in vacuo. The residue was purified by silica gel column chromatography (CH2Cl2/MeOH = 15:1) to give strophasterol C (9.3 mg, 60% form 146) white amorphous solid and 144 (2.4 mg, 15%

from 137) as a white amorphous solid. Physical data of 144: [a]²⁰D –18.3 (c 0.14, MeOH); IR:

nmax 3469 (s), 1703 (s), 1642 (m); ¹H NMR (400 MHz): d 0.84 (3H, d, J = 6.8 Hz), 0.91 (3H, d, J = 6.8 Hz), 0.96–1.01 (9H, m), 1.17 (3H, s), 1.42–1.75 (7H, m), 1.76–1.90 (4H, m), 2.01–

2.12 (3H, m), 2.14–2.26 (3H, m), 2.33–2.47 (2H, m), 2.62 (1H, q, J = 8.3 Hz), 3.35 (1H, b, J = 2.0 Hz), 3.95–4.05 (1H, m), 4.53 (1H, d, J = 2.0 Hz), 4.86 (1H, brs); ¹³C NMR (100 MHz): d 12.7, 18.7, 19.1, 20.6, 21.47, 21.54, 22.3, 26.9, 29.2, 29.3, 30.1, 30.3, 31.2, 37.1, 38.8, 40.6, 46.1, 47.4, 52.1, 60.4, 61.1, 62.2, 64.9, 68.1, 127.9, 159.2, 207.0, 216.7; HRMS (FAB): m/z calcd for C28H43O5, 459.3110; found, 459.3106 ([M+H]⁺).

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