抗ウイルス剤の創製を目指した新規炭素環ヌクレオシド類の合成 㩷

総  説㩷

抗ウイルス剤の創製を目指した新規炭素環ヌクレオシド類の合成 㩷

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ᾢᧄᶈ᮸㩷

ᤘ๺ᄢቇ⮎ቇㇱ⮎ຠ⵾ㅧൻቇᢎቶ㩷

㩷

ⷐ ᣦ㩷

᛫࠙ࠗ࡞ࠬ೷ߩഃ⵾ࠍ⋡ᜰߒߡᣂⷙ὇⚛Ⅳ࠿ࠢ࡟ࠝࠪ࠼ࠍ࠺ࠩࠗࡦߒ㧘ߘߩวᚑ⎇ⓥࠍⴕߞ ߚ㧚㪋㶅㪄ୃ㘼ဳ 㫅㪼㫇㫃㪸㫅㫆㪺㫀㫅㧭㩿㪋㪀ߩวᚑߦߪ࡜ࠫࠞ࡞෻ᔕࠍ೑↪ߔࠆ⣕⎫⊛ࠬ࠲࠾࡞ൻࠍ㧘㪋㶅㪄὇⚛

⟎឵㪙㪚㪘㩿㪌㪀ߩวᚑߦߪ㪪_㪟㶅ဳߩ࡜ࠫࠞ࡞㐽Ⅳ෻ᔕࠍߘࠇߙࠇ㎛Ბ㓏ߦㆡ↪ߔࠆߎߣߦࠃࠅ㧘ᮡ⊛

ൻว‛ࠍല₸⊛ߦวᚑߒߚ㧚߹ߚ㧘ࠫࡈࡠࡠ὇⚛Ⅳ 㪜㪻㪋㪫 ⺃ዉ૕㩿㪎㪀ߩวᚑߦ߅޿ߡߪ૏⟎ㆬᛯ⊛

ߥ࠴ࡒࡦႮၮߩዉ౉ߦߟ޿ߡᬌ⸛ߒߚ㧚㩷 㩷

㪢㪼㫐㩷㪮㫆㫉㪻㫊㧦὇⚛Ⅳ࠿ࠢ࡟ࠝࠪ࠼㧘ࡀࡊ࡜ࡁࠪࡦ㧭㧘㪋㶅㪄⟎឵࠿ࠢ࡟ࠝࠪ࠼㧘㪋㶅㧙ࠛ࠴࠾࡞㪻㪋㪫㩷

㩷

✜ ⸒

࠿ࠢ࡟ࠝࠪ࠼ߪ㧘㪛㪥㪘 ߿㪩㪥㪘ߩ᭴ᚑᚑಽߣߒߡ ߩᓎഀߩߺߥࠄߕ㧘㪘㪫㪧ߦઍ⴫ߐࠇࠆࠃ߁ߦࠛࡀ࡞

ࠡ࡯ઍ⻢ߦ㑐ਈߔࠆ߽ߩ߆ࠄ㧘㪬㪛㪧㪄㪞㫃㫌㪄㧺㪄㪘㪺ߩࠃ ߁ߦࡃࠢ࠹࡝ࠕ⚦⢩ოߩ↢วᚑߦ㑐ࠊࠆ߽ߩ߹ߢߘ ߩᯏ⢻ߪᄙ⒳ᄙ᭽ߢ޽ࠅ㧘ක⮎ຠࠍഃ⵾ߔࠆߚ߼ߩ

ᩰᅢߩࡕ࠴࡯ࡈߣ⠨߃ࠄࠇࠆ㧚੐ታ㧘੹ᣣ߹ߢߦว ᚑߐࠇߚᢙᄙߊߩୃ㘼࠿ࠢ࡟ࠝࠪ࠼ߩਛ߆ࠄ㧘᛫ᖡ ᕈ⣲≌⮎㧘᛫࠙ࠗ࡞ࠬ⮎㧘఺∉ᛥ೙⮎ߥߤߩක⮎ຠ

߇਎ߦㅍࠅ಴ߐࠇߡ߈ߚ㧚㩷

὇⚛Ⅳ࠿ࠢ࡟ࠝࠪ࠼ߣߪ㧘ᄤὼߦሽ࿷ߔࠆ࠿ࠢ࡟

ࠝࠪ࠼ߩࡈ࡜ࡁ࡯ࠬⅣౝ㉄⚛ේሶࠍࡔ࠴࡟ࡦ㧔㪚㪟_㪉㧕 ߢ⟎឵ߒߚ⺃ዉ૕ߩ✚⒓ߢ޽ࠅ㧘ࠕ࠮࠲࡯࡞᭴ㅧࠍ

᦭ߔࠆᄤὼဳ࠿ࠢ࡟ࠝࠪ࠼ߩൻቇ⊛߅ࠃ߮↢‛ቇ⊛

቟ቯ╬ଔ૕ߣߒߡ⣉శࠍᶎ߮ߡ޿ࠆ㧚ߎࠇࠄߩ὇⚛

Ⅳ ࠿ ࠢ ࡟ ࠝ ࠪ ࠼ ߩ ਛ ߦ ߪ 㪺㪸㫉㪹㫆㫍㫀㫉㩿㪈㪀^㪈㪀 ߿

㫅㪼㫇㫃㪸㫅㫆㪺㫀㫅㪘㩿㪉㪀^㪉㪀ߩࠃ߁ߦᒝജߥ᛫࠙ࠗ࡞ࠬ૞↪ࠍ␜

ߔ߽ߩ߇⷗಴ߐࠇߡ߅ࠅ㧘㪈ߩࡊࡠ࠼࡜࠶ࠣߢ޽ࠆ 㪸㪹㪸㪺㪸㫍㫀㫉㩿㪊㪀^㪊㪀ߪ⃻࿷᛫㪟㪠㪭೷ߣߒߡ⥃ᐥߩ⃻႐ߢ૶↪

ߐࠇߡ޿ࠆ㧔㪝㫀㪾㫌㫉㪼㩷㪈㧕㧚㩷

⪺⠪ࠄߪㄭᐕ㧘วᚑൻቇ⊛߅ࠃ߮ක⮎ຠൻቇ⊛ߥ

⥝๧߆ࠄ὇⚛Ⅳ࠿ࠢ࡟ࠝࠪ࠼ߩวᚑ⎇ⓥࠍ⛯ߌߡ߈ ߚ㧚ᧄⓂߢߪએਅߦ␜ߔᣂⷙ὇⚛Ⅳ࠿ࠢ࡟ࠝࠪ࠼㘃 㧔㪋㪄㪎㧕ߩวᚑߦߟ޿ߡ㗅ᰴ⚫੺ߐߖߡ޿ߚߛߊ㧚㩷

㩷

HO N

N

N N R

NH

1 R = OH (carbovir) 3 R = NHC3

H

(abacavir)

N N N

N NH

HO

OH HO

2 (neplanocin A)

N N N

N NH

R OH HO

N N N

N NH

OH HO

R

HO R

N NH O

O Me

HO NH

N O

O Me

F F

carbon-substituents

6 R = ethynyl, cyano 7 Figure 1. Structures of compounds 1-7.

1' 3' 2'

4' 5' 6'

4' 1'

2' 3' 4'5'

5'' 4''

1' 2' 3'

4' 1'

2' 3' 4' 5'

㩷

O S Me

O

C NH

2

HO OH

N N N

N NH

8 (AdoMet)

O S O

C

NH

2

HO OH

N N N

N NH

9 (AdoHcy)

NH N N

N O

NH

mRNA

NH N N

N O

NH

mRNA

Me methyltransferase

L -homocysteine + adenosine

SAHase

negative feedback

Scheme 1

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㧝㧚⣕⎫⊛ࠬ࠲࠾࡞ൻࠍ㎛෻ᔕߣߔࠆᣂⷙ㪋㶅㪄ୃ㘼

ဳ㫅㪼㫇㫃㪸㫅㫆㪺㫀㫅㧭ߩวᚑ^㪋㪀㩷

⌀ᩭ↢‛ߩ㫄㪩㪥㪘ߪߘߩᚑᾫㆊ⒟ߦ߅޿ߡ㧘㫄㪩㪥㪘

ࠠࡖ࠶ࡊㇱࠣࠕ࠾ࡦႮၮ㧺㪎૏߅ࠃ߮㪉⇟⋡ߩ࠿ࠢ࡟

ࠝ࠴࠼ߩ♧ㇱ㪉㶅૏᳓㉄ၮ߇ࡔ࠴࡞ൻࠍฃߌࠆ㧚㩷

㪪㪺㪿㪼㫄㪼㪈^㪌㪃㪍㪀ߦ␜ߔࠃ߁ߦ㧘↢૕ౝߦ߅ߌࠆࡔ࠴࡞

ൻߪਥߦࠕ࠺ࡁࠪ࡞ࡔ࠴ࠝ࠾ࡦ㧔㪏㪃㩷㪘㪻㫆㪤㪼㫋㧕ࠍࡔ࠴

࡞ଏਈ૕ߣߔࠆ⒳ޘߩ㉂⚛෻ᔕߦࠃߞߡⴕࠊࠇࠆ㧚 ߎߩ෻ᔕߢ೽↢ߔࠆ㧿㪄ࠕ࠺ࡁࠪ࡞㪄㪣㪄ࡎࡕࠪࠬ࠹ࠗ

ࡦ㧔㪐㪃㩷㪘㪻㫆㪟㪺㫐㧕ߪ㧘ࡔ࠴࡞ൻ㉂⚛ߦኻߔࠆࡈࠖ࡯࠼

ࡃ࠶ࠢ㒖ኂ೷^㪎㪀ߣߒߡ௛ߊ߇㧘㧿㪄ࠕ࠺ࡁࠪ࡞㪄㧸㪄ࡎ ࡕࠪࠬ࠹ࠗࡦട᳓ಽ⸃㉂⚛㧔㪪㪘㪟㪸㫊㪼㧕^㪎㪃㪏㪀ߦࠃߞߡㅦ

߿߆ߦઍ⻢ߐࠇࠆߎߣߢࡔ࠴࡞ൻߩᱜᏱߥ࡟ࡌ࡞ࠍ

⛽ᜬߒߡ޿ࠆ㧚㩷 㩷

N N N

N NH

Bu

Sn

OPg PgO

Bu

Sn

OPg PgO

OH PhS(O)

OPg PgO

OH

A

B C n = 0 or 2

4

Pg = protecting group

Scheme 2. Synthetic plan.

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ߎߩࠃ߁ߥⷰὐ߆ࠄ㧘࠙ࠗ࡞ࠬ↱᧪ߩ 㪪㪘㪟㪸㫊㪼 ࠍ

․⇣⊛ߦ㒖ኂߔࠆ‛⾰ߩ㐿⊒ߪ᛫࠙ࠗ࡞ࠬൻቇ≮ᴺ ߦ߅ߌࠆᣂߒ޿ᚢ⇛ߩ৻ߟߣߒߡᦼᓙߐࠇߡ޿ࠆ㧚

㪐㪃㪈㪇㪀࠿ࠢ࡟ࠝࠪ࠼♽᛫↢‛⾰ߢ޽ࠆࡀࡊ࡜ࡁࠪࡦ㧭

㧔㪝㫀㪾㫌㫉㪼㪈㧘㪉㧕^㪉㪀ߪ㪪㪘㪟㪸㫊㪼ߦኻߔࠆᒝജߥ㒖ኂ૞↪ࠍ

᦭ߔࠆ߇㧘หᤨߦᒝ޿⚦⢩Ქᕈࠍ␜ߔ㧚ᧄൻว‛ߩ

⚦⢩Ქᕈߪ㪍㶅૏৻⚖᳓㉄ၮߩ࡝ࡦ㉄ൻߦ⿠࿃ߔࠆ ߣ⠨߃ࠄࠇߡ߅ࠅ㧘Ქᕈߩシᷫࠍ⋡⊛ߣߒߡ⒳ޘߩ ൻቇᄌ឵߅ࠃ߮⺃ዉ૕ߩวᚑ߇ⴕࠊࠇߡ߈ߚ㧚^{㪈㪈㪄㪈㪋㧕} ߎߩࠃ߁ߥ⢛᥊߆ࠄ⪺⠪ࠄߪ㧘㪍㶅૏᳓㉄ၮࠍᰳߊᣂ ⷙ㪋㶅㪄ୃ㘼ဳࡀࡊ࡜ࡁࠪࡦ㧭⺃ዉ૕㩿㪋㪀ࠍ࠺ࠩࠗࡦߒ ߘߩวᚑߦ⌕ᚻߒߚ㧚㩷

ᮡ⊛ൻว‛ߩวᚑ⸘↹ࠍ 㪪㪺㪿㪼㫄㪼㩷 㪉ߦ␜ߔ㧚ฦ⒳

㪋㶅㪄ୃ㘼ဳ⺃ዉ૕㪋ߪ㧘ࡆ࠾࡞ࠬ࠲࠽ࡦ㧭ࠍ౒ㅢߩਛ 㑆૕ߣߔࠆߎߣߦࠃࠅวᚑߢ߈ࠆߣ⠨߃ߚ㧚วᚑਛ 㑆૕㧭ߪ㧘ࠕ࡝࡞ࠕ࡞ࠦ࡯࡞㧮ߦኻߔࠆ 㪪_㪥㪉⊛ߥࠕ

࠺࠾ࡦႮၮߩዉ౉ߦࠃࠅ⺞⵾ߔࠆߎߣߦߒߚ㧚߹ߚ㧘 㧮ߩࡆ࠾࡞ࠬ࠲࠽ࡦߩ᭴▽ߦߪ࡜ࠫࠞ࡞೨㚟૕㧯ߦ ኻߔࠆ⣕⎫⊛ࠬ࠲࠾࡞ൻ෻ᔕ^{㪈㪌㪄㪉㪍㧕}ࠍㆡ↪ߔࠆ⸘↹ࠍ

┙ߡߚ㧚㩷

࡜ࠫࠞ࡞೨㚟૕㧯ߩวᚑࠍ⹜ߺߚ㧔㪪㪺㪿㪼㫄㪼㩷㪊㧕㧚ኈ ᤃߦ౉ᚻน⢻ߥࡔ࠴࡞㪄ǩ㪄㧰㪄ࡑࡦࡁࡇ࡜ࡁࠪ࠼㧔㪈㪇㧕 ࠍ಴⊒ේᢱߣߒߡ↪޿㧘৻⚖㵨᳓㉄ၮߩ࡛࠙⚛ൻߣࠪ

ࠬࠫࠝ࡯࡞ߩࠕ࠮࠲࡯࡞ൻࠍ⚻ߡ㪈㪈ߣߒߚ㧚^㪉㪎㧕ᵴᕈ ൻ੝㋦ᧃࠍ↪޿ࠆ⣕㔌ߦࠃࠅ^㪉㪏㧕ࡋࡒࠕ࠮࠲࡯࡞㪈㪉^㪉㪐㧕 ߣߒߚᓟ㧘㪮㫀㫋㫋㫀㪾 ෻ᔕߦࠃࠅ㪈㪃㪍㪄ࠫࠛࡦ㪈㪊߳ᄌ឵ߒ

ߚ㧚㪞㫉㫌㪹㪹㫊╙৻਎ઍ⸅ᇦࠍ↪޿ࠆ㪈㪊ߩ㐽Ⅳࡔ࠲࠮ࠪ

ࠬߪല₸⊛ߦㅴⴕߒ㧘↢ᚑߒߚࠕ࡝࡞ࠕ࡞ࠦ࡯㩷_㩷

࡞ߩ 㪧㪛㪚 ㉄ൻࠍ⚻ߡࠪࠢࡠࡍࡦ࠹ࡁࡦ㪈㪋^{㪊㪇㪄㪊㪊㧕}ࠍᓧ ߚ㧚ൻว‛㪈㪋ߦኻߔࠆ࠴ࠝࡈࠚࡁ࡯࡞ߩ㪈㪃㪋㪄ઃട߅

ࠃ߮㪥㪚㪪ࠍ↪޿ࠆ㪧㫌㫄㫄㪼㫉㪼㫉ဳߩ㉄ൻ෻ᔕ^㪊㪋㧕ߦࠃࠅ

㪈㪍ߣߒߚᓟ㧘㪣㫌㪺㪿㪼ㆶర^㪊㪌㧕ߦࠃࠅࡆ࠾࡞ࠬ࡞ࡈࠖ࠼

㪈㪎ࠍ㧘߹ߚ⎫㤛ේሶߩ㨙㪄㪚㪧㪙㪘㉄ൻߦࠃߞߡࡆ࠾࡞

ࠬ࡞ࡎࡦ㪈㪏ࠍߘࠇߙࠇวᚑߒߚ㧚㩷

O O

OH

i, ii) iii)

v, vi)

10 11 12

Scheme 3. Preparation of 17 and 18. i) I

, Ph

P, imidazole, THF, reflux; ii) 2,2-dimethoxypropane, TsOH, acetone, rt, (93% from 10); iii) Zn powder, EtOH, H

O, 100

C, (93%); iv) Ph

PCH

Br, NaH, DMSO, THF, reflux; v) Grubbs

, CH

Cl

, rt; vi) PDC, CH

Cl

, (72% from 13); vii) PhSH, Et

N, CH

Cl

, rt, (81%); viii) NCS,CH

Cl

, rt, (94%); ix) NaBH

, CeCl

7H

O, NeOH, 40

C, (99%); x) m-CPBA, CH

Cl

, rt, (100%).

O O

O

14 O

O O

15 PhS

O O

O

16 PhS

O O PhS

OH

O O

O O HO

O O MeO

OH I MeO O

OH OH

HO HO

O O PhO

S

OH iv)

13 vii)

viii)

17 18

ix) x)

㩷

ൻว‛㪈㪎߅ࠃ߮㪈㪏ߩ࡜ࠫࠞ࡞෻ᔕߦࠃࠆ⣕⎫⊛ࠬ

࠲࠾࡞ൻߦߟ޿ߡᬌ⸛ߒߚ㧔㪫㪸㪹㫃㪼㩷㪈㧕㧚^{㪈㪌㪄㪉㪍㪀}ࡆ࠾࡞ࠬ

࡞ࡈࠖ࠼㪈㪎ࠍࡌࡦ࠯ࡦਛ㨕㪄㪧㫉_㪉㪥㪜㫋߅ࠃ߮㪉㪃㪉㶅㪄ࠕ࠱

ࡆࠬࠗ࠰ࡉ࠴ࡠ࠾࠻࡝࡞㧔㪘㪠㪙㪥㧕ሽ࿷ਅ࠻࡝ࡉ࠴࡞

࠴ࡦࡅ࠼࡝࠼㧔㪙㫌_㪊㪪㫅㪟㧕ߣ෻ᔕߐߖߚ߇㧘⋡⊛ߣߔ ࠆࠬ࠲࠾࡞૕㪈㪐ߩ෼₸ߪࠊߕ߆㪋㧑ߦߣߤ߹ߞߚ 㧔㪼㫅㫋㫉㫐㩷㪈㧕㧚৻ᣇ㧘ࡆ࠾࡞ࠬ࡞ࡎࡦ㪈㪏ࠍၮ⾰ߣߒߡ↪

޿ห᭽ߩ෻ᔕࠍⴕߞߚߣߎࠈ㧘㪈㪐ߩ෼₸߇㪌㪉㧑ߦᡷ ༀߐࠇߚ㧚߹ߚ㧘ࠕ࡝࡞ࠕ࡞ࠦ࡯࡞ࠍ㫋㪼㫉㫋㪄ࡉ࠴࡞ࠫ

ࡔ࠴࡞ࠪ࡝࡞㧔㪫㪙㪛㪤㪪㧕ၮߢ଻⼔ߒߚ㪉㪇ࠍၮ⾰ߣߒ ߡ↪޿ߚ႐วߦߪ㧘ኻᔕߔࠆࠬ࠲࠾࡞૕㪉㪈ߩ෼₸ߪ 㪎㪐㧑ߦ߹ߢะ਄ߒ㧘ᦨ⚳⊛ߦߪࡌࡦ࠱ࠗ࡞㧔㪙㫑㧕ၮ ߢ଻⼔ߒߚ㪉㪉ࠍ↪޿ࠆߎߣߢ㧘⋡⊛ߣߔࠆࠬ࠲࠾࡞

૕㪉㪊ࠍ㪐㪋㧑ߩ෼₸ߢวᚑߔࠆߎߣ߇ߢ߈ߚ㧚ᧄࠬ࠲

࠾࡞ൻ෻ᔕߦ߅޿ߡⷰኤߐࠇߚ෼₸ߩᄌേߣၮ⾰ߩ

᭴ㅧߣߩ㑐ㅪߦߟ޿ߡߪ㧘⃻࿷⎇ⓥਛߢ޽ࠆ㧚㩷 వߦᓧࠄࠇߚ㪉㪊ߩࡌࡦ࠱ࠗ࡞ၮࠍ㒰෰ߒߡ㪈㪐ߣߒ ߚᓟ㧘㪤㫀㫋㫊㫌㫅㫆㪹㫌 ෻ᔕ^㪊㪍㧕ߦࠃࠆࡊ࡝ࡦႮၮߩዉ౉ࠍ

⹜ߺߚ㧔㪪㪺㪿㪼㫄㪼㩷㪋㧕㧚᳞ᩭ⹜⮎ߣߒߡ㪍㪄ࠢࡠࡠࡊ࡝ࡦ ࠍ↪޿ߚߣߎࠈ㧘૏⟎ㆬᛯ⊛ߥ⟎឵෻ᔕ߇ㅴⴕߒ㧘 㪉㪋ࠍ⦟ᅢߥ෼₸ߢਈ߃ߚ㧚ࡔ࠲ࡁ࡯࡞ᕈࠕࡦࡕ࠾ࠕ

㧔㪥㪟_㪊㪆㪤㪼㪦㪟㧕ߦࠃࠆ㪉㪋ߩടࠕࡦࡕ࠾ࠕಽ⸃ߦࠃࠅ㧘ᮡ

⊛ൻว‛㪋ߩ౒ㅢวᚑਛ㑆૕ߢ޽ࠆ㪉㪌߳ᄌ឵ߒߚ㧚^{㪊㪎㪃㩷㪊㪏㧕}㩷

O O PhO

S

OR O

O Bu

Sn

OR

17 n = 0, R = H 18 n = 2, R = H 20 n = 2, R = TBDMS 22 n = 2, R = Bz

19 R = H 21 R = TBDMS 23 R = Bz Bu

SnH (3 equiv)

AIBN (0.5 equiv) i-Pr

NEt (3 equiv) benzene, reflux 4h

Table 1. Radical-mediated stannylation of 17-22

entry substrate yield (%) of stannane recovery (%) 1

2 3 4

17 18 20 22

4 (19) 52 (19) 79 (21)

94 (23)

94 (17) 32 (18) 21 (20)

6 (22)

a)

Calculated by

H NMR spectroscopy.

㩷

N N N

N X

O O

Bu

Sn 6-chloropurine

DIAD, PPh

19 THF

24 X = Cl (80%) 25 X = NH

(87%) NH

/MeOH

Scheme 4. Introduction of purine base to 19.

ൻว‛㪉㪌ߩ㪋㶅૏ࠬ࠲࠾࡞ၮߩᄌ឵ߦࠃࠆฦ⒳㪋㶅

ୃ㘼ဳࡀࡊ࡜ࡁࠪࡦ㧭ߩวᚑࠍ⹜ߺߚ㧔㪫㪸㪹㫃㪼㪉㧕㧚㪫㪟㪝 ਛ࡛࠙⚛ߣ෻ᔕߐߖߚߣߎࠈ㧘ቯ㊂⊛ߥ෼₸ߢ㪋㶅㪄

࡛࡯࠼૕㪉㪍ࠍਈ߃ߚ㧔㪼㫅㫋㫉㫐㪈㧕㧚ห᭽ߦ㪥㪙㪪߅ࠃ߮㪥㪚㪪 ࠍ↪޿ࠆࡂࡠࠥࡦൻߦࠃࠅਛ⒟ᐲߩ෼₸ߢ㪋㶅㪄ࡉࡠ ࡓ૕㪉㪎߅ࠃ߮ࠢࡠ࡞૕㪉㪏ࠍᓧߚ㧔㪼㫅㫋㫉㫀㪼㫊㪉㪸㫅㪻㪊㧕㧚ࡄ࡜

ࠫ࠙ࡓ⸅ᇦࠍ↪޿ࠆ࡛࡯࠼ࡌࡦ࠯ࡦߣߩ㪪㫋㫀㫃㫃㪼෻ᔕ^㪊㪐㧕 ࠍ ㆡ ↪ ߒ ߚ ߣ ߎ ࠈ㪋㶅㪄ࡈ ࠚ ࠾ ࡞ ૕㪉㪐߇ ᓧ ࠄ ࠇ ߚ 㧔㪼㫅㫋㫉㫐㪋㧕㧚߹ߚ㪋㶅㪄࡛࡯࠼૕㪉㪍ࠍၮ⾰ߣߔࠆ 㪪㫋㫀㫃㫃㪼 ෻ ᔕߦࠃࠅ㧘㪋㶅૏ߦࠛ࠴࠾࡞ၮࠍ᦭ߔࠆ㪊㪇߅ࠃ߮㪊㪈ࠍ ߘࠇߙࠇ㜞෼₸ߢวᚑߒߚ㧔㪼㫅㫋㫉㫀㪼㫊㩷㪌㪸㫅㪻㩷㪍㧕㧚߹ߚ㪉㪍 ߩࠪࠕࡁൻߦߟ޿ߡ⒳ޘߩ᧦ઙਅߢ⹜ߺߚ⚿ᨐ㧘 㪼㫅㫋㫉㫐㩷㪐ߦ␜ߔࠃ߁ߦ㪉ଔࡄ࡜ࠫ࠙ࡓ⸅ᇦሽ࿷ਅߢൻቇ

㊂⺰㊂ߩ࡛࠙ൻ㌃߅ࠃ߮࠻࡝ࡉ࠴࡞࠴ࡦࠪࠕ࠾࠼

㧔㪙㫌_㪊㪪㫅㪚㪥㧕ߣ෻ᔕߐߖࠆߎߣߢ㪋㶅㪄ࠪࠕࡁ૕㪊㪉ࠍ⦟

ᅢߥ෼₸ߢᓧࠆߎߣ߇ߢ߈ߚ㧚^㪋㪇㪀㩷

એ਄ㅀߴߚࠃ߁ߦ㧘⪺⠪ࠄߪᣂⷙ㪋㶅ୃ㘼ဳࡀࡊ࡜

ࡁࠪࡦ㧭ߩวᚑߦߟ޿ߡᬌ⸛ߒߚ㧚࡜ࠫࠞ࡞෻ᔕߦ ࠃࠆ⣕⎫⊛ࠬ࠲࠾࡞ൻࠍㆡ↪ߔࠆߎߣߦࠃࠅ㧘ࡂࡠ

ࠥࡦൻߩߺߥࠄߕ὇⚛㪄὇⚛⚿วᒻᚑ෻ᔕߦ߽᦭↪

ߥࡆ࠾࡞ࠬ࠲࠽ࡦ㪈㪐ࠍല₸⊛ߦ⺞⵾ߔࠆߎߣ߇ߢ߈ ߚ㧚߹ߚ㧘㪋㶅૏ߩࠬ࠲࠾࡞ၮߩᄌ឵ߦࠃࠅฦ⒳㪋㶅ୃ㩷

25 R = SnBu

26 R = I 27 R = Br 28 R = Cl 29 R = Ph 30 R = 31 R = 32 R = CN Table 2. Conversion of SnBu

group of 25

N N N

N NH

O O

R

entry substrate condition products (% yield by isolation) 1

2 3 4 5 6 7 8 9

25 25 25 25 26 26 26 26 26

I

/ THF, rt NBS / THF, rt NCS / THF, rt

PhI, (PPh

)

PdCl

, CuI / DMF, 120

C , Pd(PPh

)

, CuI / THF, rt , Pd(PPh

)

, CuI / THF, rt Bu

SnCN, Pd(PPh

)

, CuI / DMF, 120

C Bu

SnCN, Pd(PPh

)

/ dioxane, 90

C Bu

SnCN, (PPh

)

PdCl

, CuI / DMF, 120

C

Bu

SnC CH Bu

SnC CMe

26 (100) 27 (67) 28 (49) 29 (51) 30 (83) 31 (100) 32 (9), 25 (11) 32 (25), 25 (20) 32 (73) C CH

C CMe

4a R = I 4b R = Br 4c R = Cl 4d R = Ph 4e R = 4f R = 4g R = CN N

N N

N NH

HO OH

R C CH

C CMe

㩷 㩷

㘼ဳ⺃ዉ૕ߩวᚑߦᚑഞߒߚ㧚ᓧࠄࠇߚ㪉㪍㪄㪊㪉ࠍ⣕଻

⼔ߒߡ㪋㨍㪄㪋㨓ߣߒߚᓟ㧘᛫࠙ࠗ࡞ࠬᵴᕈߩࠬࠢ࡝࡯

࠾ࡦࠣߦଏߒߚ߇㗼⪺ߥᵴᕈࠍ␜ߔൻว‛ߪ⷗಴ߐ ࠇߥ߆ߞߚ㧚㩷

㩷

㧞㧚㩷㪪_㪟㶅ဳߩ࡜ࠫࠞ࡞㐽Ⅳ෻ᔕࠍ㎛Ბ㓏ߣߔࠆ㪋㶅㪄

὇⚛⟎឵ࡆࠬ㧔ࡅ࠼ࡠࠠࠪࡔ࠴࡞㧕ࠪࠢࡠࡍࡦ

࠹࠾࡞ࠕ࠺࠾ࡦ㧔㪙㪚㪘㧕ߩวᚑ^㪋㪈㧕㩷

ࠞ࡞ࡏࡆ࡞㧔㪈㪃㩷 㪝㫀㪾㫌㫉㪼㩷 㪈㧕^㪈㪀ߦᒝജߥ᛫㪟㪠㪭ᵴᕈ߇

⷗಴ߐࠇߚߩࠍᯏߦ㧘὇⚛Ⅳ࠿ࠢ࡟ࠝࠪ࠼㘃ߩวᚑ⎇

ⓥ߇⋓ࠎߦⴕࠊࠇߡ߈ߡ޿ࠆ㧚ࡆࠬ㧔ࡅ࠼ࡠࠠࠪࡔ࠴

࡞㧕ࠪࠢࡠࡍࡦ࠹࠾࡞ࠕ࠺࠾ࡦ㧔㪙㪚㪘㧘㩷 㪊㪊㪃㩷㪝㫀㪾㫌㫉㪼㩷㪉㪀^㪋㪉㪀 ߪ㧘㪢㪸㫋㪸㪾㫀㫉㫀ࠄߦࠃߞߡ࡜࠮ࡒ૕ߣߒߡวᚑߐࠇߚ᛫

㪟㪠㪭ᵴᕈൻว‛ߢ޽ࠆ㧚ᓟߩ⎇ⓥߦࠃࠅ㧔㧙㧕㪄૕ߩ ߺ߇ᒝ޿᛫࠙ࠗ࡞ࠬ૞↪ࠍ␜ߔߎߣ߇⷗಴ߐࠇ㧘^㪋㪊㧕

ઁߩࠣ࡞࡯ࡊߦࠃߞߡߘߩਇᢧวᚑ߽㆐ᚑߐࠇߡ޿

ࠆ㧚^{㪋㪋㪃㩷 㪋㪌㧕}ᧄൻว‛ߪ㧘᛫࠙ࠗ࡞ࠬ૞↪ࠍ␜ߔ὇⚛Ⅳ

ࠝࠠ࠮࠲ࡁࠪࡦ㧔㪚㪦㪯㪫㧘㪊㪋㧕^{㪋㪍㪃㩷㪋㪎㪀}ߣ㪈ߣߩࡂࠗࡉ࡝࠶

࠼ߣߒߡ࠺ࠩࠗࡦߐࠇߚ߽ߩߢ㧘ߘߩ࡙࠾࡯ࠢߥ᭴ㅧ ߪวᚑൻቇ⊛ߦ߽⥝๧޽ࠆ߽ߩߢ޽ࠆ߇㧘㪙㪚㪘 ⺃ዉ

૕ߩวᚑߦ㑐ߔࠆႎ๔଀ߪ⊝ήߢ޽ࠆ㧚㩷

৻ᣇ㧘ᄤὼߦሽ࿷ߔࠆ࠿ࠢ࡟ࠝࠪ࠼ߩ♧ㇱ㪋㶅૏ߦ

ࠛ࠴࠾࡞ၮ㧘ࠪࠕࡁၮߥߤߩ὇⚛ቭ⢻ၮࠍ᦭ߔࠆ⺃

ዉ૕㧔㪊㪌㪃㩷 㪊㪍㧕^{㪋㪏㪄㪌㪇㧕}߇㧘㪊㶅૏᳓㉄ၮࠍ᦭ߒߡ޿ߥ߇ ࠄᒝജߥ᛫ 㪟㪠㪭 ᵴᕈࠍ␜ߔߎߣ߇ႎ๔ߐࠇߡ޿ࠆ㧚 ߎࠇࠄߩ⍮⷗ࠍၮߦ⪺⠪ࠄߪ㧘࠿ࠢ࡟ࠝࠪ࠼ߩ㪋㶅૏ ߦ⋧ᒰߔࠆ૏⟎ߦ὇⚛ቭ⢻ၮࠍ᦭ߔࠆ㪙㪚㪘⺃ዉ૕㩷

㩷

N N N

N NH

HO

OH 34 (COXT) O Base

HO

HO R

N N N

N NH

HO

OH 33 (BCA)

35 Base = Thy, R = CN 36 Base = Cyt, R = ethynyl

4' 4' 1'

2' 3'

5'

Figure 2. Structures of compounds 33-36.

㧔㪌㧘㪝㫀㪾㫌㫉㪼㩷㪈㧕ࠍ࠺ࠩࠗࡦߒ㧘ߘߩวᚑߦ⌕ᚻߒߚ㧚㩷

ᮡ⊛ൻว‛㪌ߩㅒวᚑ⚻〝ࠍ 㪪㪺㪿㪼㫄㪼㩷 㪌ߦ␜ߔ㧚ᧄ ൻว‛ߩวᚑߦ߅޿ߡᦨ߽㊀ⷐߥὐߪ㧘ᓟߦ㪈㶅૏㧘 㪌㶅૏߅ࠃ߮㪋㶅૏ߣߥࠆㇱ૏ߩ┙૕ൻቇߩ೙ᓮߢ޽

ࠆ㧚ߎࠇࠍ㆐ᚑߔࠆߦߪ㧘ࡆࠪࠢࡠ㨇㪊㪅㪊㪅㪇㨉࡜ࠢ࠻

ࡦ㛽ᩰߩ᭴▽㧔㪠㪠㪠ߩวᚑ㧕߇ᔅⷐߢ޽ࠅ㧘ᣢ⍮ൻว

‛㪊㪎߆ࠄᄌ឵น⢻ߣᕁࠊࠇࠆ࡜ࠫࠞ࡞೨㚟૕ 㪠㪭 ߦ 㪪_㪟㶅ဳߩ࡜ࠫࠞ࡞㐽Ⅳ෻ᔕࠍㆡ↪ߔࠆߎߣࠍ⸘↹ߒ ߚ㧚߹ߚ㧘㪠㪠߳ߪࡆࠪࠢࡠ࡜ࠢ࠻ࡦ㪠㪠㪠ߩ㉄ൻߦࠃߞ ߡ㧘㧵߳ߪࠕ࡝࡞ࠕ࡞ࠦ࡯࡞ 㪠㪠ߦኻߔࠆ 㪪_㪥㪉⊛ߥࠕ

࠺࠾ࡦႮၮߩዉ౉ߦࠃߞߡ⺃ዉߢ߈ࠆߣ⠨߃ߚ㧚౒

ㅢߩਛ㑆૕ߢ޽ࠆ㧵ߩ࡜ࠢ࠻ࡦㇱಽࠍᄌ឵ߔࠆߎߣ ߦࠃࠅ㧘⋡⊛ߣߔࠆฦ⒳㪋㶅㪄⟎឵૕㪌ࠍวᚑߔࠆߎߣ ߇น⢻ߢ޽ࠆ㧚㩷

N N N

N NH

O O 5

PgO

O O

PgO

OH O

O PgO

O O PgO

SePh

S(O)

Ph OTBDPS

O MeO

C

I

II III

IV

conversion of the lactone function

radical 5-exo-trig cyclization

Scheme 5. Retrosynthesis of 5

37 Pg = protecting group

㩷 㩷

࡜ࠫࠞ࡞೨㚟૕㪠㪭ߩ⺞⵾ࠍ⹜ߺߚ㧔㪪㪺㪿㪼㫄㪼㩷 㪍㧕㧚

ࠪࠢࡠࡍࡦ࠹ࡁࡦ㪊㪎^㪌㪈㧕ߦኻߒߡ㪧㪿㪪㪟ࠍ㪈㪃㪋ઃടߐߖ 㪊㪏ߣߒߚᓟ㧘ࠤ࠻ࡦߩㆶర㧘↢ᚑߒߚੑ⚖ࠕ࡞ࠦ࡯

࡞ߩ࠻࡝ࡈ࡝࡞ൻ߅ࠃ߮㪛㪙㪥ߦࠃࠆǪ㪄⣕㔌ࠍ⚻ߡ ࠕ࡝࡞ࠬ࡞ࡈࠖ࠼㪊㪐߳⺃ዉߒߚ㧚ߐࠄߦࠛࠬ࠹࡞ߩ ߌࠎൻ߅ࠃ߮࠮࡟ࡁࡔ࠴࡞ൻ^㪌㪉㧕ࠍ⚻ߡ㪋㪈ࠍᓧߚ㧚߹

ߚ㪊㪐ࠍ㨙㪄㪚㪧㪙㪘 ㉄ൻߒߡࠕ࡝࡞ࠬ࡞ࡎࡦ㪋㪇ߣߒߚ ᓟ㧘ห᭽ߩᚻᴺߦࠃࠅ㪋㪉߳ᄌ឵ߒߚ㧚㩷

਄⸥ߩᣇᴺߢ⺞⵾ߒߚ㪉⒳ߩ࡜ࠫࠞ࡞೨㚟૕㧔㪋㪈㪃㩷

㪋㪉㧕ࠍ↪޿ߡ㧘㪪_㪟㶅ဳߩ࡜ࠫࠞ࡞㐽Ⅳ෻ᔕࠍⴕߞߚ

㧔㪪㪺㪿㪼㫄㪼㩷㪎㧕㧚ࠕ࡝࡞ࠬ࡞ࡈࠖ࠼㪋㪈ࠍ࠻࡞ࠛࡦਛ㪘㪠㪙㪥 ߅ࠃ߮㨕㪄㪧㫉_㪉㪥㪜㫋ߩሽ࿷ਅߦ㪙㫌_㪊㪪㫅㪟ߣടᾲㆶᵹߐߖ ߚߣߎࠈ㧘ᦼᓙߒߚ㪌㪄㪼㫏㫆㪄㫋㫉㫀㪾 ᭽ᑼߩ㐽Ⅳ෻ᔕߣᒁ ߈⛯ߊ࠴ࠗ࡞࡜ࠫࠞ࡞ߩ⣕㔌߇ㅴⴕߒ㧘⋡⊛ߣߔࠆ ࡆࠪࠢࡠ㨇㪊㪅㪊㪅㪇㨉࡜ࠢ࠻ࡦ㪋㪊ࠍ㪍㪈㧑ߩ෼₸ߢᓧࠆߎ ߣ߇ߢ߈ߚ㧚ߒ߆ߒߥ߇ࠄᧄ෻ᔕߦ߅޿ߡߪ㧘ㆶర

૕㪋㪋㧔㪌㧑㧕߅ࠃ߮㪋㪌㧔㪈㪏㧑㧕ߩ೽↢߇⹺߼ࠄࠇߚ㧚

৻ᣇ㧘ࠕ࡝࡞ࠬ࡞ࡎࡦ㪋㪉ࠍၮ⾰ߣߒߡ↪޿ห᭽ߩ෻

ᔕࠍⴕߞߚ႐วߦߪ㧘㪋㪊ߩ෼₸ߪ㪐㪋㧑ߦ߹ߢะ਄ߒ㧘 ㆶర૕ߩ೽↢ߪోߊ⹺߼ࠄࠇߥ߆ߞߚ㧚㩷

⪺⠪ࠄߪ਄⸥࡜ࠫࠞ࡞㐽Ⅳ෻ᔕߦ߅ߌࠆ⚿ᨐߩᏅ

⇣ߦߟ޿ߡ⠨ኤߔߴߊ㧘એਅߩࡕ࠺࡞ታ㛎ࠍⴕߞߚ㧚

࡜ࠫࠞ࡞⊒↢Ḯߢ޽ࠆ㪧㪿㪪㪼ၮࠍᰳߊ㪊㪐߅ࠃ߮㪋㪇ࠍ㧘 ߘࠇߙࠇవߣห᭽ߩ᧦ઙਅߢ࡜ࠫࠞ࡞෻ᔕߦઃߒߚ㩷

TBDPSO

MeO

C

S(O)

Ph TBDPSO S(O)

Ph

O O SePh

39 n = 0 40 n = 2

O OTBDPS

MeO

C

SPh

a b, c, d

f, g

e

42 n = 2 Scheme 6, Reagents and conditions; a) PhSH, Et₃

N, CH

Cl

, b) NaBH

, MeOH, c) Tf

O, pyridine, CH

Cl

, d) DBN, MeCN (87% from

Cl

(96%), f), KOH, MeOH, H

O , g) PhSeCH

Cl, NaI, i-Pr

NEt, DME (68% for 41, 81% for 42).

37

㩷 㩷

O O

OTBDPS

O O

OTBDPS OTBDPS

MeO

C

+ +

43 44

41 or 42

Scheme 7. Radical reaction of 41 and 42 Bu

SnH, AIBN

i-Pr

NEt toluene, reflux

45

㩿㪪㪺㪿㪼㫄㪼㩷㪏㪃㩷㪼㫈㪅㩷㪈㩷㪸㫅㪻㩷㪼㫈㪅㩷㪉㪀㧚ߘߩ⚿ᨐ㧘ࠕ࡝࡞ࠬ࡞ࡈ

ࠖ࠼㪊㪐ࠍၮ⾰ߣߒߚ႐วߦߪㆶర૕㪋㪌㧔㪈㪌㧑㧕߇↢

ᚑߒߚߩߦኻߒߡ㧘ࠬ࡞ࡎࡦ㪋㪇ߪᧂ෻ᔕߩ߹߹ቯ㊂

⊛ߦ࿁෼ߐࠇߚ㧚ߎߩ੐ታߪ㧘㪪㪺㪿㪼㫄㪼㩷 㪎ߩ෻ᔕߦ߅

޿ߡ߽㪋㪈ߩ㪧㪿㪪ၮߩ⋥ធ⊛ߥㆶర߇૬⊒ߒߡ޿ࠆߎ ߣࠍᒝߊ␜ໂߔࠆ߽ߩߢ޽ࠆ㧚㩷

ࠕ࡝࡞ࠬ࡞ࡈࠖ࠼㪊㪐߿㪋㪈ߢߪ㧘㐽Ⅳ෻ᔕߩㅴⴕߦ

઻޿ 㪧㪿㪪㪟 ߇↢ᚑߔࠆ㧚৻⥸⊛ߦ㪧㪿㪪㪟 ߪ὇⚛࡜ࠫ

ࠞ࡞ߦኻߔࠆᒝജߥ᳓⚛ଏਈḮߣߒߡ௛ߊߎߣ߇⍮

ࠄࠇߡ߅ࠅ㧘^{㪌㪊㪃㪌㪋㧕}ߎࠇ߇ㆶర૕೽↢ߩⷐ࿃ߩ৻ߟߢ

޽ࠆߎߣ߇⠨߃ࠄࠇࠆ㧚੐ታ㧘వߩࠕ࡝࡞ࠬ࡞ࡎࡦ

㪋㪉ߩ㐽Ⅳ෻ᔕߦ㪇㪅㪌ᒰ㊂ߩ㪧㪿㪪㪟ࠍ౒ሽߐߖߚߣߎࠈ㧘

㪋㪊ߩ෼₸߇㪎㪇㧑ߦૐਅߔࠆߣ౒ߦㆶర૕㪋㪇㧔㪊㪇㧑㧕 ߩ↢ᚑ߇⏕⹺ߐࠇߚ㧔㪼㫈㪅㪊㪀㧚㩷

ᓧࠄࠇߚࡆࠪࠢࡠ㨇㪊㪅㪊㪅㪇㨉࡜ࠢ࠻ࡦ㪋㪊ࠍࠕ࡝࡞ࠕ

࡞ࠦ࡯࡞߳ᄌ឵ߔߴߊ㧘߹ߕࠛࡐࠠࠪൻࠍ⹜ߺߚ 㧔㪪㪺㪿㪼㫄㪼㩷 㪐㧕㧚ൻว‛㪋㪊ࠍ㨙㪄㪚㪧㪙㪘㉄ൻߒߚߣߎࠈ㧘

ࠛࡐࠠࠪ࠼㪋㪍߇㪉㪅㪍㧦㪈ߩഀวߢ↢ᚑߒ㧘㪥㪦㪜ታ㛎ߩ

⚿ᨐ߆ࠄਥ↢ᚑ‛ߪ 㪼㫅㪻㫆㪄㪋㪍ߢ޽ࠆߎߣ߇ࠊ߆ߞߚ㧚 ࡈࠚ࠾࡞࠮࡟ࡁࠕ࠾ࠝࡦߣ 㪼㫅㪻㫆㪄㪋㪍ߣߩ෻ᔕߪ㧘 㪍㪄㪧㪿㪪㪼૕㪋㪎㧔㪌㪎㧑㧕ߣ㪎㪄㪧㪿㪪㪼૕㪋㪏㧔㪊㪇㧑㧕ࠍਈ߃㩷

Bu

SnH, AIBN i-Pr

NEt, PhSH toluene, reflux

42 43 (70%) + 40 (30%)

39

Bu

SnH, AIBN i-Pr

NEt

toluene, reflux 45 (15%)

Scheme 8. Radical reaction of 39, 40 and 15 40

Bu

SnH, AIBN i-Pr

NEt

toluene, reflux 40 (100%)

eq. 1)

eq. 2)

eq. 3)

㩷 㩷

ߚ㧚৻ᣇ㧘೽↢ᚑ‛ߢ޽ࠆ㪼㫏㫆㪄㪋㪍ߣࡈࠚ࠾࡞࠮࡟ࡁ ࠕ࠾ࠝࡦߣߩ෻ᔕߢߪ㪎㪄㪧㪿㪪㪼 ૕㪋㪐ߩߺ߇㜞෼₸ߢ ᓧࠄࠇߚ㧚㩷

⋡⊛ߣߔࠆࠕ࡝࡞ࠕ࡞ࠦ࡯࡞߳ߩᄌ឵㧔࠮࡟ࡦේ

ሶߩ㉄ൻߣᒁ߈⛯ߊ㫊㫐㫅⣕㔌㧕ࠍ⠨ᘦߔࠆߣ㧘㪋㪐ߩ ߺࠍਈ߃ࠆ 㪼㫏㫆㪄㪋㪍ࠍ┙૕ㆬᛯ⊛ߦᓧࠆᔅⷐ߇޽ࠆ㧚

⒳ޘߩ෻ᔕ᧦ઙࠍᬌ⸛ߒߚ⚿ᨐ㧘㪋㪊ߦኻߒߡ㪥㪠㪪ߣ

㈶㉄ࠍ↪޿ࠆ࡛࡯࠼ࠕ࠮࠻ࠠࠪൻࠍⴕ޿ᒁ߈⛯߈Ⴎ ၮߢಣℂߔࠆߎߣߦࠃߞߡ㧘㪼㫏㫆㪄㪋㪍ࠍ⚂㪏㪇㧑ߩ෼₸

ߢᓧࠆߎߣ߇ߢ߈ߚ㧚㩷

਄ㅀߒߚ㨙㪄㪚㪧㪙㪘߅ࠃ߮㪥㪠㪪ߣ㪋㪊ߣߩ෻ᔕߢߪ㧘

޿ ߕ ࠇߩ ᳞㔚 ሶ ⹜⮎ ߽┙ ૕ ⊛ߦ ᷙߺ ว ߞߡ ޿ࠆ

㪺㫆㫅㪺㪸㫍㪼 㕙߆ࠄㆬᛯ⊛ߦੑ㊀⚿วߦធㄭߒߡ޿ࠆߎ

ߣߦߥࠆ߇㧘ߎߩℂ↱ߪ⃻Ბ㓏ߢ߽᣿ࠄ߆ߢߪߥ޿㧚

㪌㪌㪃㩷㪌㪍㧕㩷

ൻว‛㪋㪐ߩ㨙㪄㪚㪧㪙㪘㉄ൻ㧘࠮࡟ࡁࠠࠪ࠼ߩ㫊㫐㫅⣕ 㔌㧘ᦝߦ↢ᚑߒߚੑ⚖᳓㉄ၮߩ㪤㫀㫋㫊㫌㫅㫆㪹㫌෻ォࠍ⚻

ߡ㧘ࠕ࡝࡞ࠕ࡞ࠦ࡯࡞㪌㪈߳ᄌ឵ߒߚ㧔㪪㪺㪿㪼㫄㪼㪈㪇㧕㧚㩷

ᰴߦ㪌㪈ߦ㪤㫀㫋㫊㫌㫅㫆㪹㫌෻ᔕࠍㆡ↪ߒ㧘ࡊ࡝ࡦႮၮߩ ዉ౉ࠍ⹜ߺߚ㧚Ᏹᴺߦᓥ޿㧘㪍㪄ࠢࡠࡠࡊ࡝ࡦࠍ᳞ᩭ

⹜⮎ߣߒߡ↪޿ߚߣߎࠈ㧘⋡⊛ߣߔࠆ㧺㪐⟎឵૕㪌㪉 ߩ߶߆ߦ૏⟎⇣ᕈ૕ߢ޽ࠆ㪌㪊ߩ೽↢߇⹺߼ࠄࠇߚ㧚㩷

߹ߚ㧘㪌㪉ߩടࠕࡦࡕ࠾ࠕಽ⸃ߩⴕ⒟ߢߪ㧘⋡⊛‛

㪌㪋ߣ౒ߦ࡜ࠢ࠻ࡦߩ㐿Ⅳߦࠃࠆࠕࡒ࠼㪌㪌߇↢ᚑߒߡ ߈ߚ㧚ߎࠇࠄߩ໧㗴ߪ㧘ࡆࠬ㧔㫋㪼㫉㫋㪄ࡉ࠻ࠠࠪࠞ࡞ࡏ

࠾࡞㧕ࠕ࠺࠾ࡦ㪌㪍^{㪌㪎㪃㩷㪌㪏㧕}ࠍ↪޿ࠆߎߣߦࠃߞߡ⸃᳿ߢ ߈㧘㉄ᕈ᧦ઙਅߢߩ⣕㪙㫆㪺ൻߩᓟߦ㪌㪋ࠍ㪏㪊㧑ߩ෼₸

ߢᓧࠆߎߣ߇ߢ߈ߚ㧚ᧄൻว‛ߦ߅ߌࠆฦ⟎឵ၮߩ

⋧ኻ┙૕㈩⟎ߪ㨄✢⚿᥏᭴ㅧ⸃ᨆߦࠃߞߡ᳿ቯߒߚ 㧔㪝㫀㪾㫌㫉㪼㩷㪊㧕㧚㩷

ൻว‛㪌㪋ߩ 㪛㪠㪙㪘㪣㪄㧴ㆶరߦࠃߞߡᓧࠄࠇࠆࡋࡒ ࠕ࠮࠲࡯࡞㪌㪎ࠍ౒ㅢߩਛ㑆૕ߣߒߡ↪޿㧘ฦ⒳㪋㶅㪄

⟎឵૕ߩวᚑࠍⴕߞߚ㧔㪪㪺㪿㪼㫄㪼㪈㪈㧕㧚ࡋࡒࠕ࠮࠲࡯㩷

43

O O

OTBDPS

endo-46 O

O O

OTBDPS + O

O O

OTBDPS

49 (86%) OH SePh

O O

OTBDPS

47 (57%) SePh OH

O O

OTBDPS

48 (30%) OH SePh

+

Scheme 9, Reagents and conditions; a) method A: m- CPBA, CH

Cl

(69%, endo : exo = 2.6:1), method B: NIS, AcOH,CH

Cl

then NaOMe, MeOH (90%, endo : exo = 1:7), b) (PhSe)

, NaBH

, EtOH, rt

a

b b

exo-46

㩷

࡞㪌㪎ࠍ 㪥㪸㪙㪟_㪋ߢㆶరߔࠆߎߣߢ㪋㶅㪄ࡅ࠼ࡠࠠࠪࡔ࠴

࡞૕㪌㪏ࠍᓧߚ㧚ࡔ࠴࡟ࡦࡎࠬࡎ࡜ࡦࠍ↪޿ࠆ㪌㪎ߩ

㪮㫀㫋㫋㫀㪾෻ᔕߢߪ㪋㶅㪄ࡆ࠾࡞૕㪌㪐ࠍቯ㊂⊛ߦᓧߚ߇㧘቟

ቯࠗ࡝࠼ߣߩ෻ᔕߢߪ㪮㫀㫋㫋㫀㪾෻ᔕߦᒁ߈⛯߈ಽሶౝ

ߢߩ᳞ᩭ⊛㪈㪃㪋㪄ઃട߇ㅴⴕߒ㧘ࡆࠪࠢࡠൻว‛㪍㪇ࠍ ਈ߃ߚ㧚߹ߚ㧘ࠝࠠࠪࡓൻ㧘ࠕ࠮࠴࡞ൻ߅ࠃ߮㉄ᕈ

᧦ઙਅߢߩ⣕㔌ࠍ⚻ߡ㪋㶅㪄ࠪࠕࡁ૕㪍㪈߳ᄌ឵ߒߚ㧚

ࠛ࠴࠾࡞૕㪍㪉ߩวᚑߦ㑐ߒߡߪ⒳ޘߩ෻ᔕ᧦ઙߢᬌ

⸛ߒߚ߇㧘㪣㪛㪘 ߦࠃߞߡ⸃㔌ߐߖߚ 㪫㪤㪪 ࠫࠕ࠱ࡔ

࠲ࡦ^㪌㪐㧕ࠍ㪌㪎ߣ෻ᔕߐߖࠆߎߣߢ㧘ૐ෼₸ߢߪ޽ࠆ߇

⋡⊛ߣߔࠆ㪋㶅㪄ࠛ࠴࠾࡞૕㪍㪉ࠍᓧࠆߎߣ߇ߢ߈ߚ㧚㩷 એ਄ㅀߴߚࠃ߁ߦ㧘ᣂⷙ㪋㶅㪄὇⚛⟎឵㪙㪚㪘ߩวᚑ ߦߟ޿ߡᬌ⸛ߒߚ㧚ၮᧄ㛽ᩰߣߥࠆࡆࠪࠢࡠ㨇㪊㪅㪊㪅㪇㨉

࡜ࠢ࠻ࡦߪ㧘ࠕ࡝࡞ࠬ࡞ࡎࡦ㪋㪉ࠍၮ⾰ߣߔࠆ 㪪_㪟㶅ဳ ߩ࡜ࠫࠞ࡞㐽Ⅳ෻ᔕߦࠃࠅല₸⊛ߦ⺞⵾ߔࠆߎߣ߇ ߢ߈ߚ㧚ࡆࠪࠢࡠ࡜ࠢ࠻ࡦ㪋㪊ߩ㕙ㆬᛯ⊛ߥࠛࡐࠠࠪ

ൻߪ㧘࡛࡯࠼ࠕ࠮࠻ࠠࠪൻߣᒁ߈⛯ߊႮၮಣℂߦࠃ ࠅ㆐ᚑߒߚ㧚ࡊ࡝ࡦႮၮߩዉ౉ߪ㧘ࡆࠬ㧔㪙㫆㪺㧕ࠕ

࠺࠾ࡦࠍ↪޿ࠆ 㪤㫀㫋㫊㫌㫅㫆㪹㫌෻ᔕߦࠃߞߡ૏⟎߅ࠃ߮

┙૕ㆬᛯ⊛ߦⴕ߁ߎߣ߇ߢ߈ߚ㧚⣕ࠪ࡝࡞ൻߦࠃࠅ ᓧࠄࠇߚ㪌㪸㪄㪌㪺ߩ᛫㪟㪠㪭߅ࠃ߮᛫㪟㪚㪭ᵴᕈࠍ᷹ቯߒ ߚ߇㧘㗼⪺ߥ᛫࠙ࠗ࡞ࠬ૞↪ࠍ␜ߔ߽ߩߪ⷗಴ߐࠇ ߥ߆ߞߚ㧚㩷

49

O O

OTBDPS

R² 50: R¹ = OH, R² = H 51: R¹ = H, R² = OH R¹

O O

TBDPSO N

N N N

Cl

O O TBDPSO

N N N

N

Cl +

O O

TBDPSO N

N N N

NH₂

TBDPSO N

N N N

NH2

OH O

NH₂ +

52 53

54 55

a

b, c

d

e

f, g

Scheme 10, Reagents and conditions; a)m-CPBA, CH₂Cl₂then Et₃N, CH₂Cl₂, reflux (90%), b) AcOH, DEAD, Ph₃P, THF, 0^oC, c) K₂CO₃, MeOH, rt (98% from49), d) 6-chloropurine, DIAD, Ph₃P, THF,40^oC to rt, e) NH₃/MeOH, 120

oC in a seald tube, 54 (68% from 51) and 55 (5% from 51), f) 56, DIAD, Ph₃P, THF, 40 ^oC to rt, g) aq. 50% HCO₂H, THF, 50 ^oC, 54 (83% from 51)

N N N H N

N(Boc)2

56

㩷 㩷

㩷

Figure 3. ORTEP drawing of compound 54.

O HO

OPg Ade

57

O

OPg Ade

60

OPg Ade

58 OH HO

OPg Ade

OH MeO₂C

54

Scheme 11, Reagents and conditions; a) i-Bu₂AlH, CH₂Cl₂,78 ^oC (98%), b) NaBH₄, MeOH (86%), c) Ph₃PCH₃Br, BuLi, THF, 78 ^oC to rt (96%), d) Ph₃P=CHCO₂Me, xylene, reflux (72%), e) NH₂OH^.HCl, pyridine, f) Ac₂O, i-Pr₂NEt, MeCN, g) NaOAc, AcOH, 100

oC (84% from57), h) TMSCHN₂, LDA, THF,78^oC to rt (31%)

a

Ade = adenin-9-yl, Pg = TBDPS

OPg Ade

62 OH

OPg Ade

61 NC

OAc

b c d

e, f, g h

59

㩷

5a R = CH₂OH 5b R = CH=CH₂ 5c R = C CH OH

OH

R

Figure 4, Structures of 5a-5c

Ṓ

N N N

N NH₂

㩷

㩷

㧟㧚᛫㪟㪠㪭ᵴᕈൻว‛㪜㪻㪋㨀ߩ὇⚛Ⅳࠕ࠽ࡠࠣߩว ᚑ^{㪌㪈㪃㩷㪍㪇㪀㩷}

೨▵ߢㅀߴߚࠃ߁ߦ㧘♧ㇱ㪋㶅㪄⟎឵࠿ࠢ࡟ࠝࠪ࠼

㘃߇ᒝജߥ᛫㪟㪠㪭૞↪ࠍ␜ߔߎߣ߇ႎ๔ߐࠇߡએ᧪㧘 ߘࠇࠄߩ᭴ㅧᵴᕈ⋧㑐ߦ㑐ߔࠆᬌ⸛߇♖ജ⊛ߦⴕࠊ ࠇߡ߈ߡ޿ࠆ㧚^{㪋㪏㪄㪌㪇㧕}ᒰ⎇ⓥቶߩ㪟㪸㫉㪸㪾㫌㪺㪿㫀ࠄߪ㧘ࠛ

ࠗ࠭ᴦ≮⮎ߢ޽ࠆࠬ࠲ࡉࠫࡦ㧔㪍㪊㪃㪻㪋㪫㪃㩷㪝㫀㪾㫌㫉㪼㩷㪌㧕ߩ

♧ㇱ㪋㶅૏ߦࠛ࠴࠾࡞ၮࠍ᦭ߔࠆ⺃ዉ૕㪍㪋㧔㪜㪻㪋㨀㧕 ࠍวᚑߒ㧘ߎߩൻว‛߇Უൻว‛ߢ޽ࠆ㪍㪊ࠃࠅ߽ᒝ

޿᛫㪟㪠㪭૞↪ࠍ␜ߒ߆ߟૐᲥᕈߢ޽ࠆߎߣࠍ⷗಴ߒ

ߚ㧚^{㪍㪈㪄㪍㪋㧕}ᧄൻว‛ߪᄙ೷⠴ᕈࠍ₪ᓧߒߚᄌ⇣ᩣߦኻ

ߒߡ߽᦭ലߢ޽ࠆߎߣ߆ࠄ㧘ᣂⷙࠛࠗ࠭ᴦ≮⮎ߣߒ ߡ᦭ᦸⷞߐࠇߡ޿ࠆ㧚^㪍㪊㧕㩷

⪺⠪ࠄߪ 㪜㪻㪋㪫 ߩ᭴ㅧᵴᕈ⋧㑐ߦߟ޿ߡ⎇ⓥࠍ⛯

ߌߡ߈ߚ㧚วᚑᴺߩ⹦⚦ߦߟ޿ߡߪഀᗲߐߖߡ޿ߚ ߛߊ߇㧘ߎࠇ߹ߢߦ㪋㶅㪄࠴ࠝ⺃ዉ૕㪍㪌^㪍㪌㧕߅ࠃ߮὇⚛

Ⅳ⺃ዉ૕㪍㧔㧾㧩㪼㫋㪿㫐㫅㫐㫃㧘㪝㫀㪾㫌㫉㪼㩷㪈㧕^㪌㪈㧕ߩวᚑࠍႎ๔ ߒߚ㧚ߒ߆ߒߥ߇ࠄ㧘⃻Ბ㓏ߦ߅޿ߡ㪍㪋ߦൎࠆ᛫㪟㪠㪭

૞↪ࠍ␜ߔ߽ߩߪ⷗಴ߐࠇߡ޿ߥ޿㧚⪺⠪ࠄߪߎߩ

⎇ⓥߩ৻Ⅳߣߒߡ㧘὇⚛Ⅳ਄ߦ㪉ߟߩࡈ࠶⚛ේሶࠍ᦭

ߔࠆ⺃ዉ૕㪎㧔㪝㫀㪾㫌㫉㪼㩷㪈㧕ࠍ࠺ࠩࠗࡦߒߚ㧚ߔߥࠊߜ㧘 ࡈ࡜ࡁ࡯ࠬⅣౝ㉄⚛ේሶࠍࠛ࡯࠹࡞߹ߚߪࠛࠬ࠹࡞

㉄⚛ේሶߩ╬ଔ૕㧔㫀㫊㫆㫊㫋㪼㫉㪼㧕ߣߒߡ᳢↪ߐࠇߡ޿ࠆ

ࠫࡈࡠࡠࡔ࠴࡝࠺ࡦၮߢ⟎឵ߔࠆߎߣߢ㧘^{㪍㪍㪄㪎㪊㧕}㪍㪋ߩ ࡒࡒ࠶ࠢߣߒߡᯏ⢻ߔࠆߎߣࠍᦼᓙߒߚ߽ߩߢ޽ࠆ㧚㩷

㩷

O N

NH HO

R Me O

O S N

NH HO

Me O

O

63 R = H (d4T) 64 R = ethynyl (Ed4T)

65

Figure 5. Structures of compounds 63-65. 㩷 㩷

ࠫ ࡈ ࡠ ࡠ ὇ ⚛ Ⅳ ࡙ ࠾ ࠶ ࠻㪍㪍ߩ ว ᚑ ࠍ ⴕ ߞ ߚ 㧔㪪㪺㪿㪼㫄㪼㪈㪉㧕㧚ᣢ⍮ൻว‛ߢ޽ࠆࠕ࡝࡞ࠕ࡞ࠦ࡯࡞

㪍㪎^㪌㪈㧕ࠍ 㪧㪛㪚 ㉄ൻߒ㧘ࠤ࠻ࡦ㪍㪏ߣߒߚ㧚ൻว‛㪍㪏ࠍ

ࠪ࡝࡞ࠛࡁ࡯࡞ࠛ࡯࠹࡞ߣߒߚᓟ㧘㪪㪼㫃㪼㪺㫋㪽㫃㫌㫆㫉^տ㪎㪋㧕ࠍ

↪޿ࠆ᳞㔚ሶ⊛ࡈ࠶⚛ൻߦࠃࠅࡕࡁࡈࡠࡠ૕㪍㪐߳ᄌ

឵ߒߚ㧚ࡕࡁࡈࡠࡠ૕㪍㪐ߦኻߒߡౣᐲᧄ෻ᔕࠍㆡ↪

ߔࠆߎߣߦࠃࠅࠫࡈࡠࡠ૕㪎㪇ࠍ⦟ᅢߥ෼₸ߢᓧߚ㧚 ࠤ࠻ࡦ㪎㪇ߩ㪣㫌㪺㪿㪼ㆶరߪ┙૕ㆬᛯ⊛ߦㅴⴕߒ㧘ࠕ࡝

࡞ࠕ࡞ࠦ࡯࡞㪎㪈ࠍන৻ߩࠫࠕࠬ࠹࡟ࠝࡑ࡯ߣߒߡਈ ߃ߚ㧚ൻว‛㪎㪈ߩࡔ࠴࡞ࠛࠬ࠹࡞ࠍ 㪛㪠㪙㪘㪣㪄㧴ㆶర ߦࠃࠅࠕ࡞࠺ࡅ࠼ߣߒߚᓟ㧘㪦㪿㫀㫉㪸㪄㪙㪼㫊㫋㫄㪸㫅⹜⮎㧔㪎㪉㧕

㪎㪌㧕ߣ෻ᔕߐߖࠆߎߣߢ὇⚛Ⅳ࡙࠾࠶࠻㪍㪍߳⺃ዉߒߚ㧚㩷 㩷

OH MeO

C

PgO

O MeO

C

PgO

O MeO

C

PgO F

O MeO

C

PgO F F

OH MeO

C

PgO F F

OH

PgO F F

66

67 68

69 70

71

a b

c d

e

Pg = tert-butyldiphenylsilyl (TBDPS)

Scheme 12. Reagents and conditions: (a) PDC, CH₂

CH

(78%); (b) i) TMSCl, Li-HMDS, THF,

C; ii) Selectfluor, MeCN; (c) i) TMSCl, Li-HMDS, THF,

C, ii) Selectfluor, MeCN (76% from

, CeCl

7H

O, MeOH, THF,

C, (quant); (e) i) DIBAL-H, CH

CH

,

C; ii) P(O)(OMe)

C(N

)COMe (72),

K

CO

, MeOH (81% from 71).

㩷

㪤㫀㫋㫊㫌㫅㫆㪹㫌 ෻ᔕ^㪊㪍㧕ߦࠃࠆ࠴ࡒࡦႮၮߩዉ౉ࠍ⹜ߺ

ߚ㧔㪪㪺㪿㪼㫄㪼㪈㪊㧕㧚Ᏹᴺߦᓥ޿㪍㪍ߦኻߒ㪛㪠㪘㪛㧘㪧㪧㪿_㪊ሽ

࿷ਅ㧺^㪊㪄ࡌࡦ࠱ࠗ࡞࠴ࡒࡦߣ෻ᔕߐߖߚ㧚⣕ࡌࡦ࠱

ࠗ࡞ൻߩᓟන㔌♖⵾ࠍⴕߞߚߣߎࠈ㧘㪊⒳ߩ࠿ࠢ࡟ࠝ

ࠪ࠼⺃ዉ૕߇ᓧࠄࠇߚ㧚㪟㪤㪙㪚 ߅ࠃ߮ 㪥㪦㪜ታ㛎ߩ

⚿ᨐ߆ࠄਥ↢ᚑ‛ߪ㪪_㪥㪉㶅ᚑ❣૕㧔㪎㪊㪃㩷㪋㪈㧑㧘ǩ㪆Ǫ㧩

㪈㧦㪈㧕ߢ޽ࠆߎߣ߇್᣿ߒ㧘⋡⊛‛ߢ޽ࠆ 㪪_㪥㪉ᚑ❣

૕㪎㪋ߪࠊߕ߆ߦ㪉㪍㧑ߩ෼₸ߢᓧࠄࠇࠆߦㆊ߉ߥ߆ߞ ߚ㧚㩷

㪢㫆㫅㫅㫆ࠄ㧘^{㪎㪍㪄㪏㪇㧕}㪦㫂㪸㫅㫆ࠄ^㪏㪈㧕߅ࠃ߮㪢㫀㫄ࠄ^㪎㪊㧕ߪ㧘ߘ ࠇߙࠇ฽ࡈ࠶⚛ࠕ࡝࡞ࠕ࡞ࠦ࡯࡞ߦኻߔࠆ᳞ᩭ⟎឵

෻ᔕߦߟ޿ߡႎ๔ߒߡ޿ࠆ㧚޿ߕࠇߩႎ๔ߢ߽㧘᳞

ᩭ⹜⮎ߪ߽ߞ߬ࠄࡈ࠶⚛ේሶߩ㆙㓒૏ߦ⋧ᒰߔࠆ὇

⚛ේሶࠍ᡹᠄ߒߡ߅ࠅ㧘ߎߩ㈩ะᕈߪࡈ࠶⚛ේሶߩ 㔚ሶ⊛ലᨐߦ⿠࿃ߔࠆߣߐࠇߡ޿ࠆ㧚⪺⠪ࠄߪ㧘෻

ᔕὐߦ㓞ធߔࠆ⟎឵ၮߩ┙૕㓚ኂߦࠃߞߡ 㪪_㪥㪉㶅෻ ᔕߩ૬⊒ࠍ೙ᓮߢ߈ߥ޿߆ߣ⠨߃㧘એਅߩታ㛎ࠍⴕ ߞߚ㧔㪪㪺㪿㪼㫄㪼㪈㪋㧕㧚㪪_㪥㪉㶅෻ᔕὐߩ㓞ធ૏㧔ᓟߦ㪋㶅૏ ߣߥࠆ૏⟎㧕ߦᲧセ⊛߆ߐ㜞޿ 㪫㪙㪛㪧㪪㪦㪚㪟_㪉ၮࠍዉ

౉ߒߚ㪎㪌ࠍ⺞⵾ߒ 㪤㫀㫋㫊㫌㫅㫆㪹㫌෻ᔕࠍⴕߞߚߣߎࠈ㧘 㪪_㪥㪉㶅ᚑ❣૕㪎㪏ߩ෼₸ߪ㪈㪍㧑ߦ߹ߢૐਅߒ㧘㪪_㪥㪉↢ᚑ‛

㪎㪎߇ਥᚑ❣૕ߦߥߞߚ㧚┙૕⊛ߦዊߐߥࠪࠕࡁၮࠍ㩷

TBDPSO F F

N NH

Me O

O TBDPSO F F

66

+

1) N

-benzoylthymine DIAD, Ph

P, THF 2) NH

/MeOH

74 (26%)

R

R

73D: R¹

= thymin-1-yl, R

= H (21%)

= H, R

= thymin-1-yl (20%)

Scheme 13. Mitsunobu reaction of 66. 㩷

㩷

᦭ߔࠆ㪎㪍ࠍၮ⾰ߣߒߡ↪޿ߚ႐วߦߪ㧘㪪_㪥㪉㶅ᚑ❣૕

㪎㪐ߩߺ߇↢ᚑߒߚ㧚৻ᣇ㧘ࡔ࠻ࠠࠪࠞ࡞ࡏ࠾࡞૕㪎㪈 ࠍ↪޿ߚ෻ᔕߢߪ 㪪_㪥㪉ᚑ❣૕㪏㪇ߩߺ߇ᓧࠄࠇ㧘෻ᔕ ߩ૏⟎ㆬᛯᕈࠍቢోߦ೙ᓮߔࠆߎߣ߇ߢ߈ߚ㧚㩷 ࡔ࠻ࠠࠪࠞ࡞ࡏ࠾࡞ၮߪᔅߕߒ߽߆ߐ㜞޿⟎឵ၮߣ ߪ⸒߃ߥ޿ߩߢ㧘㪏㪈㧔㪝㫀㪾㫌㫉㪼㩷㪍㧕ߩࠃ߁ߥࠛࠬ࠹࡞ࠞ

࡞ࡏ࠾࡞ၮߩ㓞ធၮ㑐ਈߦࠃߞߡ 㪪_㪥㪉㶅෻ᔕ߇㒖ᱛ ߐࠇߚߣ޿߁⠨߃ุ߽ቯߔࠆߎߣߪߢ߈ߥ޿㧚ߒ߆ ߒߥ߇ࠄ㧘㪎㪈ߩࠛࡇࡑ࡯ߢ޽ࠆ㪏㪉ࠍ⺞⵾ߒߡᧄ෻ᔕ ࠍⴕߞߚߣߎࠈ㧘㪪_㪥㪉ᚑ❣૕ߢ޽ࠆǩ㪄ࠕࡁࡑ࡯㪏㪊ߩ ߺ߇↢ᚑߒߚ㧚ᩭ㉄Ⴎၮߩ᳞ᩭ᡹᠄߇৻ᣇ⊛ߦ㪏㪈ߩ

㪺㫆㫅㪺㪸㫍㪼 㕙߆ࠄ⿠ߎߞߚߣߪ⠨߃㔍޿㧚ਛ㑆૕㪏㪈ߩ

ᄢ߈ߥᱡࠍ⠨ᘦߔࠆߣ㧘߿ߪࠅࡔ࠻ࠠࠪࠞ࡞ࡏ࠾࡞

ၮ߇ 㪪_㪥㪉㶅෻ᔕὐ߳ߩ┙૕㓚ኂࠍ߽ߚࠄߒߚߣ⠨߃ ࠆߩ߇ᅷᒰߢ޽ࠈ߁㧚㩷

㩷

OH R

TBDPSO F F

75 R = CH₂

OTBDPS

Me 1) N

-benzoylthymine DIAD, Ph

P, THF 2) K

CO

, MeOH or NH

/MeOH

R TBDPSO F F

N NH

Me O

O

TBDPSO F F R

+ N

NH Me

O O

77 R = CH₂

OTBDPS (41%)

Me (58%)

78 R = CH₂

OTBDPS (16%)

Scheme 14. Mitsunobu reaction of75, 76 and 71. 㩷 㩷

ᓧࠄࠇߚ㪏㪇ࠍ㪛㪠㪙㪘㪣㪄㧴ㆶర߅ࠃ߮㪦㪿㫀㫉㪸㪄㪙㪼㫊㫋㫄㪸㫅

⹜⮎ߦࠃࠅ㪎㪋㧔㪏㪇㧑㧕ߣߒߚᓟ㧘⣕ࠪ࡝࡞ൻߔࠆߎ ߣߦࠃࠅ⋡⊛ߣߔࠆ㪎㧔㪝㫀㪾㫌㫉㪼㪈㧕ࠍᓧࠆߎߣ߇ߢ߈ ߚ㧚ᧄൻว‛ߩ⋧ኻ┙૕㈩⟎ߪ㨄✢⚿᥏᭴ㅧ⸃ᨆߦ ࠃࠅ᳿ቯߒߚ㧔㪝㫀㪾㫌㫉㪼㪎㧕㧚㨄✢⚿᥏᭴ㅧ⸃ᨆߩ⚿ᨐ ࠍၮߦ㧘㪎ߩ┙૕㈩ᐳࠍ㪻㪋㪫㧔㪍㪊㧘㪝㫀㪾㫌㫉㪼㩷 㪌㧕ߩߘࠇ ߣᲧセߒߚ㧚ൻว‛㪎ߩࠣ࡝ࠦࠪ࡞⚿ว࿁ࠅߩߨߓࠇ㩷

O TBDPSO

F F

MeO MeO

C

TBDPSO F F

OH

MeO

C

TBDPSO F F

N N H

Me O O

82

83 81

Figure 6. Structures of compounds 81-83.

ⷺ㧔㪾㫃㫐㪺㫆㫊㫐㫃㩷 㫋㫆㫉㫊㫀㫆㫅㪸㫃㩷 㪸㫅㪾㫃㪼㪀㩷 㱣㩷 㩿㪚㪝_㪉㪄㪚㪈̡㪄㪥㪈㪄㪚㪉㪀ߪ 㪄㪐㪋㪅㪐㫦㩿㪄㪸㫅㫋㫀㪺㫃㫀㫅㪸㫃㧕 ߣ㪍㪊ߩ ߘ ࠇ 㧔 ǿ 㧩㪄㪈㪇㪇㪅㪏㫦㧘

㪦㪋㶅㪄㪚㪈㶅㪄㪥㪈㪄㪚㪉㧕^㪏㪉㧕ߦ㕖Ᏹߦㄭ޿߇㧘㪋㶅㪃㪌㶅㪄⚿ว

࿁ࠅߩߨߓࠇⷺ㧔㪚㪊㶅㪄㪚㪋㶅㪄㪚㪌㶅㪄㪦㪌㶅㪃㪄㫊㫐㫅㪺㫃㫀㫅㪸㫃㧘㱏 㧩㪄㪈㪋㪋㪅㪏㫦㪀ߪ㧘㪍㪊㩿㪂㫊㫐㫅㪺㫃㫀㫅㪸㫃㧘ǫ㧩㪌㪉㪅㪏q㪀ߣߪᄢ߈ ߊ⇣ߥࠆ㧚ߐࠄߦ㪎ߩࠪࠢࡠࡍࡦ࠹ࡦⅣߩࡄ࠶ࠞ࡝ࡦ

ࠣߦᵈ⋡ߔࠆߣ㧘㪚㪈㶅㪄㪚㪉㶅㪄㪚㪊㶅㪄㪚㪋㶅߆ࠄᚑࠆ㕙ߦ ኻߒߡࡈ࠶⚛ේሶߩ⟎឵ߒߚ㪚㪌㶅὇⚛߇࠴ࡒࡦႮၮ ᣇะߦ⓭಴ߒߡ߅ࠅ㧘߶߷ᐔ㕙ߢ޽ࠆ㪍㪊ߩ㪉㪃㪌㪄ࠫࡅ

࠼ࡠࡈ࡜ࡦⅣߣߪᄢ߈ߊ⇣ߥࠆߎߣ߇್᣿ߒߚ㧚㩷 એ਄ㅀߴߚࠃ߁ߦ㧘ࠫࡈࡠࡠ὇⚛Ⅳࠍ᦭ߔࠆ㪜㪻㪋㪫

⺃ዉ૕ߩวᚑߦߟ޿ߡᬌ⸛ߒߚ㧚૏⟎ㆬᛯ⊛ߥ࠴ࡒ ࡦ ߩ ዉ ౉ ߪ ࡔ ࠻ ࠠ ࠪ ࠞ ࡞ ࡏ ࠾ ࡞ ૕㪎㪈ࠍ ↪ ޿ ࠆ 㪤㫀㫋㫊㫌㫅㫆㪹㫌 ෻ ᔕ ߦ ࠃࠅ ㆐ᚑ ߒ ߚ㧚 ᱷᔨ ߥ ߇ࠄ㪎ߪ 㪟㪠㪭㪄㪈ߦኻߒߡჇᱺ㒖ኂᵴᕈࠍ␜ߐߥ߆ߞߚ㧚࠿ࠢ

࡟ࠝࠪ࠼⺃ዉ૕߇᛫ 㪟㪠㪭 ૞↪ࠍ⊒⃻ߔࠆߚ߼ߦߪ㧘

⚦⢩ౝࠠ࠽࡯࠯ߦࠃࠆ㪌㶅㪄ࡕࡁ࡝ࡦ㉄ൻࠍ⚻ߡ࠻࡝

࡝ ࡦ ㉄ߦ ᄌ឵ ߐ ࠇࠆ ߎߣ ߇ ᔅ㗇 ߣߐ ࠇ ߡ޿ ࠆ㧚

㪤㪸㫉㫈㫌㪼㫑 ࠄߪ㧘㪍㪊ߩࡈ࡜ࡁ࡯ࠬⅣ߇߶߷ᐔ㕙ߦㄭ޿

ߎߣ߇㧘ࠠ࠽࡯࠯ߦࠃࠆ⹺⼂ߦ㊀ⷐߥᓎഀࠍᨐߚߒ ߡ޿ࠆߣߩ⷗⸃ࠍឭ໒ߒߡ߅ࠅ㧘^㪏㪊㧕㪎߇ਇᵴᕈߢ޽

ࠆⷐ࿃ߩ৻ߟߣߒߡ਄ㅀߒߚ┙૕㈩ᐳߩ⋧㆑߇᜼ߍ ࠄࠇࠆߩߢߪߥ޿߆ߣផቯߒߡ޿ࠆ㧚㩷

⚿ ⺆

ᣂⷙ᛫࠙ࠗ࡞ࠬ೷ߩត⚝ࠍᔨ㗡ߦ߅޿ߡ㧘὇⚛Ⅳ

࠿ࠢ࡟ࠝࠪ࠼ߩ࠺ࠩࠗࡦߣวᚑ⎇ⓥࠍⴕߞߚ㧚ᧄ⎇

ⓥߩㆊ⒟ߦ߅޿ߡ㧘ᐞߟ߆ߩ᦭ᯏวᚑൻቇ⊛ߦ⥝๧

ᷓ޿⍮⷗߇ᓧࠄࠇߚ㧚⃻Ბ㓏ߢߪ㗼⪺ߥ᛫࠙ࠗ࡞ࠬ

૞↪ࠍ␜ߔൻว‛ࠍ⷗಴ߔߦߪ⥋ߞߡ޿ߥ޿߇㧘ᧄ

⎇ⓥ߇੹ᓟᣂⷙ᛫࠙ࠗ࡞ࠬ೷ࠍ㐿⊒ߔࠆߚ߼ߩ৻ഥ ߦߥࠆߎߣࠍᦼᓙߒߡ޿ࠆ㧚㩷

⻢ ㄉ

ᧄ⎇ⓥߪᤘ๺ᄢቇ⮎ቇㇱ⮎ຠ⵾ㅧൻቇᢎቶߦ߅޿

ߡⴕࠊࠇߚ߽ߩߢ޽ࠅ㧘ᓮᜰዉ㧘ᓮഥ⸒ࠍ⾦ࠅ߹ߒ ߚ↰ਛඳ㆏ᢎ᝼㧘ේญ৻ᐢಎᢎ᝼ߦෘߊᓮ␞↳ߒ਄

ߍ߹ߔ㧚ᧄ⺰ᢥߦ⸥タߒߚ⎇ⓥ⚿ᨐߪ㧘಴ญ৻⾆ୃ

჻㧘㜞ᯅ㊁ޘሶୃ჻㧘ਛ੗ 㓉ੱୃ჻㧘߅ࠃ߮ᒰ⎇

ⓥቶߦᚲዻߐࠇߚᄙߊߩቇㇱቇ↢⻉ำߩᒆ߹ߧദജ ߩ⾦‛ߢ޽ࠅ㧘ᷓߊᗵ⻢޿ߚߒ߹ߔ㧚㨄✢⚿᥏᭴ㅧ

⸃ᨆߪ㧘ਛ᧛๺㇢ᢎ᝼㧔ᤘ๺ᄢቇ⮎ቇㇱ㧕ߦߏදജ

޿ߚߛ߈߹ߒߚ㧚↢‛ᵴᕈ⹜㛎ߪ㚍႐᣽ᙗᢎ᝼㧔㣮 ఽፉᄢቇකቇㇱ㧘᛫ 㪟㪠㪭 ᵴᕈ㧕㧘ട⮮ትਯᢎ᝼㧔ጟ ጊᄢቇᄢቇ㒮කᱤቇ✚ว⎇ⓥ⑼㧘᛫㪟㪚㪭ᵴᕈ㧕㧘ർ

಴ᐘᄦᢎ᝼㧔ጘ㒂ᄢቇᎿቇㇱ㧘㪪㪘㪟㪸㫊㪼㒖ኂᵴᕈ㧕߅

ࠃ߮㪰㫌㫅㪾㪄㪚㪿㫀㩷㪚㪿㪼㫅㪾ᢎ᝼㧔☨ࠛ࡯࡞ᄢቇකቇㇱ㧘᛫

㪟㪠㪭ᵴᕈ㧕ߣߩ౒ห⎇ⓥߣߒߡߥߐࠇߚ߽ߩߢ޽ࠅ

߹ߔ㧚߹ߚᧄ⎇ⓥߩㆀⴕߦ޽ߚࠅߏេഥ޿ߚߛ޿ߚ ᣣᧄቇⴚᝄ⥝ળߦᷓ⻢↳ߒ਄ߍ߹ߔ㧔㪢㪘㪢㪜㪥㪟㪠㧦㩷 㪞㫉㪸㫅㫋㩷㫅㫌㫄㪹㪼㫉㩷㪈㪏㪎㪐㪇㪇㪐㪇㧕㧚㩷

ᢥ ₂

㪈㪀㩷 㪭㫀㫅㪺㪼㪃㩷㪩㪅㩷㪸㫅㪻㩷㪟㫌㪸㪃㩷㪤㪅㪑㩷㪪㫐㫅㫋㪿㪼㫊㫀㫊㩷㪸㫅㪻㩷㪸㫅㫋㫀㪄㪟㪠㪭㩷㪸㪺㫋㫀㫍㫀㫋㫐㩷㫆㪽㩷 㪺㪸㫉㪹㫆㪺㫐㪺㫃㫀㪺㩷 㶅㪃㪊㶅㪄㪻㫀㪻㪼㪿㫐㪻㫉㫆㪄㪉㶅㪃㪊㶅㪄㪻㫀㪻㪼㫆㫏㫐㪄㪉㪃㪍㪄㪻㫀㫊㫌㪹㫊㫋㫀 㫋㫌㫋㪼㪻㩷㫇㫌㫉㫀㫅㪼㩷㫅㫌㪺㫃㪼㫆㫊㫀㪻㪼㫊㪃㩷㪡㪅㩷㪤㪼㪻㪅㩷㪚㪿㪼㫄㪅㪃㩷㪊㪊㪃㩷㪈㪎㩿㪈㪐㪐㪇㪀㩷 㪉㪀㩷 㪙㫆㫉㪺㪿㪸㫉㪻㫋㪃㩷㪩㪅㩷㪫㪅㪃㩷㪢㪼㫃㫃㪼㫉㪃㩷㪙㪅㩷㪫㪅㩷㪸㫅㪻㩷㪧㪸㫋㪼㫉㪄㪫㪿㫆㫄㪹㫉㪼㪃㩷

㪬㪅㪑㩷 㪥㪼㫇㫃㪸㫅㫆㪺㫀㫅㩷 㪘㪅㩷 㪘㩷 㫇㫆㫋㪼㫅㫋㩷 㫀㫅㪿㫀㪹㫀㫋㫆㫉㩷 㫆㪽㩷 㪪㪄㪸㪻㪼㫅㫆㫊㫐㫃㪿㫆㫄㫆㪺㫐㫊㫋㪼㫀㫅㪼㩷㪿㫐㪻㫉㫆㫃㪸㫊㪼㩷㪸㫅㪻㩷㫆㪽㩷㫍㪸㪺㪺㫀㫅㫀㪸㩷 㫍㫀㫉㫌㫊㩷 㫄㫌㫃㫋㫀㫇㫃㫀㪺㪸㫋㫀㫆㫅㩷 㫀㫅㩷 㫄㫆㫌㫊㪼㩷 㪣㪐㪉㪐㩷 㪺㪼㫃㫃㫊㪃㩷 㪡㪅㩷 㪙㫀㫆㫃㪅㩷 㪚㪿㪼㫄㪅㪃㩷㪉㪌㪐㪃㩷㪋㪊㪌㪊㩿㪈㪐㪏㪋㪀㪅㩷

㪊㪀㩷 㪛㪸㫃㫌㪾㪼㪃㩷 㪪㪅㩷 㪤㪅㪑㩷 㪫㪿㪼㫉㪸㫇㪼㫌㫋㫀㪺㩷 㪥㫌㪺㫃㪼㫆㫊㫀㪻㪼㫊㪃㩷 㪬㪅㩷 㪪㪅㩷 㫇㪸㫋㪼㫅㫋㩿㪈㪐㪐㪈㪀㪃㩷㫇㪸㫋㪼㫅㫋㩷㫅㫌㫄㪹㪼㫉㩷㪌㪃㪇㪊㪋㪃㪊㪐㪋㪅㩷

㪋㪀㩷 㪢㫌㫄㪸㫄㫆㫋㫆㪃㩷 㪟㪅㪃㩷 㪛㪼㪾㫌㪺㪿㫀㪃㩷 㪢㪅㪃㩷 㪮㪸㪾㪸㫋㪸㪃㩷 㪫㪅㩷 㪼㫋㩷 㪸㫃㪅㪑㩷

㪩㪸㪻㫀㪺㪸㫃㪄㫄㪼㪻㫀㪸㫋㪼㪻㩷 㫊㫋㪸㫅㫅㫐㫃㪸㫋㫀㫆㫅㩷 㫆㪽㩷 㫍㫀㫅㫐㫃㫊㫌㫃㪽㫆㫅㪼㫊㪑㩷 㪸㪺㪺㪼㫊㫊㩷 㫋㫆㩷 㫅㫆㫍㪼㫃㩷 㪋㶅㪄㫄㫆㪻㫀㪽㫀㪼㪻㩷 㫅㪼㫇㫃㪸㫅㫆㪺㫀㫅㩷 㪘㩷 㪸㫅㪸㫃㫆㪾㫌㪼㫊㪃㩷㪫㪼㫋㫉㪸㪿㪼㪻㫉㫆㫅㪃㩷㪍㪌㪃㩷㪏㪇㪇㪎㩿㪉㪇㪇㪐㪀㪅㩷

㪌㪀㩷 㪩㪸㫅㫊㫆㪿㫆㪽㪽㪃㩷㪩㪅㩷㪤㪅㪃㩷㪥㪸㫉㪸㫐㪸㫅㪃㩷㪧㪅㪃㩷㪘㫐㪼㫉㫊㪃㩷㪛㪅㪃㩷㪝㪅㩷㪼㫋㩷㪸㫃㪅㪑㩷 㪧㫉㫀㫄㫀㫅㪾㩷 㫆㪽㩷 㫀㫅㪽㫃㫌㪼㫅㫑㪸㩷 㫄㪩㪥㪘㩷 㫋㫉㪸㫅㫊㪺㫉㫀㫇㫋㫀㫆㫅㩷 㫀㫊㩷 㫀㫅㪿㫀㪹㫀㫋㪼㪻㩷㫀㫅㩷㪚㪟㪦㩷㪺㪼㫃㫃㫊㩷㫋㫉㪼㪸㫋㪼㪻㩷㫎㫀㫋㪿㩷㫋㪿㪼㩷㫄㪼㫋㪿㫐㫃㪸㫋㫀㫆㫅㩷 㫀㫅㪿㫀㪹㫀㫋㫆㫉㪃㩷 㪥㪼㫇㫃㪸㫅㫆㪺㫀㫅㩷 㪘㪃㩷 㪘㫅㫋㫀㫍㫀㫉㪸㫃㩷 㫉㪼㫊㫊㪅㪃㩷 㪎㪃㩷 㪋㪈㪎㩿㪈㪐㪏㪎㪀㪅㩷

㪍㪀㩷 㪧㫌㪾㪿㪃㩷 㪚㪅㪪㪅㩷 㪞㪅㩷 㪸㫅㪻㩷 㪙㫆㫉㪺㪿㪸㫉㪻㫋㪃㩷 㪩㪅㩷 㪫㪅㪑㩷 㪜㪽㪽㪼㪺㫋㫊㩷 㫆㪽㩷 㪪㪄㪸㪻㪼㫅㫆㫊㫐㫃㪿㫆㫄㫆㪺㫐㫊㫋㪼㫀㫅㪼㩷 㪸㫅㪸㫃㫆㪾㫊㩷 㫆㫅㩷 㫍㪸㪺㪺㫀㫅㫀㪸㩷 㫍㫀㫉㪸㫃㩷 㫄㪩㪥㪘㩷㫊㫐㫅㫋㪿㪼㫊㫀㫊㩷㪸㫅㪻㩷㫄㪼㫋㪿㫐㫃㪸㫋㫀㫆㫅㪃㩷㪙㫀㫆㪺㪿㪼㫄㫀㫊㫋㫉㫐㪃㩷㪉㪈㪃㩷 㪈㪌㪊㪌㩿㪈㪐㪏㪉㪀㪅㩷 㩷

㪎㪀㩷 㪬㪼㫃㪸㫅㪻㪃㩷 㪧㪅㩷 㪤㪅㪑㩷 㪧㪿㪸㫉㫄㪸㪺㫆㫃㫆㪾㫀㪺㪸㫃㩷 㪸㫅㪻㩷 㪹㫀㫆㪺㪿㪼㫄㫀㪺㪸㫃㩷 㪸㫊㫇㪼㪺㫋㫊㩷 㫆㪽㩷 㪪㪄㪸㪻㪼㫅㫆㫊㫐㫃㪿㫆㫄㫆㪺㫐㫊㫋㪼㫀㫅㪼㩷 㪸㫅㪻㩷 㪪㪄㩷 㪸㪻㪼㫅㫆㫊㫐㫃㪿㫆㫄㫆㪺㫐㫊㫋㪼㫀㫅㪼㩷㪿㫐㪻㫉㫆㫃㪸㫊㪼㪃㩷㪧㪿㪸㫉㫄㪸㪺㫆㫃㪅㩷㪩㪼㫍㪅㪃㩷 㪊㪋㪃㩷㪉㪉㪊㩿㪈㪐㪏㪉㪀㪅㩷

㪏㪀㩷 㪧㫆㫉㫋㪼㫉㪃㩷 㪛㪅㩷 㪡㪅㩷 㪫㪅㩷 㪸㫅㪻㩷 㪙㫆㫐㪻㪅㩷 㪝㪅㩷 㪣㪅㪑㩷 㪤㪼㪺㪿㪸㫅㫀㫊㫄㩷 㫆㪽㩷 㪹㫆㫍㫀㫅㪼㩷 㫃㫀㫍㪼㫉㩷 㪪㪄㪸㪻㪼㫅㫆㫊㫐㫃㪿㫆㫄㫆㪺㫐㫊㫋㪼㫀㫅㪼㩷 㪿㫐㪻㫉㫆㫃㪸㫊㪼㪅㩷 㪪㫋㪼㪸㪻㫐㪄㫊㫋㪸㫋㪼㩷㪸㫅㪻㩷㫇㫉㪼㪄㫊㫋㪼㪸㪻㫐㪄㫊㫋㪸㫋㪼㩷㫂㫀㫅㪼㫋㫀㪺㩷㪸㫅㪸㫃㫐㫊㫀㫊㪃㩷 㪡㪅㩷㪙㫀㫆㫃㪅㩷㪚㪿㪼㫄㪅㪃㩷㪉㪍㪍㪃㩷㪉㪈㪍㪈㪍㩿㪈㪐㪐㪈㪀㪅㩷 㩷

㪐㪀㩷 㪛㪼㩷㪚㫃㪼㫉㪼㫈㪃㩷㪜㪅㪑㩷㪪㪄㪸㪻㪼㫅㫆㫊㫐㫃㪿㫆㫄㫆㪺㫐㫊㫋㪼㫀㫅㪼㩷㪿㫐㪻㫉㫆㫃㪸㫊㪼㩷 㫀㫅㪿㫀㪹㫀㫋㫆㫉㫊㩷 㪸㫊㩷 㪹㫉㫆㪸㪻㪄㫊㫇㪼㪺㫋㫉㫌㫄㩷 㪸㫅㫋㫀㫍㫀㫉㪸㫃㩷 㪸㪾㪼㫅㫋㫊㪃㩷 㪙㫀㫆㪺㪿㪼㫄㪅㩷㪧㪿㪸㫉㫄㪸㪺㫆㫃㪅㪃㩷㪊㪍㪃㩷㪉㪌㪍㪎㩿㪈㪐㪏㪍㪀㪅㩷 㩷

㪈㪇㪀㩷 㪮㫆㫃㪽㪼㪃㩷 㪤㪅㩷 㪪㪅㩷 㪸㫅㪻㩷 㪙㫆㫉㪺㪿㪸㫉㪻㫋㪃㩷 㪩㪅㩷 㪫㪅㪑㩷 㪪㪄㪘㪻㪼㫅㫆㫊㫐㫃㪄㪣㪄㪿㫆㫄㫆㪺㫐㫊㫋㪼㫀㫅㪼㩷㪿㫐㪻㫉㫆㫃㪸㫊㪼㩷㪸㫊㩷㪸㩷㫋㪸㫉㪾㪼㫋㩷㪽㫆㫉㩷 㪸㫅㫋㫀㫍㫀㫉㪸㫃㩷 㪺㪿㪼㫄㫆㫋㪿㪼㫉㪸㫇㫐㪃㩷 㪡㪅㩷 㪤㪼㪻㪅㩷 㪚㪿㪼㫄㪅㪃㩷 㪊㪋㪃㩷 㪈㪌㪉㪈㩿㪈㪐㪐㪈㪀㪅㩷 㩷

㪈㪈㪀㩷 㪟㪸㫊㫆㪹㪼㪃㩷㪤㪅㪃㩷㪤㪺㪢㪼㪼㪃㩷㪡㪅㩷㪞㪅㪃㩷㪙㫆㫉㪺㪿㪸㫉㪻㫀㫅㪾㪃㩷㪛㪅㩷㪩㪅㩷㪼㫋㩷㪸㫃㪅㪑㩷㪜㪽㪽㪼㪺㫋㫊㩷㫆㪽㩷 㪐㪄㩿㫋㫉㪸㫅㫊㪄㪉㶅㪃㫋㫉㪸㫅㫊㪄㪊㶅㪄㪻㫀㪿㫐㪻㫉㫆㫏㫐㪺㫐㪺㫃㫆㫇㪼㫅㫋㪄㪋㶅㪄㪼㫅㫐㫃㪀㪄 㪸㪻㪼㫅㫀㫅㪼㩷 㪸㫅㪻㩷 㪄㪊㪄㪻㪼㪸㫑㪸㪸㪻㪼㫅㫀㫅㪼㩷 㫆㫅㩷 㫋㪿㪼㩷 㫄㪼㫋㪸㪹㫆㫃㫀㫊㫄㩷 㫆㪽㩷 㪪㪄㪸㪻㪼㫅㫆㫊㫐㫃㪿㫆㫄㫆㪺㫐㫊㫋㪼㫀㫅㪼㩷 㫀㫅㩷 㫄㫆㫌㫊㪼㩷 㪣㪐㪉㪐㩷 㪺㪼㫃㫃㫊㪃㩷 㪤㫆㫃㪅㩷 㪧㪿㪸㫉㫄㪸㪺㫆㫃㪅㪃㩷㪊㪊㪃㩷㪎㪈㪊㩿㪈㪐㪏㪏㪀㪅㩷 㩷

㪈㪉㪀㩷 㪪㪿㫌㫋㫆㪃㩷 㪪㪅㪃㩷 㪦㪹㪸㫉㪸㪃㩷 㪫㪅㪃㩷 㪫㫆㫉㫀㫐㪸㪃㩷 㪤㪅㩷 㪼㫋㩷 㪸㫃㪅㪑㩷 㪥㪼㫎㩷 㫅㪼㫇㫃㪸㫅㫆㪺㫀㫅㩷 㪸㫅㪸㫃㫆㪾㫊㪅㩷 㪈㪅㩷 㪪㫐㫅㫋㪿㪼㫊㫀㫊㩷 㫆㪽㩷 㪍㶅㪄㫄㫆㪻㫀㪽㫀㪼㪻㩷 㫅㪼㫇㫃㪸㫅㫆㪺㫀㫅㩷 㪘㩷 㪻㪼㫉㫀㫍㪸㫋㫀㫍㪼㫊㩷 㪸㫊㩷 㪹㫉㫆㪸㪻㪄㫊㫇㪼㪺㫋㫉㫌㫄㩷 㪸㫅㫋㫀㫍㫀㫉㪸㫃㩷㪸㪾㪼㫅㫋㫊㪃㩷㪡㪅㩷㪤㪼㪻㪅㩷㪚㪿㪼㫄㪅㪃㩷㪊㪌㪃㩷㪊㪉㪋㩿㪈㪐㪐㪉㪀㪅㩷 㪈㪊㪀㩷 㪙㫆㫉㪺㪿㪸㫉㪻㫀㫅㪾㪃㩷㪛㪅㩷㪩㪅㪃㩷㪪㪺㪿㫆㫀㫋㫑㪃㩷㪪㪅㩷㪘㪅㩷㪸㫅㪻㩷㪙㫆㫉㪺㪿㪸㫉㪻㫋㪃㩷

㪩㪅㩷 㪫㪅㪑㩷 㪪㫐㫅㫋㪿㪼㫊㫀㫊㩷 㫆㪽㩷 㪸㫅㪸㫃㫆㪾㫊㩷 㫆㪽㩷 㫅㪼㫇㫃㪸㫅㫆㪺㫀㫅㩷 㪘㪑㩷 㫌㫋㫀㫃㫀㫑㪸㫋㫀㫆㫅㩷 㫆㪽㩷 㫆㫇㫋㫀㪺㪸㫃㫃㫐㩷 㪸㪺㫋㫀㫍㪼㩷 㪻㫀㪿㫐㪻㫉㫆㫏㫐㪺㫐㪺㫃㫆㫇㪼㫅㫋㪼㫅㫆㫅㪼㫊㩷 㪻㪼㫉㫀㫍㪼㪻㩷 㪽㫉㫆㫄㩷 㪺㪸㫉㪹㫆㪿㫐㪻㫉㪸㫋㪼㫊㪃㩷 㪡㪅㩷 㪦㫉㪾㪅㩷 㪚㪿㪼㫄㪅㪃㩷 㪌㪉㪃㩷 㪌㪋㪌㪎㩿㪈㪐㪏㪎㪀㪅㩷