セレノ化糖を用いた蛋白質結晶構造解析に関する基盤研究

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Title

セレノ化糖を用いた蛋白質結晶構造解析に関する基盤研究(

_{本文(Fulltext) )}

Author(s)

島袋, 隼平

Report No.(Doctoral

Degree)

博士(農学) 甲第670号

Issue Date

2017-03-13

Type

博士論文

Version

ETD

URL

http://hdl.handle.net/20.500.12099/56218

※この資料の著作権は、各資料の著者・学協会・出版社等に帰属します。

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ࢭࣞࣀ໬⢾ࢆ⏝࠸ࡓ⺮ⓑ㉁⤖ᬗᵓ㐀ゎᯒ࡟㛵ࡍࡿᇶ┙◊✲

2016 ᖺ

ᒱ㜧኱Ꮫ኱Ꮫ㝔㐃ྜ㎰Ꮫ◊✲⛉

⏕≀㈨※⛉Ꮫ

(ᒱ㜧኱Ꮫ)

ᓥ⿄

㞙ᖹ

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ࢭࣞࣀ໬⢾ࢆ⏝࠸ࡓ⺮ⓑ㉁⤖ᬗᵓ㐀ゎᯒ࡟㛵ࡍࡿᇶ┙◊✲

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␎

␎ྕ⾲

ᮏㄽᩥ࡟࠾࠸࡚௨ୗ࡟♧ࡍࠊ┬␎⾲グࢆ⏝࠸ࡓࠋ Ac : acetyl

BDA : benzaldehyde dimethylacetal Bn : benzyl

BOM : benzyloxymethyl Bz : benzoyl

Bzld : benzylidene

CSA : dl-10-camphorsulfonic acid DIEA : N,N-diisopropylethylamine DMAP : 4-dimethylaminopyridine DMA : N,N-dimethylacetamide DMC : 2-chloro-1,3-dimethyl-2-imidazolinium chloride DMF : N,N-dimethylformamide 2,2-DMP : 2,2-dimethoxypropane DMP : Dess-Martin periodinane Fuc : fucose Gal : galactose GalN : galactosamine GlcN : glucosamine

HEPES : 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid HPLC : high performance liquid chromatography

Man : mannose

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2 NBS : N-bromosuccinimide Me : methyl PG : protective group PMB : p-methoxybenzyl Pyr : pyridine TBA : tetra-n-butylammonium TBME : methyl tert-butyl ether TBDPS : tert-butyldiphenylsilyl TEA : triethylamine

TEOA : triethylorthoacetate TFA : trifluoroacetic acid

Tf2O : trifluoromethanesulfonic anhydride

THF : tetrahydrofuran

TMOA : trimethylorthoacetate Tol : 4-methylbenzoyl

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3

┠

┠ḟ

⥴ㄽ 5 ➨୍㒊 ࢭࣞࣀ໬ࣇࢥ࣮ࢫㄏᑟయ⩌ࡢྜᡂ࠾ࡼࡧࡑࡢᛂ⏝ ➨୍❶ ࢭࣞࣀ໬ࣇࢥ࣮ࢫㄏᑟయࡢྜᡂ ➨୍⠇ ศᏊタィ࡜ྜᡂᡓ␎ 9 ➨஧⠇ α-ཬࡧ β-࣓ࢳࣝࢭࣞࣀࣇࢥ࣮ࢫࡢྜᡂ 12 ➨୕⠇ 2-࣓ࢳࣝࢭࣞࣀࣇࢥ࣮ࢫࡢྜᡂ 14 ➨ᅄ⠇ 3-࣓ࢳࣝࢭࣞࣀࣇࢥ࣮ࢫࡢྜᡂ 18 ➨஬⠇ 4-࣓ࢳࣝࢭࣞࣀࣇࢥ࣮ࢫࡢྜᡂ 23 ➨஧❶ ࢭࣞࣥㄏᑟయࢆ⏝࠸ࡓ X ⥺ඹ⤖ᬗᵓ㐀ゎᯒ࠾ࡼࡧ⤖ྜぶ࿴ᛶヨ㦂 ➨୍⠇ ࣇࢥ࣮ࢫࣞࢡࢳࣥ AOL ࡢ❧యᵓ㐀ゎᯒ 24 ➨஧⠇ AOL ࡜ࡢぶ࿴ᛶ ᐃ 26 ➨୍㒊ࡲ࡜ࡵ 28

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4 ➨஧㒊 ⢾⺮ⓑ㉁ࡢX ⥺⤖ᬗᵓ㐀ゎᯒࡢ㎿㏿໬ࢆᣦྥࡋࡓࢭࣞࣀ໬⢾ࡢ㛤Ⓨ ➨୍❶ ◊✲⫼ᬒ 29 ➨஧❶ ศᏊタィ 32 ➨୕❶ ᶆ㆑ศᏊࡢྜᡂ 33 ➨ᅄ❶ Endoglycosidase ࢆ⏝࠸ࡓ⢾㌿⛣཯ᛂࡢ᳨ウ 36 ➨஧㒊ࡲ࡜ࡵ 41 ⥲ᣓ 42 ᐇ㦂ࡢ㒊 43 ㅰ㎡

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5

⥴

⥴ㄽ

⏕࿨⌧㇟ࡣ᰾㓟ࠊ⺮ⓑ㉁ࠊ⢾㙐࡞࡝ࡢ⏕య㧗ศᏊࡀᶵ⬟ࡍࡿࡇ࡜࡟ࡼࡗ࡚Ⓨ⌧ࡋ࡚࠸ࡿࠋ ࡇࢀࡽࡢ⏕య㧗ศᏊࡀࡑࡢᶵ⬟ࢆⓎ⌧ࡍࡿ࡟࠶ࡓࡗ࡚ࠊࡑࡢከࡃࡣ❧యᵓ㐀࡟ᇶ࡙࠸ࡓศ Ꮚㄆ㆑࡟ᇶ࡙ࡃ」ྜయᙧᡂࢆ㛤ጞẁ㝵࡟᭷ࡋ࡚࠸ࡿ1,2,3ࠋࡑࡢࡓࡵ⏕య㧗ศᏊࡢᶵ⬟Ⓨ⌧ᶵ ᵓࢆศᏊ࡛ࣞ࣋ࣝ⌮ゎࡍࡿࡓࡵ࡟ࡣࡑࡢࡼ࠺࡞」ྜయࡢ❧యᵓ㐀᝟ሗࡢྲྀᚓࡀᴟࡵ࡚㔜せ ࡛࠶ࡿࠋࡲࡓࠊࡇࡢࡼ࠺࡞ᶵ⬟Ⓨ⌧ᶵᵓࡢゎ᫂ࡣ⏕࿨⌧㇟ࡢ⌮ゎ࡟␃ࡲࡽࡎࠊ≉ᐃࡢ⌧㇟ ࢆไᚚ࡛ࡁࡿ໬ྜ≀ࡢྜ⌮ⓗ࡞タィࢆྍ⬟࡜ࡋࠊ๰⸆ࡢ㎿㏿໬࡞࡝ࡀぢ㎸ࡲࢀࡿࠋ ⺮ⓑ㉁ࡢ❧యᵓ㐀ゎᯒ࡟ࡣ᰾☢Ẽඹ㬆ࡸ㟁Ꮚ⥺ࢆ⏝࠸ࡓࡶࡢ࡞࡝ࡀ࠶ࡿࠋ࡞࠿࡛ࡶࠊ㟁 Ꮚ࡟ࡼࡿX ⥺ࡢᅇᢡ⌧㇟ࢆ฼⏝ࡋ࡚ࠊ⺮ⓑ㉁⤖ᬗෆ㒊࡛ࡢཎᏊ㓄ิࢆ᫂ࡽ࠿࡟ࡍࡿ X ⥺⤖ ᬗᵓ㐀ゎᯒἲࡣ᭱ࡶヲ⣽࡟ࡑࡢ❧యᵓ㐀ࢆỴᐃࡍࡿࡇ࡜ࡀ࡛ࡁࡿᡭἲ࡛࠶ࡿࠋࡋ࠿ࡋࠊX ⥺ ࡢ᳨ฟჾࡣἼ㛗࡜᣺ᖜࡢࡳࡋ࠿グ㘓ࡍࡿࡇ࡜ࡀ࡛ࡁࡎࠊཎᏊࡢ఩⨨᝟ሗࢆ▱ࡿࡢ࡟ᚲせ࡞ ఩┦ࢆ᳨ฟࡍࡿࡇ࡜ࡀ࡛ࡁ࡞࠸ࡢ࡛ఱࡽ࠿ࡢ᪉ἲ࡛఩┦ࢆ᥎ᐃࡍࡿᚲせࡀ࠶ࡿࠋྂࡃ࠿ࡽ ⾜ࢃࢀ࡚࠸ࡿ఩┦Ỵᐃἲ࡜ࡋ࡚ࠊ⺮ⓑ㉁ࢆᵓᡂࡍࡿཎᏊ࡜ẚ㍑ࡋ࡚㟁Ꮚᐦᗘࡀ኱ࡁࡃ␗࡞ ࡿỈ㖟ࡸⓑ㔠ࠊ㖄࡞࡝ࡢ㔜ཎᏊࢆ఩┦Ỵᐃࡢ㝿ࡢ┠༳࡜ࡋ࡚⺮ⓑ㉁࡟ᑟධࡋࠊᶆ㆑ࡋࡓ⤖ ᬗ࡜ࢿ࢖ࢸ࢕ࣈ⤖ᬗ࡜ࡢᅇᢡᙉᗘࢹ࣮ࢱࢆẚ㍑ࡍࡿࡇ࡜࡛⾜࠺㔜ཎᏊከ㔜ྠᆺ⨨᥮ἲ(MIR ἲ)ࡀ࠶ࡿ(Fig. 1)ࠋࡑࡢ௚࡟ࡶࠊ㏆ᖺࠊἼ㛗ྍኚ࡞ࢩࣥࢡࣟࢺࣟࣥᨺᑕගࡀ฼⏝ྍ⬟࡟࡞ࡗ ࡓࡇ࡜ࡸ␗ᖖᩓ஘ཎᏊࡢ୍ࡘ࡛࠶ࡿࢭࣞࣥཎᏊࢆ㑇ఏᏊᕤᏛⓗᡭἲ࡟ࡼࡾ⺮ⓑ㉁࡟ᑟධࡍ ࡿࡇ࡜ࡀྍ⬟࡟࡞ࡗࡓࡇ࡜࠿ࡽከἼ㛗␗ᖖศᩓἲ(MAD ἲ)ࡀ⾜ࢃࢀࡿࡼ࠺࡟࡞ࡗࡓࠋMAD ἲࡣ1990 ᖺึ㢌 Graves ࡽ࡟ࡼࡿ࢖ࣥࢱ࣮ࣟ࢖࢟ࣥ 1α4ࡸHendrickson ࡽ࡟ࡼࡿࣜ࣎ࢡࣞ࢔

1_{Sok, D.; Doores, K. J.; Briney, B.; Le, K. M.; Saye-Francisco, K. L.; Ramos, A.; Kulp, D. W.;}

Jean-Philippe, J.; Menis, S.; Wickramasinghe, L.; Seaman, M. S.; Schief, W.; Wilson, I. A.; Poignard, P.; Burton, D. R. Sci. Transl. Med. 2014, 6, 236.

2_{Stenmark, P.; Dupuy, J.; Imamura, A.; Kiso, M.; Stevens, R. C. PLoS Pathogens 2008, 4,}

e1000129.

3_{Kato, K.; Ishiwa, A. Trop. Med. Health 2015, 43, 41.}

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6

࣮ࢮ H5ࡢゎᯒ࡞࡝࠿ࡽ฼⏝ࡉࢀጞࡵࡓᡭἲ࡛࠶ࡾࠊ」ᩘࡢ㔜ཎᏊᾐₕ⤖ᬗࢆᚲせ࡜ࡍࡿ

MIR ἲ࡟ẚ࡭⡆౽࠿ࡘ㎿㏿࡛࠶ࡿࠋࡑࡋ࡚ MAD ἲࡀሗ࿌ࡉࢀ࡚௨㝆ࠊX ⥺⤖ᬗᵓ㐀ゎᯒἲ

࡟ࡼࡿ⺮ⓑ㉁ࡢᵓ㐀Ỵᐃᩘࡣ1990 ᖺࢆቃ࡟ᛴ⃭࡟ቑຍࡋ࡚࠸ࡿࠋ

Fig.1 MIR ἲ࡜ MAD ἲ࡟࠾ࡅࡿ㔜ཎᏊᶆ㆑ࡢᴫ␎ᅗ

ࡋ࠿ࡋࠊMAD ἲ࡟ࡶ࠸ࡃࡘ࠿ㄢ㢟ࡀᏑᅾࡍࡿࠋ౛࠼ࡤࠊࢭࣞࣀ࣓ࢳ࢜ࢽࣥ(SeMet)ࢆ᭷ࡍ ࡿ㠀ኳ↛ᆺ⺮ⓑ㉁ࢆ኱⭠⳦࡟⏘⏕ࡉࡏࡿ㝿ࠊ࣓ࢳ࢜ࢽࣥせồ኱⭠⳦ᰴ࠶ࡿ࠸ࡣ㓝ẕࢆ L-ࢭ ࣞࣀ࣓ࢳ࢜ࢽࣥྵ᭷ᇵᆅ୰࡛ᇵ㣴ࡍࡿᚲせࡀ࠶ࡿࡇ࡜ࡀᣲࡆࡽࢀࡿࠋࡑࢀ࡜࠸࠺ࡢࡶࠊࢭ ࣞࣥཎᏊࡢẘᛶࡢࡓࡵ࡟⺮ⓑ㉁⏘⏕⣽⬊ࡀ༑ศ࡟⏕⫱ࡏࡎࠊࢧࣥࣉࣝㄪ〇ࡢ㛗ᮇ໬ࡀᘬࡁ ㉳ࡇࡉࢀࡿሙྜࡀ࠶ࡿࠋࡲࡓࠊ◲㯤ཎᏊ࡜ࢭࣞࣥཎᏊ࡛ࡣ⤖ྜゅࡸࣇ࢓ࣥࢹ࣮ࣝ࣡ࣝࢫ༙ ᚄ࡞࡝ࡢ≀⌮໬Ꮫⓗ࡞ᛶ㉁ࡀ␗࡞ࡿࡓࡵࠊࢭࣞࣥཎᏊᑟධ࡟ࡼࡿ❧యᵓ㐀ࡢኚ໬ࡸࠊ⺮ⓑ ㉁ࡢ⁐ゎᛶࡸ⤖ᬗᛶࡢపୗ࡞࡝ࡀᘬࡁ㉳ࡇࡉࢀ⤖ᬗ໬ࡀᅔ㞴࡜࡞ࡿሙྜࡀ࠶ࡿࠋࡇࡢࡼ࠺ ࡞ၥ㢟࡟ᑐࡍࡿゎỴ⟇ࡢ୍ࡘ࡜ࡋ࡚⺮ⓑ㉁ࢆࢭࣞࣥᶆ㆑ࡍࡿࡢ࡛ࡣ࡞ࡃࠊ⺮ⓑ㉁࡟≉␗ⓗ ࡟⤖ྜࡍࡿࣜ࢞ࣥࢻࢆࢭࣞࣥᶆ㆑ࡋࠊࢭࣞࣀ໬ࣜ࢞ࣥࢻ-⺮ⓑ㉁」ྜయ࡜ࡋ࡚⤖ᬗᵓ㐀ゎᯒ Biochemistry 1990, 29, 2670.

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7 ࡬฼⏝ࡍࡿࡇ࡜ࡀ⪃࠼ࡽࢀࡿࠋ ࡇࢀࡲ࡛࡟ࠊButs ࡽ6_{ࢆጞࡵ࡜ࡋ࡚ࠊࢭࣞࣀ໬⢾ࢆ⏝࠸ࡓ⢾ㄆ㆑⺮ⓑ㉁ࡢ}_{X ⥺⤖ᬗᵓ㐀ゎ} ᯒࡀ࠸ࡃࡘ࠿ሗ࿌ࡉࢀ࡚࠸ࡿ7,8,9ࠋࡲࡓࠊᙜ◊✲ᐊࡢ㕥ᮌࡣ࢞ࣛࢡࢺ࣮ࢫࡲࡓࡣࢢࣝࢥ࣮ࢫ ࡢ 6 ఩Ỉ㓟ᇶࢆ࣓ࢳࣝࢭࣞࣀ(MeSe)ᇶ࡛⨨᥮ࡋࡓࢭࣞࣥᶆ㆑ࣛࢡࢺ࣮ࢫࢆྜᡂࡋࠊࡉࡽ࡟ ࡑࢀࢆ⏝࠸࡚࢞ࣞࢡࢳࣥ 9NCRD ࡢ❧యᵓ㐀Ỵᐃࢆ⾜࠸ࢭࣞࣥྵ᭷஧⢾ㄏᑟయࡢ X ⥺⤖ᬗ ᵓ㐀ゎᯒ࡟࠾ࡅࡿ᭷⏝ᛶࢆぢฟࡋ࡚࠸ࡿ(Fig. 2)10_{ࠋࡲࡓࠊࡇࡢ◊✲࡟࠾࠸࡚ࢭࣞࣥཎᏊࡢᑟ} ධ఩⨨࡟ࡼࡾ⺮ⓑ㉁࡜ࡢඹ⤖ᬗ໬ࡢྍྰࡀᕥྑࡉࢀࡿࡇ࡜ࡀ᫂ࡽ࠿࡜࡞ࡗࡓ(Fig. 2)ࠋ Fig. 2 ࢞ࣞࢡࢳࣥ 9NCRD ࡜࣓ࢳࣝࢭࣞࣀࣛࢡࢺ࣮ࢫ」ྜయࡢ❧యᵓ㐀 ࡇࡢࡇ࡜࠿ࡽࠊࢭࣞࣀ໬⢾ࢆ⏝࠸ࡓ X ⥺⤖ᬗᵓ㐀ゎᯒ࡟ࡳࡽࢀࡿၥ㢟Ⅼ࡜ࡋ࡚ᇶ㉁ㄆ㆑ ᶵᵓࡀ୙᫂࡞⺮ⓑ㉁࡬ࡢࢭࣞࣀ໬⢾ࡢ฼⏝࡟ࡣࠊணࡵㄪ〇ࡋࡓ໬ྜ≀ࡀᇶ㉁࡜ࡋ࡚ㄆ㆑ࡉ ࢀ࡞࠸ྍ⬟ᛶࡀ࠶ࡿࡇ࡜ࡀᣲࡆࡽࢀࡿࠋࡲࡓࠊ㏆ᖺࠊ⏺㠃άᛶ๣࡜ࡋ࡚ࢭࣞࣀ໬⢾ࢆ⏝࠸

6_{Buts, L.; Loris, R.; Genst, E. D.; Oscarson, S.; Lahmann, M.; Messens, J.; Brosens, E.; Wyns,}

L.;Greve, H. D.; Bouckaert, J. Acta Cryst. 2003, D59, 1012.

7_{Kostlánová, N.; Mitchell, E.P.; Lortat-Jacob, H.; Oscarson, S.; Lahmann, M.; Gilboa-Garber, N.;}

Chambat, G.; Wimmerová, M.; Imberty, A. J. Biol. Chem. 2005, 280, 27839.

8_{Houser, J.; Komarek, J.; Kostlanova, N.; Cioci, G.; Varrot, A.; Kerr, S. C.; Lahmann, M.; Balloy,}

V.; Fahy, J. V.; Chignard, M.; Imberty, A.; Wimmerova, M.; PLoS One 2013, 8, e83077.

9_{Sulák, O.; Cioci, G.; Delia, M.; Lahmann, M.; Varrot, A.; Imberty A.; Wimmerová, M. Structure}

2010, 18, 59.

10_{Suzuki, T.; Makyio, H.; Ando, H.; Komura, N.; Menjo, M.; Yamada, Y.; Imamura, A.; Ishida, H.;}

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8

ࡓ⭷⺮ⓑ㉁ࡢ❧యᵓ㐀ゎᯒ11ࡀሗ࿌ࡉࢀࡓࡀ(Fig. 3)ࠊᵓ㐀ゎᯒศ㔝࡟࠾ࡅࡿࢭࣞࣀ໬⢾฼⏝

ࡢ࡯࡜ࢇ࡝ࡀ⢾ㄆ㆑⺮ⓑ㉁࡟ᑐࡋ࡚ࡢࡳ࡛࠶ࡾỗ⏝ᛶ࡟ஈࡋ࠸ࠋࡑࡇ࡛ᮏ◊✲࡛ࡣࠊ୍ࡘ ┠ࡢၥ㢟࡟ᑐࡋ࡚ࠊᑟධ఩⨨ࡢ␗࡞ࡿࢭࣞࣀ໬⢾ࣛ࢖ࣈ࣮ࣛࣜࢆᵓ⠏ࡋࠊࡑࢀࡽࢆヨ⾜ⓗ

࡟ඹ⤖ᬗ໬࡬౪ࡍࡿࡇ࡜ࡀ᭷ຠ࡛࠶ࡿ࡜⪃࠼ࠊࣇࢥ࣮ࢫㄏᑟయ⩌ࡢྜᡂ࠾ࡼࡧ Aspergillus

oryzae lectin, AOL ࢆ⏝࠸࡚๓㏙ࡋࡓᡭἲࡢ᭷⏝ᛶࢆ➨୍㒊࡟᳨࡚ドࡍࡿࡇ࡜࡜ࡋࡓࠋ

ࡲࡓࠊ➨஧㒊࡛ࡣࢭࣞࣀ໬⢾ࢆ⏝࠸ࡓ᪂ࡓ࡞ᶆ㆑ἲ࡜ࡋ࡚ࠊ㓝⣲໬Ꮫⓗ࡞㌿⛣཯ᛂࢆ฼ ⏝ࡋࡓ⺮ⓑ㉁࡬ࡢᑟධࢆᥦ᱌ࡋ◊✲ࢆ⾜ࡗࡓࠋ

F ig . 3 Le u k o tr ie n e C 4 ྜ ᡂ 㓝 ⣲ ࡜

Dodecyl-β-D-selenomaltoside ࡜ࡢ」ྜయࡢ❧యᵓ㐀

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9

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➨୍㒊

ࢭࣞࣀ໬ࣇࢥ࣮ࢫㄏᑟయ⩌ࡢྜᡂ࠾ࡼࡧࡑࡢᛂ⏝

➨୍❶ ࢭࣞࣀ໬ࣇࢥ࣮ࢫㄏᑟయࡢྜᡂ

➨୍⠇ ศᏊタィ࡜ྜᡂᡓ␎

ᮏ◊✲࡛ࡣࢭࣞࣀ໬⢾ࣛ࢖ࣈ࣮ࣛࣜᵓ⠏ࡢ㝿ࡢࣔࢹࣝ໬ྜ≀࡜ࡋ࡚ࠊᵓ㐀ⓗ࡞༢⣧ࡉࡸࠊ ⬇Ⓨ⏕12࣭ศ໬13࣭⣽⬊ㄆ㆑14࣭⒴໬15,16࣭⅖⑕17,18࡞࡝ࡢ⏕࿨⌧㇟࡟࠾ࡅࡿ㔜せᛶࢆ⪃៖ࡋ ࣇࢥ࣮ࢫࢆ㑅ᢥࡋࡓࠋ⢾ศᏊ࡬ࡢࢭࣞࣥཎᏊࡢᑟධࡣࠊࡇࢀࡲ࡛࡟ᙜ◊✲ᐊ࡛ሗ࿌ࡋ࡚࠸ ࡿᡭἲ࡟๎ࡿࡇ࡜࡜ࡋࡓࠋࡲࡓࠊࢭࣞࣀ࣮ࣝ(RSeH)ࡣᐜ᫆࡟㓟໬ࡉࢀࢪࣞࢭࢽࢻ(RSeSeR) ࡜࡞ࡿࡓࡵࠊ࢔ࣝ࢟ࣝᇶ࡛ಖㆤࡍࡿࡇ࡜࡜ࡋࡓࠋࡲࡓࠊ⺮ⓑ㉁࡜ࡢ┦஫స⏝࡟୚࠼ࡿᙳ㡪 ࢆ᭱ᑠ㝈࡜ࡍࡿࡓࡵMe ᇶ࡛ಖㆤࡋࡓࡶࡢࢆ᭱⤊┠ⓗ≀࡟タᐃࡋࡓ(Fig. 4)ࠋ Fig. 4 ࢔ࣀ࣐࣮఩࡟ᑐࡍࡿࢭࣞࣥཎᏊࡢᑟධࡣࠊᙜ◊✲ᐊ࡟࠾࠸࡚㐣ཤ࡟ሗ࿌ࡉࢀࡓΰྜࢭࣞ

12_{Solter, D.; Knowles, B.B. Proc. Natl Acad. Sci. USA 1978, 75, 5565.}

13_{Gringhuis, S. I. ; Kaptein, T. M.; Wevers, B. A.; van der Vlist, M.; Klaver, E. J.; van Die, I.;}

Vriend , L. E. M.; de Jong, M. A.W. P.; Geijtenbeek, T. B.H. Nat. Commun. 2014, 5, 5074.

14_{Li, Y.-L.; Wu, G.-Z.; Zeng, L.; Dawe, G. S.; Sun, L.; Loers, G.; Tilling, T.; Cui, S.-s.; Schachner,}

M.; Xiao, Z.-C. FEBS Lett. 2009, 583, 703.

15_{Kannagi, R. Glycoconj. J. 1997, 14, 577.}

16_{Kim, Y. J.; Varki, A. Glycoconj. J. 1997, 14, 569.}

17_{Flogel, M.; Lauc, G.; Gornik, I.; Macek, B. Clin. Chem. Lab. Med. 1998, 36, 99.} 18_{Gornik, I.; Maravic, G.; Dumic, J.; Flogel, M.; Lauc, G. Clin. Biochem. 1999, 32, 605.}

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10 ࣀ࢔ࢭࢱ࣮ࣝࡢ㌿⛣཯ᛂ19ࢆ฼⏝ࡍࡿࡇ࡜࡟ࡼࡾࠊྠ୍ࡢ୰㛫య࠿ࡽ࢔ࣀ࣐࣮␗ᛶయࡢྜᡂ ࢆ⡆౽࡟⾜࠼ࡿ࡜⪃࠼ࡓࠋࡲࡓࠊ⦰ྜ᫬࡟࠾ࡅࡿ㞄᥋ᇶ㛵୚ࢆ᤼㝖ࡍࡿࡓࡵ࡟ 2 ఩Ỉ㓟ᇶ ࢆ࢔ࣝ࢟ࣝ⣔ಖㆤᇶ࡛࠶ࡿPMB ᇶ࡛ಖㆤࡍࡿࡇ࡜࡜ࡋࡓ(Fig. 5)؛ ࡲࡓࠊࡇࡇ࡛ Bn ᇶ࡜ࡋ ࡞࠿ࡗࡓࡢࡣࠊࢭࣞࣥཎᏊࡀPd ࢆ⿕ẘࡋỈ⣲ῧຍ࡟ࡼࡿ⬺ಖㆤࡀ⾜࠼࡞࠸ࡓࡵ࡛࠶ࡿ20ࠋ Fig. 5 ⢾ࢾࢡࣞ࢜ࢳࢻࢆ㝖ࡁ⮬↛⏺࡟Ꮡᅾࡍࡿ࡯ࡰࡍ࡭࡚ࡢࣇࢥ࣮ࢫࡣ α-ࢢࣜࢥࢩࢻ⤖ྜࢆ௓ ࡋ࡚௚ࡢ⢾࡜⤖ྜࡋ࡚࠸ࡿࡓࡵࠊ2 ఩ࠊ3 ఩ࠊ4 ఩⨨᥮యࡢ࢔ࣀ࣐࣮఩ࡢ❧య໬Ꮫࡣ඲࡚ α ࡟⤫୍ࡋࡓ(Fig. 4)ࠋ2 ఩ࠊ3 ఩ࠊ4 ఩࡬ࡢࢭࣞࣥཎᏊࡢᑟධࡣࠊࢭࣞࣀࢺࣝ࢜࢖ࣝ㓟↓Ỉ≀21,22 ࡢάᛶ໬࡜ࡑࢀ࡟⥆ࡃồ㟁ᏊⅣ⣲࡬ࡢồ᰾⨨᥮཯ᛂࡲࡓࡣࢭࣞࣀࢺࣝ࢜࢖ࣝ㓟࣒࢝ࣜ࢘23 ࡟ࡼࡿồ᰾⨨᥮཯ᛂ࡟ࡼࡾᑟධࢆ⾜࠺ࡇ࡜࡜ࡋࡓ(Fig. 6)ࠋࡲࡓࠊࢭࣞࣀ࢔ࢩ࣮ࣞࢺ࢔ࢽ࢜ ࣥ(RCOSe-)ࡸࢭࣞࣀ࣮ࣛࢺ࢔ࢽ࢜ࣥ(RSe-)ࡣࠊ㓟⣲ศᏊ࡟ࡼࡾᐜ᫆࡟㓟໬ࡉࢀࣛࢪ࢝ࣝ୰㛫 యࢆ⤒࡚ࢪࢭࣞࢽࢻయ(RCOSeSeCOR, RSeSeR)࡜࡞ࡿࡓࡵࠊᮏ◊✲࡛ࡣࠊࢭࣞࣀ࣋ࣥࢰ࢚࣮ ࢺ໬࠾ࡼࡧࢭࣞࣥཎᏊࡢ࢔ࣝ࢟ࣝ໬ࡢ㝿ࠊࢭࣞࣀ࢔ࢽ࢜ࣥࡢᏳᐃ໬ࡢࡓࡵ࡟ᑐ࢝ࢳ࢜ࣥ※ ࡜ࡋ࡚DIEA ࡲࡓࡣ Cs2CO3࡞࡝ࡢሷᇶࢆຍ࠼࡚࠸ࡿࠋ

19_{Suzuki, T.; Komura, N.; Imamura, A.; Ando, H.; Ishida, H.; Kiso, M. Tetrahedron Lett. 2014, 55,}

1920.

20_{Ἑྜ⏤⨾Ꮚ,}_{ᒱ㜧኱Ꮫ኱Ꮫ㝔ᕤᏛ◊✲⛉ಟኈㄽᩥ}_2007.

21_{Ishihara, H.; Sato, S.; Hirabayashi, Y. Bull. Chem. Soc. Jpn. 1977, 50, 3007.} 22_{Kawai, Y.; Ando, H.; Ozeki, H.; Koketsu, M.; Ishihara, H. Org. Lett. 2005, 7, 4653.} 23_{Ishihara, H.; Matsunami, N.; Yamada, Y. Synthesis 1987, 4, 371.}

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11

Fig. 6

2-MeSe-Fuc 2 ࡢྜᡂ࡛ࡣࠊGal 3 ఩࡜ Me-Fuc 2 ఩ࡢ❧య໬Ꮫⓗ࡞⎔ቃࡀ㢮ఝࡋ࡚࠸ࡿࡇ

࡜࠿ࡽࠊᙜ◊✲ᐊ࡟࠾࠸࡚㐣ཤ࡟⾜ࢃࢀࡓGal3 ఩ࡢࣁࣟࢤࣥ໬ࢆ⤒ࡓ࣊ࢸࣟཎᏊᑟධࢆ㋃

くࡍࡿࡇ࡜࡜ࡋࡓ(Fig. 7)24_ࠋ

Fig. 7

ࡲࡓࠊ3-MeSe-Fuc 3 ࡢྜᡂ࡛ࡣࠊ཯ᛂᕤ⛬ᩘࢆ⪃៖ࡋ Bundle ࡽ25_{࡟ࡼࡾሗ࿌ࡉࢀ࡚࠸ࡿ}

Methyl 4-benzoyl-3-bromo-3,6-dideoxyguloside ࢆ๓㥑య࡜ࡋࡓࠋ4-MeSe-Fuc 4 ࡢྜᡂ࡛ࡣࠊ3

ࣈࣟࣔయࢆㄪ〇ࡍࡿ㝿࡟ᚓࡽࢀࡿMethyl 3-benzoyl-4-bromo-4,6-dideoxyglucoside ࢆ๓㥑య࡜

ࡋࡓ(Fig 8)ࠋ

Fig. 8

24_{ᯘ ▱⾰㤶,}_{ᒱ㜧኱Ꮫ኱Ꮫ㝔ᛂ⏝⏕≀⛉Ꮫ◊✲⛉ಟኈㄽᩥ}_2011.

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12

➨

➨஧⠇

α-ཬࡧ β-࣓ࢳࣝࢭࣞࣀࣇࢥ࣮ࢫࡢྜᡂ

ྜᡂᡓ␎࡛㏙࡭ࡓࡼ࠺࡟ࠊ࣓ࢳࣝࢭࣞࣀࣇࢥࢩࢻྜᡂࡢ㘽࡜࡞ࡿ࢔ࣀ࣐࣮఩࡬ࡢMeSe ᇶ ࡢᑟධࡣࠊᮏ◊✲ᐊࡢ㕥ᮌࡀ㛤Ⓨࡋࡓΰྜࢭࣞࣀ࢔ࢭࢱ࣮ࣝ࡜⢾࢖࣑ࢹ࣮ࢺࢆ⏝࠸ࡿ࢔ࢭ ࢱ࣮ࣝ஺᥮཯ᛂ19࡟ࡼࡾ⾜࠺ࡇ࡜࡜ࡋࡓࠋᕷ㈍ࡢL-Fuc 5 ࢆฟⓎ≀㉁࡜ࡋ࡚ 9 ẁ㝵ࡢ཯ᛂࢆ ⤒࡚࢖࣑ࢹ࣮ࢺయ626ࢆᚓࡓ؛⥆࠸࡚ㄪ〇ࡋࡓࣇࢥ࣮ࢫࢻࢼ࣮6 ࠾ࡼࡧ BOM ࣓ࢳࣝࢭࣞࢽࢻ

719ࢆ⏝࠸ؚ࡚TMSOTfࠊMS-AW300 Ꮡᅾୗࠊࢭࣞࣀ໬ࢆ⾜ࡗࡓ(Scheme 1, Table 1)؛ࡇࡢ࡜

ࡁࠊ⁐፹ຠᯝ࡟ࡼࡿα 㑅ᢥⓗࢢࣜࢥࢩࣝ໬ࢆᮇᚅࡋࠊ཯ᛂ⁐፹࡜ࡋ࡚ ether/CH2Cl2ࡢΰྜ⁐

፹ࢆ⏝࠸ࡓ27ࠋ

Scheme 1 Table 1

26_{Hara, A.; Imamura, A.; Ando, H.; Ishida, H.; Kiso, M.; Molecules 2013, 19, 414.} 27_{Ishiwata, A.; Munemura, Y.; Ito, Y. Tetrahedron 2008, 64, 92.}

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13 Entry1 ࡛ࡣ CPME-CH2Cl2ࢆ⏝࠸࡚཯ᛂࢆ⾜ࡗࡓ࡜ࡇࢁࠊ┠ⓗ≀ 8α ࡀ 30%ᚓࡽࢀࡓࠋࡇࡢ ࡜ࡁࠊ࣑࣊࢔ࢭࢱ࣮ࣝࡀ 51%⏕ᡂࡋࡓࠋࡇࡢ⤖ᯝࡣࠊ࢔ࢡࢭࣉࢱ࣮ࡀࢻࢼ࣮࡟ᑐࡋ࡚ᑡ㔞 ࡛࠶ࡗࡓࡓࡵࠊ࢔ࢡࢭࣉࢱ࣮࡜཯ᛂࡍࡿ๓࡟ΰධࡋࡓỈ࡜཯ᛂࡋࡓ⤖ᯝ࡜⪃࠼ࡓࠋࡑࡢࡓ ࡵEntry 2 ࡛ࡣ࢜࢟ࢯ࢝ࣝ࣋ࢽ࣒࢘࢖࢜ࣥ࡜ࢭࣞࣀ࢔ࢭࢱ࣮ࣝ 7 ࡢ᥋ゐ☜⋡ࢆቑຍࡉࡏࡿࡓ ࡵࠊࢭࣞࣀ࢔ࢭࢱ࣮ࣝ7 ࢆ 5 ᙜ㔞࡟ቑࡸࡋࡓࠋࡑࡢ⤖ᯝ α-MeSe య 8α ࡢ཰⋡ࡣ 48%࡜࡞ࡾ ⱝᖸᨵၿࡉࢀࡓࠋࡇࡢ࡜ࡁβ య 8β ࡶ 43%୚࠼ࡿ⤖ᯝ࡜࡞ࡗࡓࠋβ యࡢ⏕ᡂࡣ CPME ࡢ࢜࢟ ࢯ࢝ࣝ࣋ࢽ࣒࢘࢖࢜ࣥ࡟ᑐࡍࡿ㓄఩ࡀ༑ศ࡛࡞࠿ࡗࡓࡇ࡜࡟ࡼࡿ࡜⪃࠼ࠊ⥆ࡃEntry 3 ࡛ࡣࠊ CPME ࡢ๭ྜࢆቑຍࡉࡏ཯ᛂࢆ⾜ࡗࡓࠋࡑࡢ⤖ᯝࠊα/β ẚࡣ 1.5/1 ࡜࡞ࡾࠊⱝᖸࡢ㑅ᢥᛶྥ

ୖࡀぢࡽࢀࡓࠋࡉࡽ࡟Entry 4 ࡛ࡣ CPME ࡟ẚ࡭ࡼࡾᔞ㧗࠸ TBME ࢆ⏝࠸࡚཯ᛂࢆ⾜ࡗࡓ࡜

ࡇࢁα/β ẚࡣ 3.14/1 ࡟ࡲ࡛ྥୖࡋࡓࠋ᏶඲࡞ α 㑅ᢥᛶࡣᚓࡽࢀ࡞࠿ࡗࡓࡶࡢࡢ඲య࡜ࡋ࡚ࡢ ཰⋡ࡀ 80%ࢆ㉸࠼࡚࠸ࡓࡓࡵࠊ࢔ࣀ࣐࣮␗ᛶయࢆࡑࢀࡒࢀศྲྀࡋ┠ⓗ≀࡬࡜ኚ᥮ࡍࡿࡇ࡜ ࡜ࡋࡓࠋ CH2Cl2⁐፹୰ࠊ࢝ࢳ࢜ࣥᤕᤊ๣࡛࠶ࡿanisole ࢆῧຍ๣࡜ࡋ࡚ຍ࠼ࠊTFA ࢆస⏝ࡉࡏ PMB ᇶࡢ㝖ཤࢆ⾜࡞ࡗࡓ؛⥆࠸࡚ 3఩࠾ࡼࡧ㸲఩Ỉ㓟ᇶࡢ⬺ಖㆤࢆ⤒࡚ࡑࢀࡒࢀⰋዲ࡞཰⋡࡛ 1α ࠾ࡼࡧ1β ࢆᚓࡓ(Scheme 2)ࠋ Scheme 2

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14

➨

➨୕⠇

2-࣓ࢳࣝࢭࣞࣀࣇࢥ࣮ࢫࡢྜᡂ

2-MeSe య 2 ࡢ ๓ 㥑 య ࡜ ࡋ ࡚ ࠊ ྜ ᡂ ࡀ ᐜ ᫆ ࡛ ࠶ ࡿ ࡜ ண ᝿ ࡉ ࢀ ࡿ Methyl

2-bromo-2,6-dideoxy-L-taloside ࢆ㑅ᢥࡋࡓࠋᕷ㈍ࡢ α-Me-L-fucopyranoside 10 ࢆ MeCN ⁐፹୰ࠊ

2,2-DMP ࡜ CSA ࢆ⏝࠸࡚ 3,4-࢖ࢯࣉࣟࣆࣜࢹࣥయ࡛࠶ࡿ໬ྜ≀ 11 ࡬࡜ᐃ㔞ⓗ࡟ኚ᥮ࡋࡓࠋ ⥆࠸࡚ࠊ໬ྜ≀11 ࡟ᑐࡋ CBr4࡜PPh3ࢆస⏝ࡉࡏ⮯⣲໬ࢆヨࡳࡓ28ࠋࡋ࠿ࡋࠊ┠ⓗ࡜ࡍࡿ໬ ྜ≀12 ࡣᚓࡽࢀࡎ↓ᩘࡢ⏕ᡂ≀ࢆ୚࠼ࡿ⤖ᯝ࡜࡞ࡗࡓ(Scheme 3)ࠋ Scheme 3 ⏕ᡂ≀ࡢྠᐃࡣ⾜࠼࡞࠿ࡗࡓࡀࠊ⮯⣲ཎᏊࡢồ᰾ᛶࡀ⁐፹࿴࡟ࡼࡾపୗࡋࠊ ࿴࡞᮲௳ ࡛཯ᛂࡀ㐍⾜ࡋ࡞࠿ࡗࡓ࡜⪃࠼ࠊḟ࡟⮯⣲ཎᏊ࡟ẚ࡭࡚ࡼࡾ࢖༙࢜ࣥᚄࡀ኱ࡁࡃ⁐፹࿴ࢆ ཷࡅ࡟ࡃ࠸ࣚ࢘⣲ཎᏊࢆồ᰾๣࡜ࡋ࡚㑅ᢥࡋࡓࠋ໬ྜ≀ 11 ࢆࢺࣜࣇ࣮ࣛࢺయ 13 ࡬࡜ኚ᥮ ᚋࠊMeCN ⁐፹୰ࠊKI ࡟ࡼࡿࣚ࢘⣲໬ࢆヨࡳࡓࡀ┠ⓗ≀ 14 ࡣᚓࡽࢀ࡞࠿ࡗࡓࠋ Scheme 4 ࡇࢀࡽࡢ⤖ᯝ࠿ࡽࠊ3,4-࢖ࢯࣉࣟࣆࣜࢹࣥᇶ࡟ࡼࡿ⎔ᵓ㐀ࡢᅛᐃ໬ࡢࡓࡵ࡟㑄⛣≧ែࡀ୙ Ᏻᐃ໬ࡉࢀ཯ᛂࡀ㐍⾜ࡋ࡞࠿ࡗࡓ࡜ண᝿ࡋࡓࠋ௦᭰⤒㊰࡜ࡋ࡚ 3,4-࢖ࢯࣉࣟࣆࣜࢹࣥᇶࢆ

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15 Ac ᇶ࡟ኚ᥮ࡋ⎔ᅛᐃࢆゎᾘࡋࡓ⤒㊰ࢆ࡜ࡿࡇ࡜࡜ࡋࡓࠋࡲࡎࠊ໬ྜ≀ 11 ࡢỈ㓟ᇶࢆ PMB ᇶ࡛ಖㆤࡋࡓᚋࠊ80%㓑㓟Ỉ⁐ᾮࢆ⏝࠸࡚ 3,4-ࢲ࢖࣮࢜ࣝయ࡜ࡋࡓࠋ㐟㞳࡜࡞ࡗࡓỈ㓟ᇶࢆ Ac ᇶ࡛ಖㆤࡋࡓᚋࠊCH2Cl2⁐፹୰ࠊTFA ࢆస⏝ࡉࡏ PMB ᇶࢆ㝖ཤࡋ໬ྜ≀ 15 ࢆᚓࡓ (Scheme 5)ࠋḟ࡟ࠊᚓࡽࢀࡓ໬ྜ≀ 15 ࢆ࢔ࢵ࣌ࣝ཯ᛂ࡟౪ࡋࡓࠋࡋ࠿ࡋࠊ┠ⓗ≀࡛࠶ࡿ໬ ྜ≀16 ࡣᚓࡽࢀ࡞࠿ࡗࡓ(Scheme 5)ࠋ Scheme 5 ࡉࡽ࡟ࠊ࢖ࢯࣉࣟࣆࣜࢹࣥయ 11 ࡜ྠᵝࡢ⌮⏤࡛ KI ࢆ⏝࠸࡚ࣚ࢘⣲໬ࢆヨࡳࡀࠊ┠ⓗ≀ 18 ࢆᚓࡿࡇ࡜ࡣ࡛ࡁ࡞࠿ࡗࡓࠋཎᅉ࡜ࡋ࡚⁐፹࿴࡟ࡼࡿồ᰾ᛶࡢపୗࡢ࡯࠿࡟ࡶࠊ4 ఩⨨ ᥮ᇶ࡟ࡼࡿ❧య㞀ᐖࡶ⪃࠼ࡽࢀࡓࡓࡵࠊࣁࣟࢤࣥ࡟ẚ࡭ᔞ㧗ࡃ࡞࠸ள◪㓟࢖࢜ࣥࢆồ᰾๣ ࡜ࡋ࡚㑅ᢥࡋ཯ᛂࢆ⾜ࡗࡓࠋࡋ࠿ࡋࠊTfO య 17 ࡟ᑐࡋ࡚ TBANO2ࢆస⏝ࡉࡏ࡚ࡶ┠ⓗ≀19 ࢆᚓࡿࡇ࡜ࡣ࡛ࡁ࡞࠿ࡗࡓ(Scheme 6)ࠋ Scheme 6 ࡇࢀࡽࡢ⤖ᯝࡼࡾ SN2 ཯ᛂ࡟ࡼࡿ 2 ఩Ⅳ⣲࡬ࡢࣁࣟࢤࣥཎᏊࡢᑟධࡲࡓࡣ࢚ࣆ࣐࣮໬ࡣ ୙ྍ⬟࡛࠶ࡿ࡜ุ᩿ࡋࠊỈ㓟ᇶࡢ㓟໬࡜❧య㑅ᢥⓗ࡞㑏ඖ࡟ࡼࡾ 6-deoxy-L-taloside య࡬࡜

(19)

16 ᑟࡃࡇ࡜࡜ࡋࡓࠋࡲࡎࠊ໬ྜ≀11 ࢆ DMP ࡟ࡼࡾ㓟໬ࡋ໬ྜ≀ 20 ࢆ཰⋡ 85%࡛ᚓࡓࠋḟ࡟ࠊ THF/EtOH ΰྜ⁐፹୰ࠊNaBH4ࢆ⏝࠸࡚㑏ඖࢆ⾜ࡗࡓࠋࡑࡢ⤖ᯝࠊ┠ⓗ࡜ࡍࡿ໬ྜ≀21 ࢆ ཰⋡40㸣࡛ᚓࡓࠋࡇࡢ࡜ࡁࠊ࢚ࣆ࣐࣮࡛࠶ࡿ໬ྜ≀ 11 ࡀ 20%ᚓࡽࢀࡓࠋప㑅ᢥᛶࡢཎᅉ࡜ ࡋ࡚ࠊ࣍࢘⣲ཎᏊୖࡢ㈇㟁Ⲵ࡜1 ఩ OMe ᇶ୰ࡢ㓟⣲ཎᏊୖࡢᏙ❧㟁Ꮚᑐ㛫࡛ࡢ㟼㟁཯Ⓨࡸࠊ 㑏ඖ๣ࡢᔞ㧗ࡉࡀ㛵ಀࡋ࡚࠸ࡿ࡜⪃࠼ࡽࢀࡓࠋࡑࡢࡓࡵEntry 2 ࡛ࡣࠊࣝ࢖ࢫ㓟ᛶࢆ᭷ࡋࠊ ࠿ࡘࠊࡼࡾᔞ㧗࠸㑏ඖ๣࡛࠶ࡿDIBAL-H ࢆ⏝࠸࡚཯ᛂࢆ⾜ࡗࡓࠋࡑࡢ⤖ᯝࠊ໬ྜ≀ 21 ࢆ ཰⋡95%࡛ᚓࡓࠋ(Scheme 7, Table 2)ࠋ Scheme 7 Table 2

⥆࠸࡚ࠊࢺࣜࣇ࣮ࣛࢺయ 22 ࡬࡜ㄏᑟࡋࠊTol2Se 23ࠊpiperidineࠊDIEA ࢆΰྜࡋࡓ DMA

⁐ᾮ࡟ࠊ⁲ୗ࡟࡚ຍ࠼࡚30 ศ㛫᧠ᢾࡋ໬ྜ≀ 24 ࢆᚓࡓ(92%, 2 steps)ࠋḟ࡟ࠊin situ ࢭࣞࣀ

࣮ࣛࢺ࢔ࢽ࢜ࣥἲࢆ⏝࠸࡚Tol ᇶࢆ Me ᇶ࡬࡜ኚ᥮ࡋࡓ21(໬ྜ≀ 25, 64%)ࠋࡑࡢᚋࠊ80%㓑

㓟Ỉ⁐ᾮ୰࡛࢖ࢯࣉࣟࣆࣜࢹࣥᇶࡢ㝖ཤࢆ⾜࠸཰⋡ 83%࡛᭱⤊┠ⓗ≀࡛࠶ࡿ໬ྜ≀ 2 ࢆᚓ

(20)

17

(21)

18

➨

➨ᅄ⠇

3-࣓ࢳࣝࢭࣞࣀࣇࢥ࣮ࢫࡢྜᡂ

ḟ࡟ࠊ3-MeSe-Fuc 3 ࡢྜᡂࢆ⾜ࡗࡓࠋྜᡂࡢ⡆౽ࡉ࠿ࡽ๓㥑య࡜ࡋ࡚ 3-ࣈࣟࣔయࢆ㑅 ᢥࡋࡓࠋ໬ྜ≀10 ࡢ 3,4 ఩ࡢỈ㓟ᇶࢆ Bzld ᇶ࡛ಖㆤࡋࠊࣁࢿࢩ࢔࣭ࣥࣄ࣮ࣗࣛ཯ᛂ29,30_࡟ ࡼࡗ࡚Bzld ᇶࢆ㓟໬ⓗ࡟㛤⿣ࡋ໬ྜ≀ 2723(཰⋡ 47%)࡬࡜ㄏᑟࡋࡓ(Scheme 9)ࠋ Scheme 9 ໬ྜ≀27 ࡜ TolSeK 29 ࢆ 80 °C ࡟࡚཯ᛂࡉࡏࢭࣞࣀ໬ࢆヨࡳࡓࡀฟⓎ≀ࡢᾘ㈝ࡀほࡽࢀ ࡞࠿ࡗࡓࠋࡑࡇ࡛ࠊ཯ᛂ ᗘࢆ100 °C ࡬᪼ ࡋࡓࡀ」㞧࡞ΰྜ≀ࢆᚓࡿ⤖ᯝ࡜࡞ࡗࡓ (Scheme 10)ࠋ Scheme 10 ࡇࡢ⤖ᯝࡣࠊ⮯⣲ཎᏊࡢ⬺㞳⬟ࡀ༑ศ࡛࡞࠿ࡗࡓࡇ࡜࡟ࡼࡿࡶࡢ࡜⪃࠼ࠊࡼࡾ㧗࠸⬺㞳 ⬟ࢆ᭷ࡍࡿࢺࣜࣇ࣮ࣛࢺయࡢྜᡂࢆ⾜ࡗࡓࠋ໬ྜ≀10 ࡟ MeCN ⁐፹୰ࠊTEOFࠊp-TsOH࣭ H2O ࢆస⏝ࡉࡏࠊฟⓎ≀㉁ࡢᾘኻࢆ☜ㄆࡋࡓᚋࠊịᾎ୰࡟࡚ PMBClࠊNaH ࢆຍ࠼㐟㞳ࡢỈ

29 _{Failla, D. L.; Hullar, T. L.; Siskin, S. B. Chem. Commun. 1966, 716.} 30 _{Hanessian, S. Carbohydrate Res. 1966, 2, 86.}

(22)

19

㓟ᇶࢆಖㆤࡋࡓࠋࡑࡢᚋࠊ཯ᛂ⁐ᾮࢆ2M-ሷ㓟࡛ฎ⌮ࡋ 3-OH య 31 ࢆᚓࡓ(཰⋡ 82%)ࠋḟ

࡟ࠊDMP ࢆస⏝ࡉࡏ 3-keto య 32 ࢆ཰⋡ 73%࡛ᚓࡓࠋ⥆࠸࡚ࠊ3-keto య 32 ࢆ MeOH ⁐፹୰ࠊ

0 °C ࡟࡚ NaBH4ࢆ⏝࠸࡚㑏ඖࡋࠊ6-deoxy guloside య 33 ࢆ཰⋡ 82%࡛ᚓࡓࠋࡇࡢ࡜ࡁࠊ༢

୍ࡢࢪ࢔ࢫࢸ࣐࣮ࣞ࢜ࡢࡳࡀᚓࡽࢀࡓࠋguloside య 33 ࢆࢺࣜࣇ࣮ࣛࢺయ 34 ࡬࡜ㄏᑟࡋࠊ TolSeK 29 ࡟ࡼࡿࢭࣞࣥཎᏊࡢᑟධࢆヨࡳࡓࠋࡋ࠿ࡋࠊ┠ⓗ࡜ࡍࡿ໬ྜ≀ 35 ࡣ⑞㊧㔞⛬ᗘ ᚓࡽࢀࡿࡢࡳ࡛࠶ࡗࡓ(Scheme 11)ࠋ Scheme 11 ࡇࡢ࡜ࡁࠊ࢜ࣞࣇ࢕ࣥయ࡜ᛮࢃࢀࡿ๪⏕ᡂ≀ࢆ 80%ᚓࡿ⤖ᯝ࡜࡞ࡗࡓࠋ⨨᥮཯ᛂ࡛ࡣ࡞ ࡃ⬺㞳཯ᛂࡀ㐍⾜ࡋࡓཎᅉ࡜ࡋ࡚ࠊ⬺㞳ᇶ࡜1-OMe ᇶ㛫࠾ࡼࡧồ᰾๣࡜ 4 ఩Ỉ㓟ᇶ㛫࡛ࡢ ❧య཯Ⓨ࠾ࡼࡧ㟼㟁཯Ⓨࡀ⪃࠼ࡽࢀࡿ31ࠋࡋ࠿ࡋࠊ⬺㞳ᇶ㏆ഐࡢ❧య໬Ꮫࡀ㢮ఝࡋ࡚࠸ࡿ໬ ྜ≀25 ࡢྜᡂ࡟ࡣᡂຌࡋ࡚࠸ࡿࠋ2 ఩Ⅳ⣲ཎᏊ࡬ࡢࢭࣞࣥཎᏊᑟධ࡟⏝࠸ࡓ๓㥑య 23 ࡢ ≉ᚩ࡜ࡋ࡚ࠊᑟධ㒊఩࡟㞄᥋ࡍࡿ3,4 ఩Ỉ㓟ᇶࡢ⎔≧࢔ࢭࢱ࣮ࣝಖㆤࡀᣲࡆࡽࢀࡿࠋࡇࢀ࡟ ࡼࡾࠊE2 ⬺㞳ࢆ⾜࠺㝿ࡢ㑄⛣≧ែࡢࡦࡎࡳࡀቑຍࡋ⬺㞳཯ᛂࡀ⇕ຊᏛⓗ࡟୙฼࡜࡞ࡾࠊ⨨ ᥮཯ᛂࡀඃඛࡋ࡚㐍⾜ࡋࡓ࡜ண᝿ࡋࡓ(Fig. 9)ࠋࡲࡓࠊࢺࣜࣇ࣮ࣛࢺయ 13,17 ࡛ࡣ࢚ࣆ࣐࣮໬ ࡀ㐍⾜ࡏࡎࠊࢺࣜࣇ࣮ࣛࢺయ23 ࢆ⏝࠸ࡓࢭࣞࣀ໬ࡀ㐍⾜ࡋࡓ⌮⏤࡜ࡋ࡚ࠊࢭࣞࣥཎᏊࡢཎ Ꮚ༙ᚄࡀ㓟⣲ཎᏊࡢࡑࢀ࡟ẚ࡭࡚኱ࡁࡃࠊ⨨᥮ᇶ(3-H,1-OMe)-ồ᰾✀㛫࡛ࡢ❧య཯Ⓨࡀపῶ

(23)

20 ࡉࢀࡓࡓࡵ࡛࠶ࡿ࡜ண᝿ࡋ࡚࠸ࡿࠋ Fig. 9 ࡲࡓࠊLiakatos ࡽ32ࡣࠊGal 3 ఩࡬ࡢࢳ࢜࢔ࢭࢳࣝᇶࡢᑟධࡢ㝿࡟ࠊ4,6 ఩ࢆ Bn ᇶ࡛ࡣ࡞ࡃ Bzld ᇶ࡛ᯫᶫࡋࡓሙྜ࡟ࡢࡳ┠ⓗ≀ࢆᚓࡿࡇ࡜࡟ᡂຌࡋ࡚࠸ࡿ(Fig. 10)ࠋ Fig. 10

(24)

21

ࡇࢀࡽࡢࡇ࡜࠿ࡽࠊ3-MeSe Fuc 3 ࡢ୰㛫య࡜ࡋ࡚ࠊ1 ఩ࠊ2 ఩Ỉ㓟ᇶࢆ⎔≧ಖㆤࡋࡓ୰㛫

యࡀ᭷ᮃ࡛࠶ࡿ࡜⪃࠼ࡓ(Fig. 11)ࠋ

Fig. 11

L-Fuc 5 ࢆฟⓎ≀㉁࡜ࡋ࡚ Ac ໬ࠊࣈࣟࣔ໬ࡢᚋࠊ1,2-DCE ⁐፹୰ࠊEt₃NࠊMeOH ࢆస⏝ࡉ

ࡏ࢜ࣝࢯ࢚ࢫࢸࣝయ36 ࡬࡜ㄏᑟࡋࡓ(཰⋡ 90%, 3 steps)ࠋAc ᇶࡢ Bn ᇶ࡬ࡢኚ᥮ࡢࡢࡕࠊ㓟 ฎ⌮ࠊ⥆ࡃ⬺࢔ࢭࢳࣝ໬࡟ࡼࡾ1,2-ࢲ࢖࣮࢜ࣝయ 38 ࡬࡜ㄏᑟࡋࡓࠋ⁐፹㔞ࡢ 2,2-DMP ୰ࠊ CSA ࢆస⏝ࡉࡏࠊ1,2 ఩Ỉ㓟ᇶ࡟࢖ࢯࣉࣟࣆࣜࢹࣥᇶࢆᑟධᚋࠊỈ⣲ῧຍ࡟ࡼࡿ Bn ᇶࡢ㝖 ཤࢆ཰⋡ࡼࡃ⾜ࡗࡓࠋ-40 °C ࡛ࡢ 3 ఩㑅ᢥⓗ࡞ࢩࣜࣝಖㆤࡢᚋࠊ㐟㞳࡜࡞ࡗ࡚࠸ࡿ 4 ఩Ỉ㓟 ᇶࢆMOM ᇶ࡛ಖㆤࡋࡓࠋ⥆࠸࡚ 3 ఩Ỉ㓟ᇶࡢ⬺ಖㆤࠊDMP ࡟ࡼࡿ㓟໬ࠊNaBH4࡟ࡼࡿ㑏 ඖࢆ⾜࠸ࠊ⎔≧ಖㆤࢆ᪋ࡋࡓguloside య 45 ࢆᚓࡓ(Scheme 12)ࠋ

(25)

22 Scheme 12 ᚓࡽࢀࡓguloside 45 ࢆࢺࣜࣇ࣮ࣛࢺయ 46 ࡬࡜ㄏᑟᚋࠊTolSeK 29 ࡜཯ᛂࡉࡏࡓ࡜ࡇࢁࠊ ⎔≧ಖㆤࢆ⾜ࡗ࡚࠸࡞࠸35 ࡛ࡣᚓࡽࢀ࡞࠿ࡗࡓࢭࣞࣀయ 47 ࢆ 75%ࡢ཰⋡࡛ᚓࡓࠋTol ᇶࡢ Me ᇶ࡬ࡢኚ᥮ᚋࠊࣇ࢕ࢵࢩ࣮ࣕࢢࣜࢥࢩࢻ໬ࢆ⤒࡚ࠊ┠ⓗ≀࡛࠶ࡿ 3-MeSe-Fuc 3 ࢆ 9%࡜ ࠸࠺ప཰⋡࡞ࡀࡽࡶᚓࡿࡇ࡜࡟ᡂຌࡋࡓ (Scheme 13)ࠋ

(26)

23

(27)

24

➨

5 ⠇ 4-࣓ࢳࣝࢭࣞࣀࣇࢥ࣮ࢫࡢྜᡂ

⥆࠸࡚ࠊ4-MeSe య 4 ࡢྜᡂࢆ⾜࠺ࡇ࡜࡜ࡋࡓࠋ4-bromo-4-deoxyglucoside 2823ࡢ2 ఩Ỉ㓟 ᇶࢆAc ᇶ࡛ಖㆤࡋࡓᚋࠊTolSeK 29 ࢆ⏝࠸࡚ࢭࣞࣀ໬ࢆ⾜࠸ 4-ࢭࣞࣀయ 50 ࢆ 87%ࡢ཰⋡࡛ ᚓࡓࠋḟ࡟ࠊ2-MeSe య 2 ࢆྜᡂࡋࡓ㝿࡜ྠࡌ᮲௳࡛ࠊ໬ྜ≀ 50 ࢆ MeSe య 51 ࡬࡜ኚ᥮ࡋ ࡓ (཰⋡ 53%)ࠋ᭱ᚋ࡟ࠊTHF/MeOH ΰྜ⁐፹୰ࠊNaOMe ࡛ฎ⌮ࡍࡿࡇ࡜࡟ࡼࡾ࢔ࢩࣝ⣔ಖ ㆤᇶࢆ㝖ཤࡋ࡚ࠊ4-MeSe-Fuc 4 ࢆ཰⋡ 96%࡛ᚓࡓ (Scheme 14)ࠋ Scheme 14

(28)

25

➨

➨஧❶ ࢭࣞࣥㄏᑟయࢆ⏝࠸ࡓ

X ⥺ඹ⤖ᬗᵓ㐀ゎᯒ

࠾ࡼࡧ⤖ྜぶ࿴ᛶヨ㦂

➨୍⠇

ࣇࢥ࣮ࢫࣞࢡࢳࣥ AOL ࡢ❧యᵓ㐀ゎᯒ

ᮏ◊✲࡛❧యᵓ㐀ゎᯒ࡟⏝࠸ࡿ⺮ⓑ㉁࡜ࡋ࡚Aspergillus oryzae lectin (AOL)ࢆ㑅ᢥࡋࡓࠋ

AO L ࡣ Ύ 㓇 ࡢ ዃ 㞧 ≀ ࡛ ࠶ ࡿ ࣇ ࢙ ࣜ ࢡ ࣜ ࢩ ࣥ ࡢ 㝖 ཤ ࢆ ┠ ⓗ ࡜ ࡋ ࡚ ༢ 㞳 ࡉ ࢀ

ࡓ 3 1 1 ࢔ ࣑ ࣀ 㓟 ṧ ᇶ ࠿ ࡽ ࡞ ࡿ ศ Ꮚ 㔞 3 4 , 48 1 D a ࡢ ⺮ ⓑ ㉁33_{࡛ ࠶ ࡾ ࠊ ࣄ ࢖ ࣟ ࢳ}

ࣕ ࣡ ࣥ ࢱ ࢣ ࡢ ࣇ ࢥ ࣮ ࢫ ≉ ␗ ⓗ ࣞ ࢡ ࢳ ࣥ (AA L) ࡜ 2 6 %ࡢ ┦ ྠ ᛶ ࢆ ♧ ࡋ ࡚ ࠸

ࡿ ࡇ ࡜ ࡀ ሗ ࿌ ࡉ ࢀ ࡚ ࠸ ࡿ ࡀ ࠊ ࡑ ࡢ ❧ య ᵓ 㐀 ࡣ ሗ ࿌ ࡉ ࢀ ࡚ ࠸ ࡞ ࠸ ࠋ

➨2 ❶࡛ྜᡂࡋࡓ໬ྜ≀ (α-MeSe-Fuc 1α, β-MeSe-Fuc 1β, 2-MeSe-Fuc 2, 3-MeSe-Fuc 3,

4-MeSe-Fuc 4)ࢆ AOL ࡜ࡢඹ⤖ᬗ໬ࠊX ⥺⤖ᬗᵓ㐀ゎᯒ࡬࡜౪ࡋࡓࠋMeSe-Fuc-⺮ⓑ㉁」ྜ

యࡢ❧యᵓ㐀ࡣࣇࢥ࣮ࢫ୰ࡢࢭࣞࣥཎᏊࢆ⏝࠸ࡓSAD ἲࡲࡓࡣ MAD ἲ࡟ࡼࡿ఩┦Ỵᐃ࡟

ࡼࡾゎᯒࡉࢀࡓࠋᚓࡽࢀࡓࣜ࣎ࣥࣔࢹࣝࢆFig. 12 ࡟♧ࡍࠋAOL ࡢ඲యᵓ㐀ࡣࠊ6 ᅇᢡࡾࡓ

ࡓࡲࢀࡓβ ࣉࣟ࣌ࣛ࡟ࡼࡾᵓᡂࡉࢀ࡚࠾ࡾࠊྠࡌࣇࢥ࣮ࢫㄆ㆑ࣞࢡࢳ࡛ࣥ࠶ࡿ AAL34ࡸAFL8

࡜㢮ఝࡋࡓᵓ㐀࡛࠶ࡗࡓࠋࡲࡓࠊㄏᑟయࡢ㐪࠸࡟ࡼࡿ❧యᵓ㐀࡬ࡢᙳ㡪ࡣぢࡽࢀ࡞࠿ࡗࡓࠋ

Fig. 12 Determined structure of AOL complexed with a) α-MeSe-Fuc 1α, b) β-MeSe-Fuc 1β and

c) 2-MeSe-Fuc 2

33_{Ishida, H.; Moritani, T.; Hata, Y.; Kawato, A.; Suginami, K.; Abe, Y.; Imayasu, S. Biosci.}

Biotechnol. Biochem. 2002, 66, 1002.

34_{Fujihashi, M.; Peapus, D. H.; Kamiya, N.; Nagata, Y.; Miki, K. Biochemistry 2003, 42, 11093.}

(29)

26

ࡋ࠿ࡋࠊα-MeSe-Fuc 1α ࢆ⏝࠸ࡓሙྜ࡛ࡣࠊSite 4 ࡟࠾࠸࡚ㄏᑟయࡢ௦ࢃࡾ࡟ HEPES ࡢ⤖ྜ

ࡀほᐹࡉࢀࡓࠋ ࣇࢥ࣮ࢫ⤖ྜ㒊఩ࡣࣉࣟ࣌ࣛࢆᵓᡂࡍࡿβ ࣈ࣮ࣞࢻࡢ㛫㝽࡟ᏑᅾࡋࠊFuc ࡢ⎔ෆ㓟⣲ࠊ2 ఩ࠊ3 ఩ࠊ4 ఩Ỉ㓟ᇶ࡜ࡢ㛫࡛Ỉ⣲⤖ྜࢆᙧᡂࡋ࡚࠸ࡿࡇ࡜ࡀ᫂ࡽ࠿࡜࡞ࡗࡓࠋࡲࡓࠊ⤖ྜ 㒊఩࡟ࡼࡾࣇࢥ࣮ࢫ࡜ࡢỈ⣲⤖ྜ࡟ᐤ୚ࡍࡿ࢔࣑ࣀ㓟ࡢ✀㢮ࡸᩘ࡟┦㐪ࡀぢࡽࢀࡓ(Fig. 13)ࠋࡇࡢࡇ࡜ࡣࠊ⤖ྜ㒊఩㛫࡟࠾࠸࡚ᇶ㉁ぶ࿴ᛶ࡟ᕪࡀ࠶ࡿࡇ࡜ࢆ♧၀ࡍࡿ⤖ᯝ࡛࠶ࡿࡀࠊ ࡇࢀ௨ୖࡢ㏣ཬࡣ⾜ࢃ࡞࠿ࡗࡓࠋFuc ㄏᑟయ 3,4 ࡟࠾࠸࡚ඹ⤖ᬗࡀᚓࡽࢀ࡞࠿ࡗࡓཎᅉ࡜ࡋ ࡚ࠊ┦஫స⏝࡟㛵୚ࡍࡿỈ㓟ᇶࢆ࣓ࢳࣝࢭࣞࣀᇶ࡛⨨᥮ࡋࡓࡇ࡜࡟ࡼࡾAOL ࡜ࡢỈ⣲⤖ྜ ᙧᡂࡀ㜼ᐖࡉࢀࡓࡓࡵ࡜ண᝿ࡋ࡚࠸ࡿࠋࡋ࠿ࡋࠊ᭱㐺࡞⤖ᬗ໬᮲௳ࡀぢࡘ࠿ࡽ࡞࠿ࡗࡓࡔ ࡅࡢྍ⬟ᛶࡶ࠶ࡿࠋ Fig. 13

(30)

27

➨

➨஧⠇

AOL ࡜ࡢぶ࿴ᛶヨ㦂

⤖ᬗ໬ࡢᡂྰࡀ㓝⣲-ᇶ㉁㛫┦஫స⏝ࡢ⛬ᗘࡢᣦᶆ࡜ࡣ࡞ࡽ࡞࠸ࡓࡵࠊAOL ࡜ࡢぶ࿴ᛶࢆ ⾲㠃ࣉࣛࢬࣔࣥඹ㬆(SPR)ἲ࡟ࡼࡾ ᐃࡍࡿࡇ࡜࡜ࡋࡓࠋ࢔࣑ࣀ࢝ࢵࣉࣜࣥࢢ࡟ࡼࡾ AOL ࢆࢭࣥࢧ࣮ࢳࢵࣉ(CM5)࡬࡜ᅛᐃ໬ࡋࠊྛ⃰ᗘ࡟ᕼ㔘ࡋࡓࢭࣞࣀ໬ࣇࢥ࣮ࢫࢆὶࡋ ᐃࢆ⾜ ࡗࡓࠋ ᐃࡢ⤖ᯝࢆTable 3 ࡟♧ࡍࠋ

㻌

K

d ඹ⤖ᬗ໬䛾ᡂྰ

α-Me-Fuc (11)

71±8.6

-

α-MeSe-Fuc (1α)

85±18

䚽

β-MeSe-Fuc (1β)

121±18

䚽

2-MeSe-Fuc (2)

52±2.5

䚽

3-MeSe-Fuc (3)

501±269

㽢

4-MeSe-Fuc (4)

624±108

㽢 Table 3 ⯆࿡῝࠸ࡇ࡜࡟࢔ࣀ࣐࣮఩ࡢ❧య໬Ꮫࡣぶ࿴ᛶ࡟ᑐࡋ࡚࠶ࡲࡾᙳ㡪ࢆ୚࠼࡚࠸࡞࠿ࡗࡓࠋ ࡑࡋ࡚ࠊ⺮ⓑ㉁࡜ࡢඹ⤖ᬗ໬࡟ኻᩋࡋࡓㄏᑟయ(3,4)࡜ AOL ࡜ࡢぶ࿴ᛶࡣࠊᡂຌࡋࡓࡶࡢ (1

α

,1

β

,2)࡟ẚ࡭ 4 ಸ௨ୖప࠸್࡜࡞ࡾࠊ⤖ᬗᵓ㐀ゎᯒࡢ⤖ᯝ࠿ࡽண᝿ࡉࢀ࡚࠸ࡓࡼ࠺࡟ࠊࣇ ࢥ࣮ࢫࡢ3 ఩ࡲࡓࡣ 4 ఩࡛ࡢ⨨᥮ࡀ⺮ⓑ㉁࡜ࡢ┦஫స⏝࡟ᙳ㡪ࢆ୚࠼࡚࠸ࡿࡇ࡜ࢆ♧ࡍ⤖ ᯝ࡜࡞ࡗࡓࠋࡲࡓࠊពእ࡞஦࡟2-MeSe-Fuc 2 ࡀ᭱ࡶ㧗࠸ぶ࿴ᛶࢆ♧ࡋࡓࠋࡇࡢ⌧㇟࡟ᑐࡍ ࡿ⪃ᐹࢆ௨ୗ࡟㏙࡭ࡿࠋFig. 14 ࡟♧ࡍࡼ࠺࡟ࠊ2 ఩࡟఩⨨ࡍࡿࢭࣞࣥཎᏊ࡜ 3 ఩Ỉ㓟ᇶ࡜ࡢ 㛫࡛Ỉ⣲⤖ྜࢆᙧᡂࡋ 3 ఩㓟⣲ཎᏊࡢồ᰾ᛶࡀ㧗ࡲࡗࡓ⤖ᯝࠊ⺮ⓑ㉁࡜ࡢ⤖ྜࡀᙉࡃ࡞ࡗ ࡓ࡜ண᝿ࡋࡓࠋ

(31)

28

(32)

29

➨

➨୍㒊

ࡲ࡜ࡵ

➨୍㒊࡛ࡣࠊࡇࢀࡲ࡛ሗ࿌ࡢ࡞࠿ࡗࡓࢭࣞࣀ໬⢾ࡢ⣔⤫ⓗྜᡂࢆࣇࢥ࣮ࢫ࡟ᑐࡋ࡚⾜ࡗ ࡓࠋࡉࡽ࡟ࠊྜᡂࡋࡓ໬ྜ≀ࢆ⏝࠸࡚⺮ⓑ㉁࡜ࡢඹ⤖ᬗᵓ㐀ゎᯒ࠾ࡼࡧぶ࿴ᛶ ᐃࢆ⾜ࡗ ࡓࠋࢭࣞࣥཎᏊࡢ࢔ࣀ࣐࣮఩࡬ࡢᑟධ࡛ࡣࠊΰྜࢭࣞࣀ࢔ࢭࢱ࣮ࣝࢆ࢜࢟ࢯ࢝ࣝ࣋ࢽ࣒࢘ ࢖࢜ࣥ࡟స⏝ࡉࡏࡿࡇ࡜࡟ࡼࡾඹ㏻ࡢ୰㛫య࠿ࡽ࢔ࣀ࣐࣮␗ᛶయࢆࡑࢀࡒࢀྜᡂࡋࡓࠋᙜ ึࠊ2 ఩࠾ࡼࡧ 3 ఩࡬ࡢ SN2 ཯ᛂࢆ⤒⏤ࡋࡓࢭࣞࣀཎᏊᑟධ࡟ၥ㢟ࡀ࠶ࡗࡓࡀࠊᑟධ㒊఩࡟ 㞄᥋ࡍࡿࢩࢫࢲ࢖࣮࢜ࣝ࡬⎔≧ಖㆤᇶࢆᑟධࡍࡿࡇ࡜࡟ࡼࡾࢭࣞࣀ໬ࢆ཰⋡ࡼࡃ⾜ࡗࡓࠋ ᚓࡽࢀࡓㄏᑟయࢆ❧యᵓ㐀ࡀᮍゎ࡛᫂࠶ࡗࡓࣇࢥ࣮ࢫㄆ㆑⺮ⓑ㉁AOL ࡢᵓ㐀ゎᯒ࡬⏝࠸ࡓ ⤖ᯝࠊࡑࡢ❧యᵓ㐀ࢆึࡵ࡚᫂ࡽ࠿࡜ࡍࡿࡇ࡜ࡀ࡛ࡁࡓࠋࡲࡓࠊぶ࿴ᛶ ᐃࢆ⾜࠸ㄏᑟయ 㛫࡛ࡢ┦㐪ࢆぢฟࡍࡇ࡜ࡀ࡛ࡁࡓࠋ௨ୖࡢ⤖ᯝ࠿ࡽࠊᇶ㉁ㄆ㆑ᶵᵓࡀᮍゎ᫂࡞⺮ⓑ㉁ࡢඹ ⤖ᬗᵓ㐀ゎᯒ࡟࠾ࡅࡿࢭࣞࣀ໬⢾⩌ࡢ฼⏝ࡢ᭷⏝ᛶ࡜ࠊඹ⤖ᬗ໬࡟ྥࡅࡓࢭࣞࣀ໬⢾᥈⣴ ࡛ࡢSPR ᐃࡢᐇ⾜ྍ⬟ᛶࡀ♧ࡉࢀࡓࠋ

(33)

30

➨

➨஧㒊

⢾⺮ⓑ㉁ࡢ X ⥺⤖ᬗᵓ㐀ゎᯒࡢ㎿㏿໬ࢆᣦྥࡋࡓࢭࣞࣀ໬⢾ࡢ㛤Ⓨ

➨୍❶◊✲⫼ᬒ

➨୍㒊࡛ࡣࠊ⢾ㄆ㆑⺮ⓑ㉁࡛࠶ࡿࣞࢡࢳࣥࢆᑐ㇟࡜ࡋࡓ X ⥺⤖ᬗᵓ㐀ゎᯒ࡬ࡢࢭࣞࣀ໬ ⢾฼⏝ࡢᣑ඘࡟ྥࡅࡓከᵝ࡞ᶆ㆑ᵝᘧࢆ᭷ࡍࡿࢭࣞࣀ໬⢾ࡢྜᡂ࠾ࡼࡧࡑࢀࡽࢆ⏝࠸ࡓ❧ యᵓ㐀ゎᯒࡢ⤖ᯝࢆሗ࿌ࡋࡓࠋ➨஧㒊࡛ࡣࠊ⢾㙐ࢆࣜ࢞ࣥࢻ࡜ࡋ࡞࠸⺮ⓑ㉁ࠊࡇࡇ࡛ࡣ N ⤖ྜᆺ⢾⺮ⓑ㉁ࡢ❧యᵓ㐀ゎᯒࡢ㎿㏿໬࡟ྥࡅࡓࣉ࣮ࣟࣈྜᡂ࡜ࡑࡢᛂ⏝࡟ࡘ࠸࡚ሗ࿌ࡍ ࡿࠋ ⺮ⓑ㉁ࡣ⩻ヂᚋࠊࣜࣥ㓟໬35ࡸ࢔ࢭࢳࣝ໬36࡞࡝ࡢಟ㣭ࢆཷࡅࡿࡇ࡜࡟ࡼࡾࠊάᛶࡢㄪ〇 ࡸࠊ⺮ⓑ㉁ศゎ㓝⣲࡬ࡢ⪏ᛶ➼ࢆㄪ⠇ࡋ࡚࠸ࡿࠋࡇࡢࡼ࠺࡞⩻ヂᚋಟ㣭ࡢ୍ࡘ࡟⢾㙐ಟ㣭 ࡀᣲࡆࡽࢀࠊ┿᰾⣽⬊࡟⏤᮶ࡍࡿ⺮ⓑ㉁ࡢ⣙ 50㸣௨ୖࡣ࡞ࢇࡽ࠿ࡢ⢾㙐ಟ㣭ࢆཷࡅ࡚࠸ࡿ ࡜ሗ࿌ࡉࢀ࡚࠸ࡿ37ࠋ⢾⺮ⓑ㉁࡟⤖ྜࡋࡓ⢾㙐ࡢ≉ᚩ࡜ࡋ࡚ࠊྠ୍ࡢ⺮ⓑ㉁࡛ࡶ⏤᮶࡜࡞ࡿ ⣽⬊ࡸࡑࡢ⣽⬊ࡢ≧ែ➼࡟ࡼࡾ⢾㙐ᵓ㐀࡟┦㐪ࡀぢࡽࢀࡿࡇ࡜ࡀ▱ࡽࢀ࡚࠾ࡾࠊࡇࡢࡼ࠺ ࡞≉ᚩࡣᚤᑠ୙ᆒ୍ᛶ࡜࿧ࡤࢀ࡚࠸ࡿࠋࡲࡓࠊ⺮ⓑ㉁⾲㠃࡟Ꮡᅾࡍࡿ⢾㙐ࡣ㧗࠸⮬⏤ᗘࢆ ᭷ࡋ࡚࠾ࡾศᏊ୰ࡢ୍ᐃࡢ఩⨨࡟Ꮡᅾࡍࡿࢃࡅ࡛ࡣ࡞࠸38ࠋࡇࡢࡼ࠺࡞⢾㙐ࡢ≉ᚩࡣࠊᆒ୍ ࡞ศᏊࡀ✵㛫ⓗ࡟つ๎ṇࡋࡃ㓄ิࡍࡿࡇ࡜ࢆᚲせ࡜ࡍࡿ⤖ᬗ໬ࡢ㜼ᐖせᅉ࡜࡞ࡗ࡚࠸ࡿࠋ ࡇࡢၥ㢟࡟ᑐࡋࠊᚑ᮶࡛ࡣࠊ⢾㙐ಟ㣭ࢆ⾜ࢃ࡞࠸ཎ᰾⏕≀ࢆ⏝࠸ࡓヨᩱㄪ〇ࡸ⢾ຍỈศ ゎ㓝⣲࡟ࡼࡿ⢾㙐㝖ཤ࡟ࡼࡾ⢾㙐㒊ศࢆྵࡲ࡞࠸⺮ⓑ㉁ࢆㄪ〇ࡋ⤖ᬗ໬࡟౪ࡋ࡚࠸ࡿࠋࡋ ࠿ࡋࠊ⺮ⓑ㉁ࡢ⁐ゎᛶ࡞࡝࡟ᐤ୚ࡍࡿ⢾㙐ࡢ㝖ཤࡣ⁐ゎᛶࡢపୗࡦ࠸࡚ࡣ⺮ⓑ㉁ࡢจ㞟ࢆ ᘬࡁ㉳ࡇࡋࠊ⤖ᬗ໬ࡀ୙ྍ⬟࡜࡞ࡿሙྜࡀ࠶ࡿࠋࡑࡇ࡛ࠊᮏ◊✲࡛ࡣ୙ᆒ୍࡞⢾㙐ࢆᆒ୍ ࠿ࡘࢭࣞࣥᶆ㆑ࡋࡓ⢾㙐࡬࡜ᤄࡆ᭰࠼ࡿࡇ࡜࡟ࡼࡾୖ㏙ࡋࡓၥ㢟ࢆゎỴࡉࡽ࡟⺮ⓑ㉁ࡢ㔜 ཎᏊᶆ㆑ࢆྠ᫬࡟⾜࠸ࠊ⢾⺮ⓑ㉁ࡢ X ⥺⤖ᬗᵓ㐀ゎᯒࡢ㎿㏿໬ࡀྍ⬟࡜࡞ࡿ࡜⪃࠼◊✲ࢆ

35_{Humphrey, S. J.; James, D. E.; Mann, M. Trends Endocrinol. Metabol. 2015, 26, 676.} 36_{Allfrey, V. G.; Faulkner, R.; Mirsky, A. E. Proc. Natl Acad. Sci. USA, 1964, 51, 786.} 37_{Apweiler, R.; Hermjakob, H.; Sharon, N. Biochim. Biophys. Acta 1999, 1473, 4.}

38_{Yamaguchi, T.; Sakae, Y.; Zhang, Y.; Yamamoto, S.; Okamoto, Y.; Kato, K. Angew. Chem. Int.}

(34)

31 㛤ጞࡋࡓ(Fig. 15)ࠋ Fig. 15 ⢾ຍỈศゎ㓝⣲ ࢭࣞࣀ໬⢾ ⢾㌿⛣㓝⣲

(35)

32

⺮ ⓑ ㉁ ࡬ ࡢ ࢭ ࣞ ࣀ ໬ ⢾ ࡢ ᑟ ධ ࡟ ࡣ ࠊ ᒣ ᮏ ࡽ ࡟ ࡼ ࡾ ⢾ ㌿ ⛣ ά ᛶ ࡀ ሗ ࿌ ࡉ ࢀ ࡚ ࠸ ࡿ

Endo-β-N-acetylglucosaminidase (ENGase, Endo M) (EC 3.2.1.96)39,40_{ࢆ⏝࠸ࡿࡇ࡜࡜ࡋࡓࠋ}

Endo-M ࡣ⣒≧⳦ Mucor hiemalis ࠿ࡽ༢㞳ࡉࢀࡓ࢚ࣥࢻࢢࣜࢥࢩࢲ̿ࢮࡢ୍✀࡛ N ⤖ྜᆺ⢾ 㙐୰ࡢ࢟ࢺࣅ࣮࢜ࢫ⤖ྜ(GlcNAcβ(1-4)GlcNAc)ࢆ GlcNAc ୍ṧᇶ⺮ⓑ㉁ഃ࡟ṧࡍࡼ࠺࡟ຍỈ ศゎࡍࡿࠋࡇࡢ㝿࡟ࠊGlcNAc ࢆ᭷ࡍࡿ㐺ᙜ࡞⢾ཷᐜయࡀ࠶ࢀࡤ㐟㞳ࡋࡓ⢾㙐ࢆࡑࡢཷᐜయ ࡟㌿⛣ࡍࡿ࡜࠸࠺ᛶ㉁ࢆᣢࡘ(Fig. 16)ࠋࡇࡢࡼ࠺࡞⢾㌿⛣ᵝάᛶࢆ᭷ࡍࡿ Endo-M ࢆ⏝࠸ࡿ ࡇ࡜࡟ࡼࡾຠ⋡ⓗ࡞⺮ⓑ㉁࡬ࡢࢭࣞࣀ໬⢾ࡢᑟධࡀྍ⬟࡛࠶ࡿ࡜⪃࠼ࡓࠋ Fig. 16

39_{Kadowaki, S.; Yamamoto, K.; Fujisaki, M.; Izumi, K.; Tochikura, T.; Yokoyama, T.; Agric. Biol.}

Chem. 1990, 54, 97.

40_{Yamamoto, K.; Kadowaki, S.; Watanabe, J.; Kumagai, H.; Biochem. Biophys. Res. Commun.}

(36)

33

➨

➨஧❶ ศᏊタィ

ᒣཱྀࡽ41ࡣࠊN ⤖ྜᆺ⢾㙐(High mannose ᆺ)ࢆᵓᡂࡍࡿྛ⢾ṧᇶࡢ⁐ᾮ୰࡛ࡢ⮬⏤ᗘ ࢆNMR ࡟ࡼࡾホ౯ࡋ࡚࠸ࡿࠋࡇࢀ࡟ࡼࡿ࡜ࠊ4 ṧᇶ௨ୖ࡟࠾࠸࡚⢾㒊ศࡢ⮬⏤ᗘࡀⴭ ࡋࡃቑຍࡋ࡚࠸ࡿࠋ఩┦Ỵᐃࢆ⾜࠺ࡓࡵ࡟ࡣࠊ┠༳࡜࡞ࡿࢭࣞࣥཎᏊࡀ୍ᐃࡢ఩⨨࡟Ꮡ ᅾࡋ࡚࠸ࡿࡇ࡜ࡀᚲせ࡛࠶ࡿࡓࡵࠊᮏ◊✲࡛⏝࠸ࡿ໬ྜ≀࡜ࡋ࡚ࡣࠊ3 ⢾௨ෆࡢ໬ྜ≀ ࡀ᭷⏝࡛࠶ࡿ࡜⪃࠼ࡽࢀࡿࠋࡲࡓࠊࢭࣞࣥཎᏊᑟධ఩⨨࡜ࡋ࡚ࡣࠊ⢾㌿⛣㓝⣲࡟ࡼࡿᇶ ㉁ㄆ㆑࡟㛵୚ࡋ࡞࠸GlcN ṧᇶࡢ 3 ఩࠾ࡼࡧ 4 ఩࠶ࡿ࠸ࡣ࣐ࣥࣀ࣮ࢫṧᇶ୰ࡢ 1ࠊ3ࠊ4ࠊ 6 ఩ࡢ࠸ࡎࢀ࠿ࡀ᭷ຠ࡛࠶ࡿ࡜ண᝿ࡉࢀࡿࠋࡉࡽ࡟ࠊྜᡂࡢ⡆౽ࡉࢆຍ࿡ࡋ࣐ࣥࣀ࣮ࢫ 1 ఩࡟ࢭࣞࣥཎᏊࢆ᭷ࡍࡿ஧⢾ Se-Man β(1-4) GlcNAc ࢆᇶᮏ㦵᱁࡜ࡋࡓࠋࡲࡓࠊ⢾࢜࢟ ࢧࢰࣜࣥయࡀEndo-M ࡢᇶ㉁࡜ࡋ࡚᭷⏝࡛࠶ࡿࡇ࡜ࡀሗ࿌ࡉࢀ࡚࠸ࡿࡇ࡜࠿ࡽ42ࠊᮏ◊

✲࡟࠾ࡅࡿ┠ⓗ≀࡜ࡋ࡚Se-Man β(1-4) GlcNAc-oxazoline ࢆタᐃࡋࡓ(Fig 17)ࠋ

Fig. 17

41_{Yamaguchi, T.; Sakae, Y.; Zhang, Y.; Yamamoto, S.; Okamoto, Y.; Kato, K. Angew. Chem. Int.}

Ed. 2014, 53, 10941.

42_{Fujita, M.; Shoda, S.; Haneda, K.; Inazu, T.; Takegawa, K.; Yamamoto, K. Biochim Biophys Acta}

(37)

34

➨

➨୕❶ ᶆ㆑ศᏊࡢྜᡂ

Man 㒊ศࡢ GlcN 㒊ศ࡬ࡢ SN2 ཯ᛂ࡟ࡼࡾ Se-Man β(1-4) GlcNAc-oxa 㦵᱁ࡢᵓ⠏ࢆ⾜࠺ࡓ

ࡵࠊGlcNAc 㒊ศࡢ๓㥑య࡜ࡋ࡚ࠊGlcN ࡢ C4 ࢚ࣆ࣐࣮࡛࠶ࡿ GalN ࢆ㑅ᢥࡋࡓࠋ࢞ࣛࢡࢺ ࢧ࣑ࣥሷ㓟ሷ52 ࡢ࢔ࢭࢳࣝ໬ࠊ3-(dimethylamino)-1-propylamine ࡟ࡼࡿ୍఩࢔ࢭࢳࣝᇶࡢ㑅 ᢥⓗ㝖ཤ43ࢆ⾜ࡗࡓᚋࠊ୍఩Ỉ㓟ᇶ࡬TBDPS ᇶࢆᑟධࡋࡓࠋࢺ࣮ࣜ࢜ࣝయ 54 ࡬ࡢኚ᥮ࡢᚋ (཰⋡ 86%)ࠊ3 ఩࠾ࡼࡧ 6 ఩Ỉ㓟ᇶ࡬ࡢ఩⨨㑅ᢥⓗ࡞࢔ࢭࢳࣝ໬44࡬࡜౪ࡋㄏᑟయ55 (཰⋡ 66%)ࢆᚓࡓ (Scheme 15)ࠋ Scheme 15

43_{Andersen, S. M.; Heuckendorff, M.; Jensen, H. H. Org. Lett. 2015, 17, 944.} 44_{Ren, B.; Rahm, M.; Zhang, X.; Zhou, Y.; Dong, H. J. Org. Chem. 2014, 79, 8134.}

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35 Man 㒊ศࡢྜᡂ࡛ࡣ࣐ࣥࣀࢩࣝࣈ࣑ࣟࢻ 56 ࡟ TolSeK 29 ࢆస⏝ࡉࡏࢭࣞࣀ࣐ࣥࣀࢩࢻ 57 ࢆ཰⋡45%࡛ᚓࡓ(Scheme 16)ࠋ Scheme 16 ḟ࡟ࠊ஧⢾㦵᱁ࡢᵓ⠏ࢆ⾜ࡗࡓࠋἙྜࡽ21࡟ࡼࡾሗ࿌ࡉࢀ࡚࠸ࡿin situ ࡛ࡢࢭࣞࣀ࢔ࢽ ࢜ࣥⓎ⏕ἲ࡟๎ࡾࠊ⬺ẼࡋࡓDMF ୰࡟࡚ Cs2CO3Ꮡᅾୗࠊࢭࣞࣀ࣐ࣥࣀࢩࢻ57 ࡟ᑐࡋ Me2NH ࢆస⏝ࡉࡏࢭࣞࣀ࢚ࢫࢸࣝࡢάᛶ໬ࢆ⾜ࡗࡓࠋࡑࡋ࡚ࠊู㏵ㄪ〇ࡋࡓGalN ࡢࢺࣜࣇ࣮ࣛࢺ ㄏᑟయࢆస⏝ࡉࡏࠊ஧⢾㦵᱁ࡢᵓ⠏ࢆ 63 %ࡢ཰⋡࡛⾜ࡗࡓࠋᚓࡽࢀࡓ໬ྜ≀ 58 ࡢ 1JCH coupling ࢆ ᐃࡋࡓ࡜ࡇࢁ 157.5 Hz ࡜࡞ࡗࡓࠋࡇࢀࡣ Yu ࡽ࡟ࡼࡾሗ࿌ࡉࢀ࡚࠸ࡿ β ࣐ࣥࣀ ࢩࢻ࡟ࡳࡽࢀࡿ≉ᚩⓗ࡞್45(160.5 Hz)࡟㏆ࡃࠊα ࣐ࣥࣀࢩࢻࡢ್(173.2 Hz)࡜ࡣ኱ࡁࡃ␗࡞ ࡗ࡚࠸ࡓࠋࡇࡢࡇ࡜࠿ࡽࠊ໬ྜ≀58 ࡣ β ࢔ࣀ࣐࣮࡛࠶ࡿ࡜⤖ㄽ௜ࡅࡓࠋḟ࡟ᚓࡽࢀࡓ஧⢾ 58 ࢆ࣑࣊࢔ࢭࢱ࣮ࣝ࡬࡜ 59 ࡜ኚ᥮ᚋࠊ࢜࢟ࢧࢰࣜࣥయ 60 ࡬࡜ㄏᑟࡋࡓࠋึࡵ✀ࠎࡢㄽᩥ ࡛ሗ࿌ࡉࢀ࡚࠸ࡿࡼ࠺࡟H2O ୰࡛ࡢ࢜࢟ࢧࢰࣜࣥ໬ࢆヨࡳࡓ࡜ࡇࢁཎᩱࡢจ㞟ࡀほᐹࡉࢀ ࡓࠋࡑࡢࡓࡵࠊ཯ᛂ⁐፹࡜ࡋ࡚THF/H2O ࡢΰྜ⁐፹ࢆ⏝࠸ࡓࠋ࣑࣊࢔ࢭࢱ࣮ࣝయ 59 ࡟ DMCࠊ Et3N ࢆస⏝ࡉࡏࡓ࡜ࡇࢁ㛤ጞ 10 ศ⛬ᗘ࡛཯ᛂࡢ཰᮰ࡀ TLC ୖ࡟࡚☜ㄆࡉࢀࡓࠋࡋ࠿ࡋࠊ ⃰⦰ᚋࢩࣜ࢝ࢤ࣒ࣝ࢝ࣛࢡ࣐ࣟࢺࢢࣛࣇ࢕࣮࡟ࡼࡿ⢭〇ࢆ⾜ࡗࡓ⤖ᯝࠊ࣑࣊࢔ࢭࢱ࣮ࣝయ 59 ࡲࡓࡣ࣓ࢳࣝࢢࣜࢥࢩࢻࡢࡳࡀᚓࡽࢀ┠ⓗ≀ࡢᾘኻࡀほᐹࡉࢀࡓࠋᏳᐃ࡛࠶ࡿ࡜୍⯡ⓗ ࡟▱ࡽࢀ࡚࠸ࡿ࢜࢟ࢧࢰࣜࣥయࡀࢩࣜ࢝ࢤࣝ୰࡛ศゎࡋࡓࡇ࡜ࢆ♧၀ࡍࡿ⤖ᯝࢆཷࡅ࡚ࠊ ᚋฎ⌮ࡢ㝿࡟㣬࿴Ⅳ㓟Ỉ⣲ࢼࢺ࣒ࣜ࢘Ỉ⁐ᾮ࡟ࡼࡿὙίࢆ⾜࠸ࠊ࢔࣑ࣀࢩࣜ࢝ࢤࣝ࡟ࡼࡿ

45_{Yu, B.; van Ingen, H.; Vivekanandan, S.; Rademacher, C.; Norris, S. E,; Freedberg, D. I. J. Magn.}

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36

⢭〇ࢆ⾜ࡗࡓ࡜ࡇࢁࠊ95%࡜࠸࠺Ⰻዲ࡞཰⋡࡛࢜࢟ࢧࢰࣜࣥయ 60 ࢆᚓࡿࡇ࡜࡟ᡂຌࡋࡓࠋ

᭱ᚋ࡟ᚓࡽࢀࡓ໬ྜ≀60 ࢆ⬺ಖㆤ࡬࡜౪ࡍࡿࡇ࡜࡛ࠊ┠ⓗ≀ 61 ࡢྜᡂࢆ㐩ᡂࡋࡓ(Scheme

17)ࠋ

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37

➨

➨ᅄ❶

Endoglycosidase ࢆ⏝࠸ࡓ⢾㌿⛣཯ᛂࡢ᳨ウ

⥆࠸࡚ྜᡂࡋࡓ໬ྜ≀61 ࢆ⢾౪୚యࠊGlcNAc-pNP 62 ࢆ⢾ཷᐜయ࡜ࡋ࡚⏝࠸࡚ࠊEndo M ࡟ࡼࡿࢢࣜࢥࢩࣝ໬ࡢ᳨ウࢆ⾜ࡗࡓ (Scheme 18, Table 4)ࠋ Scheme 18 Table 4

Entry 1 ࡛ࡣࠊO-Man β (1-4)GlcNAc oxa ࢆ⏝࠸࡚⢾㌿⛣ࢆ⾜ࡗ࡚࠸ࡓㄽᩥ41ࢆཧ⪃࡟ࠊ⢾

౪୚య࡜ཷᐜయࡢẚࡀ3:1 ࡜࡞ࡿࡼ࠺࡟ㄪᩚࡋ཯ᛂ࡬౪ࡋࡓࠋࡑࡢ⤖ᯝࠊ⢾౪୚యࡢῶᑡ࡜

㌿⛣⏕ᡂ≀࡜ᛮࢃࢀࡿࢩࢢࢼࣝࡢቑຍࡀHPLC ࡟࡚ほ ࡉࢀࡓ(Fig. 18)ࠋ㉁㔞ศᯒࡢ⤖ᯝࠊ

ಖᣢ᫬㛫ࡀ21 ศࡢࣆ࣮ࢡ࡟┠ⓗ≀ࡀྵࡲࢀ࡚࠸ࡿࡇ࡜ࡀ᫂ࡽ࠿࡜࡞ࡗࡓ(Fig. 19)ࠋࡲࡓࠊ

ࡇࡢ࡜ࡁ┠ⓗ≀࡜ᛮࢃࢀࡿศᏊ࢖࢜ࣥࣆ࣮ࢡࡣࢭࣞࣥཎᏊࢆ᭷ࡍࡿ໬ྜ≀࡟≉ᚩⓗ࡟ࡳࡽ ࢀࡿྠ఩యࣆ࣮ࢡࢆ♧ࡋࡓࠋ

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38

Fig. 18 RP-HPLC analysis of transglycosylation reaction.

Reaction time: A. 0.5 h, B. 2.0 h, C. 14 h.

Column: Inertsil ODS-3 (125×2.1 mm), Detection: UV detector (260 nm) Eluent A:0.1% TFA aq., Eluent B: MeCN containing 0.1% TFA

Eluent (Binary gradient 14% of eluent B, 1 mL/min) was employed.

Fig. 19 ESI-TOF MS of glycosylated compound

ࡉࡽ࡟ࠊ1H-NMR ࡼࡾ࣐ࣥࣀࢩࣝࢢࣝࢥࢩࢻࡀ⢾౪୚య࡟ β ⤖ྜࢆ௓ࡋ࡚⤖ྜࡋ࡚࠸ࡿࡇ

࡜ࡀ♧ࡉࢀࡓ(Fig. 20)ࠋ

A.

B.

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39 .

Fig. 20 NMR spectrum of A) O-type trisaccharide41and B) Se-type trisaccharide.

ྜᡂࡋࡓ࢜࢟ࢧࢰࣜࣥయ62 ࡀࢩࣜ࢝ࢤࣝ࡟ࡼࡿᙅ㓟ᛶ᮲௳ୗ࡟࠾࠸࡚୙Ᏻᐃ࡛࠶ࡗࡓࡇ

࡜࠿ࡽࠊ⢾౪୚యࡢ୍㒊ࡀຍỈศゎ࡟ࡼࡾᾘ㈝ࡉࢀࡓ࡜⪃࠼ࠊEntry 2 ࡛ࡣ⢾౪୚యࡢᙜ㔞

NCOCH3 (6 H)

A)

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40 ࢆ࢔ࢡࢭࣉࢱ࣮࡟ᑐࡋ࡚30 ᙜ㔞࡟ቑࡸࡋࡓࠋࡋ࠿ࡋࠊ཯ᛂ㏿ᗘࡢቑຍࡣぢࡽࢀࡓࡀ཰⋡ࡣ Entry1 ࡜ྠ⛬ᗘ࡛࠶ࡗࡓࠋࡇࡢ⤖ᯝ࠿ࡽࠊ1.5 mU ࡢ Endo M ࡛ࡣࠊ⢾ཷᐜయ࡟ẚ࡭㓝⣲㔞ࡀ ᑡ࡞ࡃࠊ㌿⛣㏿ᗘࡼࡾศゎ㏿ᗘࡀ㏿࠸ࡢ࡛ࡣ࡞࠸࠿࡜ண᝿ࡋࠊEntry3 ࡛ࡣ㓝⣲㔞ࢆ 3.0 mU ࡟ቑࡸࡋ཯ᛂࢆ⾜ࡗࡓࠋࡑࡢ⤖ᯝࠊ཯ᛂࡣ2 ᫬㛫௨ෆ࡟⤊஢ࡋኚ᥮⋡ࡶ 90%࡜Ⰻዲ࡞ࡶࡢ ࡛࠶ࡗࡓ(Fig. 21)ࠋ

Reaction time: A) 0.5 h and B) 2.0 h Column: Inertsil ODS-3 (125×2.1 mm) Detection: UV detector (260 nm)

Eluent A:0.1% TFA aq. Eluent B: MeCN containing 0.1% TFA Eluent (Binary gradient 8% of eluent B, 1 mL/min) was employed.

A)

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41 ḟ࡟ࠊࣂࢵࣇ࢓࣮୰࡛ࡢᙅ㓟ᛶ᮲௳ୗ࡛࢜࢟ࢧࢰࣜࣥయ61 ࡀάᛶ໬ࡉࢀࡓ⤖ᯝࠊ⦰ྜ཯ ᛂࡀ⏕ࡌࡓྍ⬟ᛶࢆ⪃៖ࡋࠊEndo M ࢆ㝖࠸ࡓ࢜࢟ࢧࢰࣜࣥయ 61 ࡜⢾ཷᐜయ 69 ࢆᇵ㣴ࡋࡓ (Scheme 19)ࠋࡑࡢ⤖ᯝࠊ཯ᛂᚋ 18 ᫬㛫ࡢ᫬Ⅼ࡟࠾࠸࡚࢜࢟ࢧࢰࣜࣥయ 61 ࡢศゎࡢࡳࡀほ ᐹࡉࢀࠊHPLC ࡟ࡼࡿศᯒ࡛ࡣࠊ౪୚య࡟ኚ໬ࡣぢࡽࢀ࡞࠿ࡗࡓ(Fig. 22)ࠋࡇࢀࡽࡢࡇ࡜࠿ ࡽࠊࢭࣞࣀ໬⢾࢜࢟ࢧࢰࣜࣥయ61 ࡀ Endo M ࡢᇶ㉁࡜࡞ࡿࡇ࡜ࡀ᫂ࡽ࠿࡜࡞ࡗࡓࠋ Scheme 19 Fig. 22

Reaction time: 18 h.

Column: Inertsil ODS-3 (125×2.1 mm)

Eluent A:0.1% TFA aq. Eluent B: MeCN containing 0.1% TFA Eluent (Binary gradient 8% of eluent B, 1 mL/min) was employed.

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42

➨

➨஧㒊

ࡲ࡜ࡵ

➨஧㒊࡛ࡣࠊࢭࣞࣀ໬⢾ࡢ᭦࡞ࡿ㐺⏝⠊ᅖᣑ඘࡟ࡴࡅ࡚᪂ࡓ࡞⺮ⓑ㉁ᶆ㆑ἲ࡜ࡋ࡚⢾㌿ ⛣㓝⣲ࢆ⏝࠸ࡓ⺮ⓑ㉁ࡢࢭࣞࣀ໬⢾ಟ㣭ࢆᥦ᱌ࡋ◊✲࡟ྲྀࡾ⤌ࢇࡔࠋ⢾㌿⛣཯ᛂࡢᇶ㉁࡜ ࡋ࡚Se-Manβ(1-4)GlcNAc-oxa ࢆタィࡋࡓࠋ࣐ࣥࣀࢩࣝࢭࣞࣀࢩࢻ࡜࢞ࣛࢡࢺࢧ࣑ࣥㄏᑟయ ࡜ࡢ SN2 ཯ᛂ࡟ࡼࡾᇶᮏ㦵᱁ࢆᵓ⠏ࡋ࢜࢟ࢧࢰࣜࣥ࡜ࡋࡓᚋࠊ⬺ಖㆤࢆ⾜࠺ࡇ࡜࡛⡆౽࡟ ྜᡂࡋࡓࠋࡲࡓࠊࢭࣞࣀ໬⢾࢜࢟ࢧࢰࣜࣥయࢆ⢾౪୚యࠊGlcNAc-pNP ࢆ⢾ཷᐜయ࡜ࡋ࡚⏝ ࠸ࡓ⢾㌿⛣཯ᛂ࡬࡜౪ࡋࡓ⤖ᯝࠊ㌿⛣య⏕ᡂ≀ࢆᚓࡽࢀࠊ⢾࢜࢟ࢧࢰࣜࣥయࡀ⢾㌿⛣㓝⣲ ࡢᇶ㉁࡜࡞ࡿࡇ࡜ࡀ᫂ࡽ࠿࡜࡞ࡗࡓࠋ௒ᚋࡣࠊ⺮ⓑ㉁࡬ࡢᑟධ࠾ࡼࡧᵓ㐀ࡢྠ୍ᛶࡢ☜ㄆ ࢆ⾜ࡗ࡚࠸ࡃࠋ

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43

⥲

⥲ᣓ

1828 ᖺ Wöhler ࡀ↓ᶵ≀࡛࠶ࡿࢩ࢔ࣥ࢞ࢫ࡜࢔ࣥࣔࢽ࢔࠿ࡽᒀ⣲ࢆྜᡂࡋࡓࡇ࡜࠿ࡽጞࡲ ࡗࡓ᭷ᶵྜᡂ໬Ꮫࡣࠊ௒ࡸᡭ㛫ࡸ㈝⏝ࢆ࠿ࡅࢀࡤ࡝ࢇ࡞࡟」㞧࡞ኳ↛≀࡛࠶ࢁ࠺ࡀྜᡂ࡛ ࡁ࡞࠸ࡶࡢࡣ࡞࠸࡜࠸ࢃࢀ࡚ஂࡋ࠸ࠋࡇࡢࡼ࠺࡞᝟ໃࡢ࡞࠿࡛ࠊ᭷ᶵ໬Ꮫ࡟௒ᚋࡲࡍࡲࡍ ồࡵࡽࢀࡿࡢࡣࠊప⎔ቃ㈇Ⲵᆺࡢ㧗ຠ⋡ⓗ࡞ྜᡂἲࡢ☜❧ࡸ⏕࿨⌧㇟ࡢゎ᫂࡟ྥࡅࡓேᕤ ศᏊࡢྜᡂ࡛࠶ࡿᛮࢃࢀࡿࠋᮏ◊✲࡛ࡣࠊᚋ⪅࡟ศ㢮ࡉࢀࡿ⺮ⓑ㉁ࡢ❧యᵓ㐀ゎᯒࢆ㎿㏿ ໬ࡍࡿ㠀ኳ↛ᆺࢭࣞࣀ໬⢾ࡢྜᡂ࠾ࡼࡧ᪂つ฼⏝࡟ྥࡅࡓᇶ♏ⓗ◊✲ࢆሗ࿌ࡋࡓࠋ➨୍㒊 ࡛ࡣࠊከᵝ࡞⢾ㄆ㆑⺮ⓑ㉁࡟ᑐᛂࡍࡿࡓࡵ࡟ࢭࣞࣥᑟධ⟠ᡤࡀ␗࡞ࡿ໬ྜ≀⩌(ࢭࣞࣀ໬ࣇ ࢥ࣮ࢫㄏᑟయ⩌)ࡀ᭷ຠ࡛࠶ࡿ࡜╔᝿ࡋࠊࡑࡢྜᡂ࠾ࡼࡧ❧యᵓ㐀ࡀᮍゎ࡛᫂࠶ࡗࡓ⺮ⓑ㉁ ࡢ❧యᵓ㐀ゎᯒࢆ⾜࠸ࡑࡢᡭἲࡢ᭷⏝ᛶࢆ♧ࡋࡓࠋࡇࡢ⤖ᯝࡣࠊ᪤Ꮡࡢ⤖ᬗ໬ࣟ࣎ࢵࢺࢆ ే⏝ࡍࡿࡇ࡜࡛」ᩘࡢ⢾ㄆ㆑⺮ⓑ㉁ࡢ⥙⨶ⓗ࡞❧యᵓ㐀ゎᯒࡢᐇ⾜ྍ⬟ᛶࢆ♧၀ࡍࡿࡓࡵࠊ ௒ᚋࡢⓎᒎ࡟ᮇᚅࡀᣢࡓࢀࡿࠋࡲࡓࠊ➨஧㒊࡛ࡣࢭࣞࣀ໬⢾ࡢ᭦࡞ࡿᛂ⏝ࢆ┠ᣦࡋࠊࢭࣞ ࣀ໬⢾࢜࢟ࢧࢰࣜࣥయࡢྜᡂ࠾ࡼࡧࡑࢀࢆᇶ㉁࡜ࡋࡓ㓝⣲⢾㌿⛣཯ᛂࡢ᳨ドࢆ⾜ࡗࡓࠋᮏ ◊✲࡛ᚓࡽࢀࡓ⤖ᯝࡼࡾ⢾⺮ⓑ㉁ࡢࢭࣞࣀ໬⢾ಟ㣭ࡢྍ⬟ᛶࡀ♧ࡉࢀࠊ⺮ⓑ㉁ୖࡢ⢾㙐ᵓ 㐀ࡢᚤᑠ୙ᆒ୍ᛶ࡟ࡼࡾ❧ࡕ㐜ࢀ࡚࠸ࡿ⢾⺮ⓑ㉁ࡢ⤖ᬗᵓ㐀ゎᯒࡢ㎿㏿໬ࡀぢ㎸ࡲࢀࡿࠋ ࡲࡓࠊࡇࡢᡭἲ࡟ࡼࡾࢭࣞࣀ࣓ࢳ࢜ࢽࣥᶆ㆑ヨᩱࡢㄪ〇ࡀᅔ㞴࡞⺮ⓑ㉁ࡢࢭࣞࣥᶆ㆑໬࠾ ࡼࡧX ⥺⤖ᬗᵓ㐀ゎᯒࡀྍ⬟࡟࡞ࡿ࡜ᮇᚅࡉࢀࡿࠋ ᮏ◊✲࡛ᚓࡽࢀࡓ▱ぢࡀ௒ᚋࠊX ⥺⤖ᬗᵓ㐀ゎᯒࢆྵࡴ⺮ⓑ㉁ࡢ❧యᵓ㐀ゎᯒ࡟ᑡࡋ࡛ࡶ ᙺ࡟❧࡚ࢀࡤᖾ࠸࡛࠶ࡿࠋ

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44

ᐇ

ᐇ㦂ࡢ㒊

୍⯡᧯స

1_Hࠊ77_Seࠊ13_{C NMR ࢫ࣌ࢡࢺࣝࡣ Bruker Avance III 500 ࢆ⏝࠸࡚ ᐃࡋࡓࠋ}1_{H NMR ࡢࢣ࣑}

࢝ࣝࢩࣇࢺࡣෆ㒊ᶆ‽≀㉁ (Me4Si) ࡟ᑐࡍࡿ┦ᑐ್ ppm (δ) ࡜ࡋ࡚⾲ࡋࡓࠋࡲࡓࠊ77Se ࡜

13_{C NMR ࡢࢣ࣑࢝ࣝࢩࣇࢺࡣࡑࢀࡒࢀࠊ⁐፹࠾ࡼࡧእ㒊ᶆ‽࡟ᑐࡍࡿ┦ᑐ್ ppm (δ)࡜ࡋ࡚}

⾲ࡋࡓࠋ௨ୗࡢ␎⛠ࡣከ㔜ᗘࢆ⾲ࡍࡢ࡟⏝࠸ࡓ (s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br = broad)ࠋ㉁㔞ศᯒ (HRMS) ࡣࠊBruker Daltonics micrOTOF (ESI-TOF) ࢆ⏝

࠸࡚ ᐃࡋࡓࠋẚ᪕ගᗘࡣ Horiba SEPA-300 㧗ឤᗘ᪕ගගᗘィࢆ⏝࠸࡚ ᐃࡋࡓࠋ ᐃ࡟

౑⏝ࡋࡓ⁐፹࡜⃰ᗘࡣ ( ) ෆ࡟♧ࡋࡓࠋ࣮ࣔࣞ࢟ࣗࣛࢩ࣮ࣈࡣ Wako Chemicals Inc. ࡢࡶࡢ

ࢆࠊ300 °C ࡟࡚ 2 ᫬㛫άᛶ໬ࡉࡏ࡚࠿ࡽ⏝࠸ࡓࠋ཯ᛂ࡟⏝࠸ࡓ⁐፹ࡣ MS4Åࠊ࠾ࡼࡧ MSAW-300 ࡛ணࡵ஝⇱ࡉࡏࡓࡶࡢࢆ⏝࠸ࡓࠋ཯ᛂࡣ࢔ࣝࢦࣥ࢞ࢫ㞺ᅖẼୗ࡛⾜ࡗࡓࠋTLC

ศᯒ࡟ࡣMerck TLC (silica gel 60F254 on glass)ࢆ⏝࠸ࠊ໬ྜ≀ࡢ᳨ฟ࡟ࡣ UV ↷ᑕ (254 nm)ࠊ

10 %◲㓟-࢚ࢱࣀ࣮ࣝ⁐ᾮࠊ20 %ࣜࣥࣔࣜࣈࢹࣥ㓟-࢚ࢱࣀ࣮ࣝ⁐ᾮࠊࢽࣥࣄࢻࣜࣥヨ⸆ࢆ⏝ ࠸ࡓࠋࣇࣛࢵࢩࣗࢩࣜ࢝ࢤ࣒ࣝ࢝ࣛࢡ࣐ࣟࢺࢢࣛࣇ࢕࣮࡟ࡣ (Fuji Silysia Co., 80 mesh and 300 mesh)ࠊ࠶ࡿ࠸ࡣ Sephadex (Pharmacia LH-20)ࢆ⏝࠸ࠊ౑⏝ࡋࡓ⁐ฟ⁐፹ࡣయ✚ẚ (v/v) ࡛♧ࡋࡓࠋ඲࡚ࡢ⃰⦰᧯సࡣ‮ᾎ࡟ࡼࡿຍ ࡜ῶᅽ᮲௳໬࡛⾜ࡗࡓࠋ

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Methyl 3,4-di-O-acetyl-6-deoxy-2-O-(4-methoxybenzyl)-1-seleno-α-L-galactopyranoside (8α) and -β-L-galactopyranoside (8β)

࢔ࣝࢦࣥ㞺ᅖẼୗࠊࢭࣞࣀ࢔ࢭࢱ࣮ࣝ7 (100 mg, 463 μmol)ࠊࣇࢥࢩࣝ࢖࣑ࢹ࣮ࢺ 6 (50.0 mg,

90.0 μmol)ࠊ࠾ࡼࡧ AW-300 (90 mg)ࢆ CH2Cl2-TBME (925 μL, 1:2)࡟ᠱ⃮ࡉࡏࠊᐊ ࡛ 1 ᫬㛫

᧠ᢾࡋࡓࠋ⁐ᾮࢆ-78 °C ࡬෭༷ᚋࠊTMSOTf (10.2 μL, 99.6 μmol)ࢆຍ࠼࡚ 21 ᫬㛫᧠ᢾࡋࡓࠋ ཯ᛂ⤊஢ࢆTLC (EtOAc/Toluene = 1/8)࡛☜ㄆᚋࠊtriethylamine (500 μL)ࢆຍ࠼࡚཯ᛂࢆ೵Ṇࡋࠊ ᅛᙧ≀ࢆࢭࣛ࢖ࢺ࡟࡚ℐูࡋࠊCHl2Cl2࡛Ὑίࡋࡓࠋࢁᾮࢆ⃰⦰ᚋࠊṧ´ࢆࢩࣜ࢝ࢤࣝ࢝ࣛ ࣒ࢡ࣐ࣟࢺࢢࣛࣇ࢕࣮ (EtOAc/Toluene = 1/30) ࡛⢭〇ࡋ໬ྜ≀ 8α (27.3 mg, 66%) ࠾ࡼࡧ 8β (9.3 mg, 21%)ࢆ㯤Ⰽ⢓ᛶᾮయ࡜ࡋ࡚ᚓࡓࠋα-isomer (8α); [α]D -165.2 ° (c 1.0, CHCl3); 1H NMR (500 MHz, CDCl3) δ 7.27-6.87 (2 d, 4 H, Ar), 5.87 (d, 1 H, J1,2 = 5.5 Hz, H-1), 5.29 (d, 1 H, J3,4 =

3.0 Hz, H-4), 5.16 (dd, 1 H, J2,3 = 10.5 Hz, H-3), 4.64 (d, 1 H, Jgem = 12.0 Hz, OCH2Ar), 4.49 (d, 1

H, Jgem = 12.0 Hz, OCH2Ar), 4.37 (m, 1 H, H-5), 3.97 (dd, 1 H, H-2), 3.80 (s, 3 H, OCH3), 2.14-1.98

(2 s, 6 H, 2 Ac), 1.90 (s, 3 H, SeCH3), 1.15 (d, 3 H, J5,6 = 6.5 Hz, H-6); 13C NMR (125 MHz, CDCl3)

δ 170.4, 170.0, 159.4, 129.7, 129.3, 113.8, 80.8, 72.9, 71.8, 71.4, 71.0, 66.2, 55.3, 20.8, 16.0, 1.63;

77_{Se NMR (94 MHz, CDCl}

3) δ 91.3; HRMS (ESI) m/z: found [M+Na]+ 469.0736, C19H26O7Se calcd

for [M+Na]+_{469.0736. β-isomer (8β); [α]}

D +3.6 ° (c 0.8, CHCl3); 1H NMR (500 MHz, CDCl3) δ

7.27-6.86 (2 d, 4 H, Ar), 5.27 (dd, 1 H, J3,4 = 3.0 Hz, J4,5 = 0.5 Hz, H-4), 4.98 (dd, 1 H, J2,3 = 9.5 Hz,

H-3), 4.75 (d, 1 H, Jgem = 10.5 Hz, OCH2Ar), 4.66 (d, 1 H, J1,2 = 9.5 Hz, H-1), 4.59 (d, 1 H, Jgem =

10.0 Hz, OCH2Ar), 3.79-3.71 (m, 5 H, CH3, H-2, H-5), 2.17-1.99 (3 s, 9 H, 2 Ac, SeCH3), 1.38 (d, 3

H, J5,6 = 6.5 Hz, H-6); 13C NMR (125 MHz, CDCl3): δ 170.4, 170.1, 159.6, 130.1, 129.8, 113.9, 79.0,

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HRMS (ESI) m/z: found [M+Na]+ 469.0736, C19H26O7Se calcd for [M+Na]+ 469.0736.

Methyl 3,4-di-O-acetyl-6-deoxy-1-seleno-α-L-galactopyranoside (9α)

࢔ࣝࢦࣥ㞺ᅖẼୗࠊ໬ྜ≀8α (30 mg, 70 μmol)࠾ࡼࡧ anisole (15 mg, 140 μmol)ࢆ CH2Cl2 (0.92

mL )࡟⁐ゎࡉࡏ-20 °C ࡟෭༷ࡋࡓࠋTrifluoroacetic acid (0.46 mL)ࢆຍ࠼࡚ྠ ᗘ᮲௳࡛ 6 ᫬ 㛫ᨩᢾࡋࡓࠋ཯ᛂ⤊஢ࢆTLC (EtOAc/n-Hexane = 1/1)࡛☜ㄆᚋࠊࢺ࢚ࣝࣥඹἛࢆ⾜ࡗࡓࠋṧ ´ࢆࢩࣜ࢝ࢤ࣒ࣝ࢝ࣛࢡ࣐ࣟࢺࢢࣛࣇ࢕࣮ (EtOAc/n-Hexane = 1/2)࡛⢭〇ࡋ໬ྜ≀ 9α (21 mg, 90%)ࢆ㯤Ⰽ⢓ᛶᾮయ࡜ࡋ࡚ᚓࡓࠋ[α]D -273.2 ° (c 1.0, CHCl3); 1H NMR (500 MHz, CDCl3) δ 5.71 (d, 1 H, J1,2 = 5.5 Hz, H-1), 5.26 (dd, 1 H, J3,4 = 3.0 Hz, J4,5 = 1.0 Hz, H-4), 4.91 (dd, 1 H, J2,3 = 10.0 Hz, H-3), 4.34 (m, 1 H, H-5), 4.13 (m, 1 H, H-2), 2.16-2.05 (3 s, 9 H, 2 Ac, SeCH3), 1.18 (d, 3 H, J5,6 = 6.5 Hz, H-6); 13C NMR (125 MHz, CDCl3) δ 171.0, 170.8, 86.9, 73.2, 71.1, 67.9, 67.4, 21.4, 21.0, 16.3, 4.3; 77_{Se NMR (94 MHz, CDCl}

3) δ 75.2; HRMS (ESI) m/z: found [M+Na]+ 349.0161,

C11H18O6Se calcd for [M+Na]+ 349.0161.

Methyl 1-seleno-α-L-galactopyranoside (1α)

໬ྜ≀ 9α (16.0 mg, 49.0 μmol) ࢆ MeOH (500 μL)࡟⁐ゎࡉࡏ Sodium methoxide (28% in MeOH, 2.00 mg, 10.0 μmol) ࢆ ຍ ࠼ ࠊ ᐊ ࡟ ࡚ 20 ศ 㛫 ᧠ ᢾ ࡋ ࡓ ࠋ ཯ ᛂ ⤊ ஢ ࢆ TLC

(MeOH/Toluene = 1/5)࡛☜ㄆᚋࠊMuromac (H+) ࢆ⏝࠸࡚୰࿴ࡋࡓࠋᅛᙧ≀ࢆ⬺⬡⥥࡟࡚ℐู

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࢕࣮ Sephadex LH-20 (H2O/MeOH = 1/4) ࡛⢭〇ࡋ໬ྜ≀ 1α (10.6 mg, 89%) ࢆⓑⰍಶయ࡜ࡋ

࡚ᚓࡓࠋ[α]D -327.6 ° (c 0.8, MeOH); 1H NMR (500 MHz, CD3OD) δ 4.51 (dd, 1 H, J1,2 = 9.5 Hz,

H-1), 3.70-3.61 (m, 3 H, H-2, H-4, H-5), 3.47 (dd, 1 H, J3,4 = 3.5 Hz, H-3), 2.10 (s, 3 H, SeCH3),

1.28 (d, 3 H, J5,6 = 6.5 Hz, H-6); 13C NMR (125 MHz, CD3OD) δ 85.3, 73.2, 73.2, 69.9, 69.4, 16.6,

1.4; 77Se NMR (94 MHz, CD3OD) 75.4; HRMS (ESI) m/z: found [M+Na]+ 264.9948, C7H14O4Se

calcd for [M+Na]+_264.9950.

Methyl 3,4-di-O-acetyl-6-deoxy-1-seleno-β-L-galactopyranoside (9β)

࢔ࣝࢦࣥ㞺ᅖẼୗࠊ໬ྜ≀8β (64 mg, 140 μmol)࠾ࡼࡧ anisole (31 μL, 290 μmol)ࢆ CH2Cl2 (1.9

mL)࡟⁐ゎࡉࡏ-40 °C ࡟෭༷ࡋࡓࠋ Trifluoroacetic acid (0.46 mL)ࢆຍ࠼࡚ྠ ᗘ᮲௳࡛ 5 ᫬

㛫ᨩᢾࡋࡓࠋ཯ᛂ⤊஢ࢆTLC (MeOH/CHCl3 = 1/20)࡛☜ㄆᚋࠊࢺ࢚ࣝࣥඹἛࢆ⾜࠸ࠊṧ´ࢆ

ࢩࣜ࢝ࢤ࣒ࣝ࢝ࣛࢡ࣐ࣟࢺࢢࣛࣇ࢕࣮ (EtOAc/n-Hexane = 1/2) ࡛⢭〇ࡋ໬ྜ≀ 9β (40 mg,

86%)ࢆ㯤Ⰽ⢓ᛶᾮయ࡜ࡋ࡚ᚓࡓࠋ[α]D -6.6 ° (c 0.8, CHCl3); 1H NMR (500 MHz, CDCl3) δ 5.27

(d, 1 H, J3,4 = 3.0 Hz, H-4), 4.93 (dd, 1 H, J2,3 = 9.5 Hz, H-3), 4.60 (d, 1 H, J1,2 = 10.0 Hz, H-1),

3.90-3.83 (m, 2 H, H-2, H-5), 2.47 (d, 1 H, J2,OH = 2.0 Hz, OH), 2.16-2.06 (3 s , 9 H, 2 Ac, SeCH3),

1.21 (d, 3 H, J5,6 = 6.5 Hz, H-6); 13C NMR (125 MHz, CDCl3) δ 168.4, 79.3, 78.9, 72.3, 71.8, 68.7,

65.6, 65.5, 18.7, 18.5, 14.3; 77_{Se NMR (94 MHz, CDCl}

3) δ 177.9; HRMS (ESI) m/z: found [M+Na]+

349.0161, C11H18O6Se calcd for [M+Na]+ 349.0161.

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໬ྜ≀ 9β (40 mg, 120 μmol) ࢆ MeOH (4.1 mL)࡟⁐ゎࡉࡏ Sodium methoxide (28% in MeOH,

10 mg, 40 μmol)ࢆຍ࠼ࠊᐊ ࡟࡚ 30 ศ㛫᧠ᢾࡋࡓࠋ཯ᛂ⤊஢ࢆ TLC (MeOH/Toluene = 1/5) ࡛☜ㄆᚋࠊMuromac (H+)ࢆ⏝࠸࡚୰࿴ࡋࡓࠋᅛᙧ≀ࢆࢁ㐣ࡋࠊ࣓ࢱࣀ࣮࡛ࣝὙίᚋࠊࢁᾮࢆ ⃰⦰ࡋࠊᚓࡽࢀࡓṧ´ࢆࢤࣝℐ㐣ࢡ࣐ࣟࢺࢢࣛࣇ࢕࣮ Sephadex LH-20 (H2O/MeOH = 1/4)࡛ ⢭〇ࡋ໬ྜ≀1β (30 mg, quant.)ࢆⓑⰍಶయ࡜ࡋ࡚ᚓࡓࠋ[α]D +21.9 ° (c 0.8, MeOH); 1H NMR (500 MHz, CD3OD) δ 4.51 (dd, 1 H, J1,2 = 9.5 Hz, H-1), 3.70-3.61 (m, 3 H, H-2, H-4, H-5), 3.47 (dd, 1 H, J2,3 = 9.5 Hz, J3,4 = 3.5 Hz, H-3), 2.10 (s, 3 H, SeCH3), 1.28 (d, 3 H, J5,6 = 6.5 Hz, H-6); 13C NMR (125 MHz, CD3OD) δ 110.0, 105.3, 104.2, 101.3, 99.7, 45.0, 29.7; 77Se NMR (94 MHz,

CD3OD) δ 190.4; HRMS (ESI) m/z: found [M+Na]+ 264.9948, C7H14O4Se calcd for [M+Na]+

264.9950.

Methyl 2,6-dideoxy-3,4-O-isopropylidene-2-(4-methylbenzoylseleno)-α-L-galactopyranoside (24)

࢔ࣝࢦࣥ㞺ᅖẼୗࠊ໬ྜ≀21 (96.0 mg, 440 μmol)ࡢ CH2Cl2 (10.0 mL)⁐ᾮ࡟ࠊpyridine (148 μL,

183 μmol)࠾ࡼࡧ trifluoromethanesulfonic anhydride (154 μL, 916 μmol)ࢆ -20 °C ࡟࡚ຍ࠼ 30

ศ㛫ᐊ ࡛᧠ᢾࡋࡓࠋ཯ᛂ⤊஢ࢆTLC (EtOAc/n-Hexane = 1/1)࡛☜ㄆࡋࠊCH2Cl2࡛ᕼ㔘ᚋࠊ

Ὑί(2M-ሷ㓟ࠊ⵨␃Ỉࠊ㣬࿴Ⅳ㓟Ỉ⣲ࢼࢺ࣒ࣜ࢘Ỉ⁐ᾮࠊ㣬࿴㣗ሷỈ)ࠊ஝⇱ (↓Ỉ◲㓟ࢼ

ࢺ࣒ࣜ࢘)ࠊ⁐፹␃ཤᚋࠊ┿✵ࣛ࢖ࣥ࡟࡚ 3 ᫬㛫஝⇱ࡋࡓࠋᚓࡽࢀࡓࢺࣜࣇ࣮ࣛࢺయࢆ⬺Ẽ

ࡋࡓDMA (3.60 mL)࡟⁐ゎࡉࡏࡓࠋ཯ᛂ⁐ᾮ࡟ 4-methylselenobenzoic anhydride 23 (788 mg,

2.48 mmol)ࠊN,N-diisopropylethylamine (444 μL, 2.48 mmol)ࡑࡋ࡚ piperidine (244 μL, 2.48 mmol) ࡢ DMA (6.40 mL)⁐ᾮࢆ⁲ୗ࡟࡚ຍ࠼ࠊ90 °C ࡟࡚ 75 ศ㛫᧠ᢾࡋࡓࠋ཯ᛂ⤊஢ࢆ TLC

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(EtOAc/n-Hexane = 1/3)࡛☜ㄆᚋࠊᕼ㔘(EtOAc)ࠊὙί(2M-ሷ㓟ࠊH2Oࠊ㣬࿴Ⅳ㓟Ỉ⣲ࢼࢺࣜ

࣒࢘Ỉ⁐ᾮࠊ㣬࿴㣗ሷỈ)ࠊ஝⇱(↓Ỉ◲㓟ࢼࢺ࣒ࣜ࢘)ࠊ⁐፹␃ཤࢆ⾜ࡗࡓࠋṧ´ࢆࢩࣜ࢝ ࢤ࣒ࣝ࢝ࣛࢡ࣐ࣟࢺࢢࣛࣇ࢕࣮ (EtOAc/toluene = 1/5)࡛⢭〇ࡋ໬ྜ≀ 24 (163 mg, 93%)ࢆ㯤 Ⰽ⢓ᛶᾮయ࡜ࡋ࡚ᚓࡓࠋ[α]D -66.0 ° (c 1.1, CHCl3); 1H NMR (500 MHz, CDCl3) δ 7.81-7.24 (2 d, 4 H, Ar), 4.76 (d, 1 H, J1,2 = 3.5 Hz, H-1), 4.38 (dd, 1 H, J2,3 = 11.0 Hz, J3,4 = 5.0 Hz, H-3), 4.16 (m, 1 H, H-5), 4.04 (dd, 1 H, J4,5 = 2.0 Hz, H-4), 3.94 (dd, 1 H, H-2), 3.37 (s, 3 H, OCH3), 2.39 (s, 3 H, Ar-CH3), 1.63 (s, 3 H, (CH3)2C), 1.41 (d, 3 H, J5,6 = 6.5 Hz, H-6), 1.36 (s, 3 H, (CH3)2C); 13C NMR (125 MHz, CDCl3) δ 192.5, 144.6, 136.2, 129.4, 127.5, 109.4, 109.1, 101.3, 75.9, 74.4, 63.1, 55.7, 44.9, 29.7, 28.1, 26.5, 21.7, 16.7; 77Se NMR (94 MHz, CDCl3) δ 534.0; HRMS (ESI) m/z: found [M+Na]+_{423.0681, C}

18H24O5Se calcd for [M+Na]+ 423.0681.

Methyl 2,6-dideoxy-3,4-O-isopropylidene-2-methylseleno-α-L-galactopyranoside (25)

࢔ࣝࢦࣥ㞺ᅖẼୗࠊ໬ྜ≀24 (60 mg, 150 μmol)ࢆ⬺Ẽࡋࡓ DMF (2.0 mL)࡟⁐ゎࡉࡏࠊCs2CO3

(98 mg, 300 μmol)ࠊN-methylhydrazine (12.0 mg, 230 μmol)ࡑࡋ࡚ methyl iodide (19.0 μL, 300 μmol) ࢆᐊ ࡛ຍ࠼ 70 ศ㛫᧠ᢾࡋࡓࠋ཯ᛂ⤊஢ࢆ TLC (EtOAc/n-Hexane = 1/3)࡛☜ㄆᚋࠊᕼ 㔘(EtOAc)ࠊὙί(㣬࿴Ⅳ㓟Ỉ⣲ࢼࢺ࣒ࣜ࢘Ỉ⁐ᾮࠊ㣬࿴㣗ሷỈ)ࠊ஝⇱(↓Ỉ◲㓟ࢼࢺ࣒ࣜ࢘)ࠊ ⁐፹␃ཤࢆ⾜ࡗࡓࠋᚓࡽࢀࡓṧ´ࢆࢩࣜ࢝ࢤ࣒ࣝ࢝ࣛࢡ࣐ࣟࢺࢢࣛࣇ࢕࣮ (EtOAc/n-Hexane = 1/6)࡛⢭〇ࡋ໬ྜ≀ 25 (29 mg, 64%)ࢆ㯤Ⰽ⢓ᛶᾮయ࡜ࡋ࡚ᚓࡓࠋ[α]D -141.7 ° (c 1.1, CHCl3); 1_{H NMR (500 MHz, CDCl} 3) δ 4.81 (d, 1 H, J1,2 = 3.0 Hz, H-1), 4.43 (dd, 1 H, J2,3 = 9.5 Hz, J3,4 = 5.0 Hz, H-3), 4.11 (m, 1 H, H-5), 3.96 (dd, 1 H, J4,5 = 2.5 Hz, H-4), 3.36 (s, 3 H, OCH3), 2.82 (dd, 1 H, H-2), 2.14 (s, 3 H, SeCH3), 1.52-1.36 (m, 9 H, (CH3)2C, H-6); 13C NMR (125 MHz, CDCl3) δ

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108.7, 101.6, 75.7, 62.8, 55.6, 43.1, 29.7, 28.6, 26.4, 16.7, 4.6; 77Se NMR (94 MHz, CDCl3) δ 127.2;

HRMS (ESI) m/z: found [M+Na]+ 319.0419, C11H20O4Se calcd for [M+Na]+ 319.0419.

Methyl 2,6-dideoxy-2-methylseleno-α-L-galactopyranoside (2)

໬ྜ≀25 (10 mg, 34 μmol)ࢆ H2O (67 μL)࡟ᠱ⃮ࡉࡏࠊ0 °C ࡛ Acetic acid (270 μL)ࢆຍ࠼ࠊ50 °C

࡛50 ศ㛫᧠ᢾࡋࡓࠋ཯ᛂࡢ⤊஢ࢆ TLC (MeOH/CHCl3 = 1/10)࡛☜ㄆᚋࠊࢺ࢚ࣝࣥඹἛࢆ⾜ ࡗࡓࠋṧ´ࢆࢩࣜ࢝ࢤ࣒ࣝ࢝ࣛࢡ࣐ࣟࢺࢢࣛࣇ࢕࣮ (EtOAc/Toluene = 2/1)࡛⢭〇ࡋ໬ྜ≀ 2 (7.2 mg, 83%) ࢆⓑⰍಶయ࡜ࡋ࡚ᚓࡓࠋ[α]D +21.9 ° (c 0.8, MeOH); 1H NMR (500 MHz, CD3OD) δ 4.77 (d, 1 H, J1,2 = 3.5 Hz, H-1), 3.91-3.84 (m, 2 H, H-3, H-5), 3.61 (d, 1 H, J3,4 = 2.5 Hz, H-4), 3.31 (s, 3 H, OCH3), 2.96 (dd, 1 H, J2,3 = 11.0 Hz, H-2), 2.06 (s, 3 H, SeCH3), 1.21 (d, 3 H, J5,6 = 6.5 Hz, H-6); 13C NMR (125 MHz, CD3OD) δ 103.3, 73.5, 72.5, 67.7, 55.8, 44.9, 16.9, 4.8; 77Se NMR

(94 MHz, CD3OD) δ 102.8; HRMS (ESI) m/z: found [M+Na]+ 279.0106, C8H16O4Se calcd for

[M+Na]+ 279.0106.

Methyl 4-O-acetyl-6-deoxy-2-methoxymethyl-α-L-galactopyranoside (31)

࢔ࣝࢦࣥ㞺ᅖẼୗࠊ໬ྜ≀10 (2.44g, 13.7 mmol)ࢆ MeCN (137 mL)࡟⁐ゎࡉࡏࠊ0 °C ࡛ triethyl

orthoformate (3.80 mL, 20.6 mmol)࡜ CSA (325 mg, 1.40 mmol)ࢆຍ࠼ࠊᐊ ࡛ 7 ᫬㛫᧠ᢾࡋࡓࠋ

཯ᛂ⤊஢ࢆTLC (MeOH/CHCl3 = 10/1)࡛☜ㄆᚋࠊ0 ˚C ࡛ triethylamine ࢆຍ࠼཯ᛂࢆ೵Ṇࡉࡏ

(54)

51

࡛28 ᫬㛫᧠ᢾࡋࡓࠋ཯ᛂ⤊஢ࢆ TLC (EtOAc/n-Hexane = 1/1)࡟࡚☜ㄆᚋࠊMeOH ࢆຍ࠼࡚཯

ᛂࢆ೵Ṇࡉࡏࡓࠋ2M-ሷ㓟ࢆຍ࠼ᐊ ࡛ 10 ศ㛫᧠ᢾࡋࠊ࢜ࣝࢯ࢚ࢫࢸࣝࡢຍỈศゎࢆ TLC

(EtOAc/n-Hexane = 1/1)࡟࡚☜ㄆᚋࠊᕼ㔘(EtOAc)ࠊὙί (2M-ሷ㓟ࠊH2Oࠊ㣬࿴Ⅳ㓟Ỉ⣲ࢼࢺ

࣒ࣜ࢘Ỉ⁐ᾮࠊ㣬࿴㣗ሷỈ)ࠊ஝⇱(↓Ỉ◲㓟ࢼࢺ࣒ࣜ࢘)ࠊ⁐፹␃ཤࢆ⾜ࡗࡓࠋṧ´ࢆࢩࣜ

࢝ࢤ࣒ࣝ࢝ࣛࢡ࣐ࣟࢺࢢࣛࣇ࢕࣮ (EtOAc/Toluene = 1/5) ࡛⢭〇ࡋ໬ྜ≀ 31 (2.97 g, 82%)ࢆ

↓Ⰽ⢓ᛶᾮయ࡜ࡋ࡚ᚓࡓࠋ[α]D -28.9 ° (c 0.4, CHCl3); 1H NMR (500 MHz, CDCl3) δ 5.27 (dd, 1 H,

J3,4 = 3.5 Hz, J4,5 = 1.0 Hz, H-4), 4.84 (d, 1 H, J1,2 = 3.5 Hz, H-1), 4.82 (d, 1 H, Jgem = 12.0 Hz,

OCH2OCH3), 4.73 (d, 1 H, Jgem = 12.0 Hz, OCH2OCH3), 4.12-4.04 (m, 2 H, H-3, H-5), 3.72 (dd, 1 H,

J2,3 = 10.0 Hz, H-2), 3.43-3.41 (m, 6 H, 2 OCH3), 3.01 (s, 1 H, OH), 2.18 (s, 3 H, Ac), 1.16 (d, 3 H,

J5,6 = 6.5 Hz, H-6); 13C NMR (125 MHz, CDCl3) δ 177.2, 99.3, 98.1, 78.3, 73.0, 67.6, 64.5, 55.9,

55.3, 20.9, 16.2; HRMS (ESI) m/z: found [M+Na]+ 287.1103, C11H20O7 calcd for [M+Na]+

287.1101.

Methyl 4-O-acetyl-6-deoxy-2-O-methoxymethyl-α-L-xylo-hexopyranosid-3-ulose (32)

࢔ࣝࢦࣥ㞺ᅖẼୗࠊ໬ྜ≀31 (620 mg, 2.35 mmol) ࡜ NaHCO3 (983 mg, 11.7 mmol) ࢆ CH2Cl2

(23.5 mL)࡟ᠱ⃮ࡉࡏࠊ0 °C ࡛ Dess-Martin periodinane (1.29 g, 3.05 mmol) ࢆຍ࠼࡚ᐊ ࡛ 18

᫬㛫᧠ᢾࡋࡓࠋ཯ᛂ⤊஢ࢆTLC (EtOAc/n-Hexane = 2/1)࡟࡚᧠ᢾᚋࠊᕼ㔘(Et2O)ࡋࠊsatd aq.

Na2S2O3ࢆຍ࠼཯ᛂࢆ೵ṆࡉࡏࡓࠋỈᒙࢆEt2O ࡛ᢳฟᚋࠊὙί(㣬࿴㣗ሷỈ)ࠊ஝⇱ (↓Ỉ◲

㓟 ࢼ ࢺ ࣜ ࢘ ࣒)ࠊ⁐ ፹ ␃ཤ ࢆ ⾜ ࡗࡓ ࠋṧ ´ ࢆࢩࣜ ࢝ ࢤࣝ ࢝ ࣒ࣛ ࢡ ࣐ࣟࢺ ࢢ ࣛࣇ ࢕࣮

(Acetone/Toluene = 1/5) ࡛⢭〇ࡋ໬ྜ≀ 32 (449 mg, 73%) ࢆ↓Ⰽ⢓ᛶᾮయ࡜ࡋ࡚ᚓࡓࠋ[α]D

+3.0 ° (c 0.7, CHCl3); 1H NMR (500 MHz, CDCl3) δ 5.11 (d, 1 H, J1,2 = 4.0 Hz, H-1), 5.08 (d, 1 H,

(55)

52

H, 2 OCH3), 2.19 (s, 3 H, Ac), 1.27 (d, 3 H, J5,6 = 6.5 Hz, H-6); 13C NMR (125 MHz, CDCl3) δ

197.8, 169.6, 101.8, 96.5, 78.9, 77.4, 67.7, 56.0, 55.7, 20.7, 15.6; HRMS (ESI) m/z: found [M+Na]+ 285.0945, C11H18O7 calcd for [M+Na]+ 285.0945.

Methyl 4-O-acetyl-6-deoxy-2-O-methoxymethyl-α-L-gulopyranoside (33)

࢔ࣝࢦࣥ㞺ᅖẼୗࠊ໬ྜ≀32 (50 mg, 0.19 mmol)ࡢ MeOH (1.9 mL)⁐ᾮ࡟ 0 °C ࡛ NaBH4 (7.9

mg, 0.21 mmol)ࢆຍ࠼ࠊྠ ᗘ᮲௳࡛ 5 ศ㛫᧠ᢾࡋࡓࠋ཯ᛂ⤊஢ࢆ TLC (EtOAc/n-Hexane = 2/1)

࡛☜ㄆࡋࠊᕼ㔘ᚋ(EtOAc)ࠊὙί(⵨␃Ỉࠊ㣬࿴㣗ሷỈ)ࠊ஝⇱(↓Ỉ◲㓟ࢼࢺ࣒ࣜ࢘)ࠊ⁐፹␃

ཤࢆ⾜ࡗࡓࠋᚓࡽࢀࡓṧ´ࢆࢩࣜ࢝ࢤ࣒ࣝ࢝ࣛࢡ࣐ࣟࢺࢢࣛࣇ࢕࣮(EtOAc/n-Hexane = 3/1)

࡛⢭〇ࡋ໬ྜ≀33 (41 mg, 82%)ࢆ↓Ⰽ⢓ᛶᾮయ࡜ࡋ࡚ᚓࡓࠋ[α]D -43.7 ° (c 0.4, CHCl3); 1H

NMR (500 MHz, CDCl3), δ 4.98 (dd, 1 H, J3,4 = 3.5 Hz, J4,5 = 1.0 Hz, H-4), 4.87 (d, 1 H, J1,2 = 3.5

Hz, H-1), 4.81 (d, 1 H, Jgem = 12.0 Hz, OCH2OCH3), 4.74 (d, 1 H, Jgem = 12.0 Hz, OCH2OCH3),

4.35-4.30 (m, 2 H, H-3, H-5), 4.00 (m, 1 H, H-3), 3.84 (t, 1 H, J2,3 = 3.5 Hz, H-3), 3.68 (d, 1 H, J3, OH

= 8.0 Hz, OH), 3.47-3.43 (m, 6 H, 2 OCH3), 2.14 (s, 3 H, Ac), 1.16 (d, 3 H, J5,6 = 6.5 Hz, H-6); 13C

NMR (125 MHz, CDCl3) δ 170.0, 100.1, 95.9, 73.6, 71.0, 68.3, 60.5, 55.9, 55.7, 20.9, 15.7 ; HRMS

(ESI) m/z: found [M+Na]+ 287.1103, C11H20O7 calcd for [M+Na]+ 287.1101.

1,2-O-Diacetyl-6-deoxy-1,2-O-(1-methoxymethylidene)-α-L-galactopyranose (36)

࢔ࣝࢦࣥ㞺ᅖẼୗࠊࣇࢥ࣮ࢫ5 (5.00 g, 30.5 mmol)ࢆ pyridine-THF ࡟⁐ゎࡉࡏ 4-DMAP (37.0

(56)

53

ᛂ⤊஢ࢆTLC (MeOH/CHCl3 = 1/10)࡛☜ㄆᚋࠊ0 °C ࡛ MeOH ࢆຍ࠼཯ᛂࢆ೵Ṇࡉࡏࡓࠋࢺࣝ

࢚ࣥඹἛᚋࠊṧ´ࢆEtOAc ࡛ᕼ㔘ࡋࠊὙί(2M-ሷ㓟ࠊ⵨␃Ỉࠊ㣬࿴Ⅳ㓟Ỉ⣲ࢼࢺ࣒ࣜ࢘Ỉ

⁐ᾮࠊ㣬࿴㣗ሷỈ)ࠊ஝⇱(↓Ỉ◲㓟ࢼࢺ࣒ࣜ࢘)ࠊ⁐፹␃ཤࢆ⾜ࡗࡓࠋ24 ᫬㛫┿✵஝⇱ࡉࡏ

ࡓᚋࠊṧ´ࢆCH2Cl2 (20.0 mL)࡟⁐ゎࡉࡏࠊAc2O (23.0 mL, 244 mmol)࠾ࡼࡧ 25% HBr-HOAc

⁐ᾮ (40.0 mL)ࢆຍ࠼ 16 ᫬㛫᧠ᢾࡋࡓࠋ཯ᛂ⤊஢ࢆ TLC(EtOAc/n-Hexane = 1/5)࡛☜ㄆᚋࠊ

CH2Cl2 ࡛ᕼ㔘ࡋịᾎ࡬ὀ࠸ࡔࠋ཯ᛂ⁐ᾮࢆὙί(㣬࿴Ⅳ㓟ࢼࢺ࣒ࣜ࢘Ỉ⁐ᾮࠊ㣬࿴㣗ሷỈ)ࠊ

஝⇱(↓Ỉ◲㓟ࢼࢺ࣒ࣜ࢘)ࠊ⁐፹␃ཤᚋࠊ┿✵ࣛ࢖ࣥ࡟࡚ 12 ᫬㛫஝⇱ࡉࡏࡓࠋᚓࡽࢀࡓࣇ

ࢥࢩࣝࣈ࣑ࣟࢻࢆDCE (95.3 mL).࡟⁐ゎࡉࡏ triethylamine (8.50 mL, 61.0 mmol)ࠊMeOH (1.40

mL, 33.6 mmol)ࡑࡋ࡚ TBAB (4.93 g, 15.3 mmol)ࢆᐊ ࡛ຍ࠼ࠊ50 °C ࡛ 5 ᫬㛫᧠ᢾࡋࡓࠋ཯

ᛂ⤊஢ࢆTLC (EtOAc/n-Hexane = 1/3)࡛☜ㄆᚋࠊᅛᙧ≀ࢆࢁ㐣ࡋ CH2Cl2࡛Ὑίࡋࡓࠋࢁᾮࢆ

Ὑί(2M-ሷ㓟ࠊ⵨␃Ỉࠊ㣬࿴Ⅳ㓟ࢼࢺ࣒ࣜ࢘Ỉ⁐ᾮࠊ㣬࿴㣗ሷỈ), ஝⇱ (↓Ỉ◲㓟ࢼࢺࣜ࢘

࣒)ࠊ⁐፹␃ཤᚋࠊᚓࡽࢀࡓṧ´ࢆࢩࣜ࢝ࢤ࣒ࣝ࢝ࣛࢡ࣐ࣟࢺࢢࣛࣇ࢕࣮(EtOAc/n-Hexane =

1/5)࡛⢭〇ࡋ໬ྜ≀ 36 (8.65 g, 90%)ࢆ↓Ⰽ⢓ᛶᾮయ࡜ࡋ࡚ᚓࡓࠋ1H NMR (500 MHz, CDCl3) δ

5.80 (d, 1 H, J1,2 = 5.0 Hz, H-1), 5.27-5.25 (m, 1 H, H-4), 5.04 (dd, 1 H, J2,3 = 7.0 Hz, J3,4 = 3.0 Hz,

H-3), 4.29-4.23 (m, 2 H, H-2, H-5), 3.30 (s, 3 H, OCH3), 2.14 (s, 3 H, Ac), 2.06 (s, 3 H, Ac), 1.20 (d,

3 H, J5,6 = 6.5 Hz, H-6); HRMS (ESI) m/z: found [M+Na]+ 327.1050, C13H20O8 calcd for [M+Na]+

327.1045.

6-Deoxy-1,2-O-(1-methoxymethylidene)-α-L-galactopyranose (37)

໬ྜ≀ 36 (1.00 g, 3.28 mol)ࢆ MeOH (6.56 mL)࡟⁐ゎࡉࡏ Sodium methoxide (28% in MeOH,

21.0 mg, 400 μmol)ࢆຍ࠼ࠊᐊ ࡟࡚ 30 ศ㛫᧠ᢾࡋࡓࠋ཯ᛂ⤊஢ࢆ TLC (EtOAc/n-Hexane = 1/1)

(57)

54

ℐᾮࢆ⃰⦰ࡋࢩࣜ࢝ࢤࣝࢡ࣐ࣟࢺࢢࣛࣇ࢕࣮ (MeOH/CHCl3 = 1/20) ࡛⢭〇ࡋ໬ྜ≀ 37 (720

mg, 99%) ࢆⓑⰍಶయ࡜ࡋ࡚ᚓࡓࠋ1_{H NMR (500 MHz, CDCl}

3) δ 5.74 (d, 1 H, J1,2 = 5.0 Hz, H-1),

4.25 (t, 1 H, J2,3 = 5.0 Hz, H-2), 4.04-4.00 (m, 1 H, H-5), 3.88-3.85 (m, 1 H, H-3), 3.78-3.75 (m, 1 H,

H-4), 3.38 (m, 1 H, OH-3), 3.29 (s, 3 H, OCH3), 2.84 (s, 1 H, OH-4), 1.32 (d, 3 H, J5,6 = 6.5 Hz,

H-6); HRMS (ESI) m/z: found [M+Na]+ 243.0839, C9H16O6 calcd for [M+Na]+ 243.0842.

3,4-Di-O-benzyl-6-deoxy-L-galactopyranose (38) ࢔ࣝࢦࣥ㞺ᅖẼୗࠊ໬ྜ≀37 (700 mg, 3.17 mmol)ࢆ DMF (16.0 mL)࡟⁐ゎࡉࡏࠊ0 °C ࡛ NaH (1.20 g, 6.99 mmol)ࢆຍ࠼ 1 ᫬㛫᧠ᢾࡋࡓࠋྠ ᮲௳ୗ࡛ BnBr (834 μL, 6.99 mmol)ࢆຍ࠼ࡓ ᚋࠊᐊ ࡛24 ᫬㛫᧠ᢾࡋࡓࠋ཯ᛂ⤊஢ࢆ TLC (EtOAc/Toluene = 1/1)࡛☜ㄆᚋࠊ0 °C ࡛ MeOH ࢆຍ࠼཯ᛂࢆ೵Ṇࡉࡏࡓࠋ཯ᛂ⁐ᾮࢆEtOAc ࡛ᕼ㔘ᚋࠊ2M-ሷ㓟ࢆຍ࠼ 10 ศ㛫᧠ᢾࡋࡓࠋ ࢜ࣝࢯ࢚ࢫࢸࣝࡢຍỈศゎࢆTLC (EtOAc/Toluene = 1/1)࡛☜ㄆᚋࠊὙί(⵨␃Ỉࠊ㣬࿴Ⅳ㓟 Ỉ⣲ࢼࢺ࣒ࣜ࢘Ỉ⁐ᾮࠊ㣬࿴㣗ሷỈ)ࠊ஝⇱ (↓Ỉ◲㓟ࢼࢺ࣒ࣜ࢘)ࠊ⁐፹␃ཤࢆ⾜ࡗࡓࠋ3

᫬㛫┿✵஝⇱ࢆ⾜ࡗࡓṧ´ࢆࠊMeOH (6.30 mL) ࡟⁐ゎࡉࡏࠊsodium methoxide (28% in MeOH,

61.2 mg, 317 μmol)ࢆᐊ ࡛ຍ࠼ࠊ20 ศ㛫᧠ᢾࡋࡓࠋ཯ᛂ⤊஢ࢆ TLC (MeOH/CHCl3 = 1/10) ࡛☜ㄆᚋࠊMuromac (H+)࡟ࡼࡾ୰࿴ࡋࡓࠋᶞ⬡ࢆࢁ㐣ᚋࠊMeOH ࡛Ὑίࡋℐᾮࢆ⃰⦰ࡋࡓࠋ ᚓࡽࢀࡓṧ´ࢆࢩࣜ࢝ࢤ࣒ࣝ࢝ࣛࢡ࣐ࣟࢺࢢࣛࣇ࢕࣮ (MeOH/CHCl3 = 1/25)࡛⢭〇ࡋ໬ྜ ≀38 (911 mg, 83%)ࢆⓑⰍᅛయ࡜ࡋ࡚ᚓࡓࠋ1H NMR (500 MHz, CDCl3) δ 7.37-7.23 (m, 10 H, Ar), 5.31 (d, 1 H, J1,2 = 3.5 Hz, H-1), 4.93-4.63 (m, 4 H, 2 ArCH2), 4.15 (dd, 1 H, J2,3 = 9.5 Hz, H-2), 3.74 (dd, 1 H, J3,4 = 2.5 Hz, H-3), 3.68 (d, 1 H, J4,5 = 1.5 Hz, H-4), 3.53 (m, 1 H, H-5), 1.18 (d, 3 H,

J5,6 = 6.5 Hz, H-6); HRMS (ESI) m/z: found [M+Na]+ 367.1516, C20H24O5 calcd for [M+Na]+