糖鎖－蛋白質複合体のX線結晶構造解析のためのセレン標識糖鎖プローブの開発

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Title

糖鎖−蛋白質複合体のX線結晶構造解析のためのセレン標

_{識糖鎖プローブの開発( 本文(Fulltext) )}

Author(s)

鈴木, 達哉

Report No.(Doctoral

Degree)

博士(農学) 甲第631号

Issue Date

2014-03-31

Type

博士論文

Version

ETD

URL

http://hdl.handle.net/20.500.12099/49111

※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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⢾㙐⺮ⓑ㉁」ྜయࡢ㹖⥺⤖ᬗᵓ㐀ゎᯒࡢࡓࡵࡢ

ࢭࣞࣥᶆ㆑⢾㙐ࣉ࣮ࣟࣈࡢ㛤Ⓨ

㸰㸮㸯㸱ᖺ

ᒱ㜧኱Ꮫ኱Ꮫ㝔㐃ྜ㎰Ꮫ◊✲⛉

⏕≀㈨※⛉Ꮫ

㸦ᒱ㜧኱Ꮫ㸧

㕥ᮌ 㐩ဢ

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␎ ␎ྕ⾲

Ac : acetyl

AW-300 : acid washed 4Å molecular sieves BDA : benzaldehyde dimethylacetal

Bn : benzyl

Bz : benzoyl

Bzld : benzylidene

Cp : cyclopentadienyl

CSA : DL-10-camphorsulfonic acid DAST : N,N-diethylaminosulfur trifluoride

DIEA : N,N-diisopropylethylamine DMAP : 4-dimethylaminopyridine DMF : N,N-dimethylformamide Gal : galactose Glc : glucose Imdt : trichloroacetoimidoyloxy Me : methyl MPM : 4-methoxyphenylmethyl MS3Å : 3 Å molecular sieves MS4Å : 4 Å molecular sieves NIS : N-iodosuccinimide Ph : phenyl Pyr : pyridine SE : 2-(trimethylsilyl)ethyl

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- 2 - TBAF : tetra-n-butylanmonium fluroide

TEA : triethylamine Tf : trifluoromethanesulfonyl TFAc : trifluoroacetyl THF : tetrahydrofuran TMS : trimethylsilyl Tol : p-methylbenzoyl Ts : p-toluenesulfonyl

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┠ ┠ḟ ⥴ゝ 05 ➨1㒊 ୍⣭Ỉ㓟ᇶ⨨᥮ᆺࢭࣞࣀࣛࢡࢺ࣮ࢫࡢྜᡂ࡜X ⥺⤖ᬗᵓ㐀ゎᯒ 08 ➨1❶ ศᏊタィ࡜ྜᡂᡓ␎ 08 ➨2❶ 6’-ࢭࣞࣀࣛࢡࢺ࣮ࢫࡢྜᡂ 13 ➨1⠇ ࢭࣞࣀ࢞ࣛࢡࢺ࣮ࢫ౪୚యࡢྜᡂ 13 ➨2⠇ 6’-ࢭࣞࣀࣛࢡࢺ࣮ࢫࡢᵓ⠏ 15 ➨3❶ 6-ࢭࣞࣀࣛࢡࢺ࣮ࢫࡢྜᡂ 20 ➨1⠇ ࢭࣞࣀࢢࣝࢥ࣮ࢫཷᐜయࡢྜᡂ 20 ➨2⠇ 6-ࢭࣞࣀࣛࢡࢺ࣮ࢫࡢᵓ⠏ 21 ➨4❶ SPR ἲ࡟ࡼࡿࣄࢺ࢞ࣞࢡࢳࣥ-9 NCRD ࡜ࡢ⤖ྜヨ㦂 23 ➨5❶ ࢭࣞࣥᶆ㆑⢾㙐࡬ࡢ MAD ἲࡢ㐺⏝࡜ඹ⤖ᬗ X ⥺ᵓ㐀ゎᯒ 25 ⥲ᣓ 28

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- 4 - ➨2㒊 ࢔ࢭࢱ࣮ࣝ஺᥮཯ᛂࢆ฼⏝ࡍࡿ᪂つࢭࣞࣥᑟධ཯ᛂࡢ㛤Ⓨ 29 ➨1❶ ᪂つࢭࣞࣥᑟධ཯ᛂࡢ㛤Ⓨᡓ␎ 29 ➨2❶ ┤㙐ᆺࢭࣞࣀ࢔ࢭࢱ࣮ࣝヨ⸆ࡢ㛤Ⓨ 31 ➨3❶ ࢭࣞࣥከ⨨᥮⢾㙐ࡢྜᡂ 36 ➨1⠇ ࢭࣞࣥከ⨨᥮⢾㙐ࡢྜᡂᡓ␎ 36 ➨2⠇ ࣓ࢳࣝࢭࣞࣀᇶࢆ᭷ࡍࡿồ᰾๣ࡢ㛤Ⓨ 38 ➨3⠇ ࢺࣜࢭࣞࣀࢩ࢔ࣜࣝD(2-6)࢞ࣛࢡࢺ࣮ࢫࡢྜᡂ 41 ⥲ᣓ 42 ࡲ࡜ࡵ 43 ᐇ㦂ࡢ㒊 44 ㅰ㎡

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⥴ ⥴ゝ ᰾㓟ࠊ⺮ⓑ㉁࡟⥆ࡃ➨୕ࡢ⏕࿨㙐࡛࠶ࡿ⢾㙐ࡣࠊ⏕యෆ࡛ࡣ⣽⬊⾲ᒙ࡟ከࡃᏑᅾࡋࠊᵝࠎ ࡞⏕࿨⌧㇟ࠊ౛࠼ࡤࠊ⣽⬊㛫ࡢࢩࢢࢼࣝఏ㐩ࠊ⑓ཎ⳦ࡸ࢘࢕ࣝࢫࡢឤᰁ࡞࡝࡟㛵୚ࡋ࡚࠸ ࡿࠋࡇࡢࡼ࠺࡞⢾㙐ࡢ㧗ḟᶵ⬟Ⓨ⌧࡟࠾࠸࡚ࡣࠊ⢾㙐-⢾㙐ࡲࡓࡣࠊ⢾㙐-⺮ⓑ㉁ࡢ┦஫స⏝ ࢆ௓ࡋࡓ⢾㙐࡜ㄆ㆑ཷᐜయ࡜ࡢ」ྜయࡢᙧᡂࡀ㔜せ࡛࠶ࡾࠊࡑࡢㄆ㆑」ྜయࡢ❧యᵓ㐀᝟ ሗࡢྲྀᚓࡣࠊศᏊ࡛ࣞ࣋ࣝࡢ⢾㙐ࡢ⏕≀Ꮫⓗព⩏ࡢゎ᫂࡟࠾࠸࡚୙ྍḞ࡛࠶ࡿࠋࡇࢀࡲ࡛ ࡟ᙜ◊✲ᐊ࡛ࡣࠊ᭷ᶵ໬Ꮫⓗ࡟ྜᡂࡋࡓ⢾㙐࡜ࠊࢩ࢔ࣝ㓟ㄆ㆑⺮ⓑ㉁ Siglec71_{ࠊ⣽⳦ẘ⣲}

Tetanus Toxin2ࠊBotulinus Toxin3ࡸ࣓ࣝࢣࣝ⣽⬊࣏࣮࣐ࣜ࢜࢘࢕ࣝࢫ4࡜ࡢ⢾㙐-⺮ⓑ㉁」ྜయ

ࡢඹ⤖ᬗࢆసᡂࡋ X ⥺⤖ᬗᵓ㐀ゎᯒࢆ⾜࠺ࡇ࡜࡛ࠊㄆ㆑ᶵᵓࡢゎ᫂ࠊస⏝ᶵᵓࡢゎ᫂࡟⧅

ࡆ࡚ࡁ࡚࠾ࡾࠊ⢾㙐ㄆ㆑ᶵᵓࡢゎ᫂࡟ࡣࡇࡢࡼ࠺࡞ᵓ㐀⏕≀Ꮫⓗ࡞࢔ࣉ࣮ࣟࢳࡀ᭷ຊ࡛࠶ ࡿࡇ࡜ࢆド᫂ࡋ࡚ࡁࡓࠋ

⺮ⓑ㉁ࡢ❧యᵓ㐀ゎᯒ࡛ࡣࠊࢭࣞࣥཎᏊ≉᭷࡞ X ⥺ᩓ஘ᙉᗘࡢἼ㛗౫Ꮡᛶࢆ฼⏝ࡋ఩┦

Ỵᐃࢆ⾜࠺ࠊከἼ㛗␗ᖖศᩓἲ (Multi-wavelength Anomalous Diffraction method : MAD ἲ

(Figure 1))5ࡀ࠶ࡾࠊ1990 ᖺ௦㡭࠿ࡽ┒ࢇ࡟⾜࡞ࢃࢀࡿࡼ࠺࡟࡞ࡗ࡚ࡁࡓࠋᚑ᮶ἲ࡛࠶ࡿ㔜

ཎᏊྠᆺ⨨᥮ἲ (Multiple Isomorphous Replacement method: MIR ἲ)࡟ẚ࡭࡚ࠊᅔ㞴࡛࠶ࡗࡓ ⺮ⓑ㉁⤖ᬗࡢ㔜ཎᏊ⨨᥮ࡢᚲせࡀ↓ࡃ࡞ࡾࠊࢭࣞࣥཎᏊ⨨᥮ᆺ⺮ⓑ㉁ࡢ⤖ᬗࡢㄪ〇ࢆ⾜࠸

ከἼ㛗ࡢ X ⥺ࢆ⏝࠸ࡿࡢࡳ࡛⺮ⓑ㉁ࡢᵓ㐀᝟ሗࢆᚓࡽࢀࡿࡓࡵࠊ⺮ⓑ㉁ࡢ❧యᵓ㐀Ỵᐃᩘ

ࢆ㣕㌍ⓗ࡟ቑ኱ࡉࡏࡓࠋ

ࡋ࠿ࡋ࡞ࡀࡽࠊࡇࡢMAD ἲ࡟ࡶ஧ࡘࡢၥ㢟ࡀᏑᅾࡋ࡚࠸ࡿࠋ୍ࡘ┠ࡣࢭࣞࣥᶆ㆑⺮ⓑ㉁

1_{H. Attrill, A. Imamura, R. S. Sharma, M. Kiso, P. R. Crocker, D. M. F. van Aalten, J. Biol. Chem.} 2006, 281, 32774-32783.

2_{C. Fotinou, P. Emsley, I. Black, H. Ando, H. Ishida, M. Kiso, K. A. Sinha, N. F. Fairweather, N. W.}

Isaacs, J. Biol. Chem. 2001, 276, 32274-32281.

3_{P. Stenmark, J. Dupuy, A. Imamura, M. Kiso, R. C. Stevens,}_{PLoS Pathogens 2008, 4, e1000129.} 4_{U. Neu, H. Hengel, B. S. Blaum, R. M. Schowalter, D. Macejak, M. Gilbert, W. W. Wakarchuk, A.}

Imamura, H. Ando, M. Kiso, N. Arnberg, R. L. Garcea, T. Peters, C. B. Buck, T. Stehle, PLoS

Pathogens 2012, 8, e1002738.

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- 6 - ࡢㄪ〇ࡀࡋࡤࡋࡤᅔ㞴໬ࡍࡿⅬ࡛࠶ࡿࠋMAD ἲࡢ㐺⏝࡟࠾࠸࡚ࡣࠊ㑇ఏᕤᏛⓗ࡞᧯స࡟ࡼ ࡾࢭࣞࣥᶆ㆑⺮ⓑ㉁ࢆㄪ〇ࡍࡿᚲせࡀ࠶ࡾࠊ⺮ⓑ㉁ࢆࢥ࣮ࢻࡍࡿࣜࢥࣥࣅࢼࣥࢺDNA ࡢྲྀ ᚓࠊ࣋ࢡࢱ࣮࡟ࡼࡿ኱⭠⳦࡬ࡢᑟධࠊ኱⭠⳦ᇵ㣴ࠊ⺮ⓑ㉁ࡢ⢭〇࡜ࠊከᕤ⛬ࢆせࡋࠊ㛗࠸ ᫬㛫ࢆ㈝ࡸࡍሙྜࡶከ࠸ࠋຍ࠼࡚ࠊࢭࣞࣥᶆ㆑⺮ⓑ㉁ࡢⓎ⌧㔞ࡀᴫࡋ࡚పࡃࠊ࡜ࡾࢃࡅ᪻ ⹸⣽⬊ࡸࣄࢺ⣽⬊ࡢⓎ⌧⣔࡛ࡣ㈝⏝ࡀ㧗㢠࡟࡞ࡿࡇ࡜ࡶࡋࡤࡋࡤၥ㢟࡜ࡉࢀ࡚࠸ࡿࠋ ஧ࡘ┠࡟ࡣࠊࢭࣞࣥᶆ㆑࡟ࡼࡾ⺮ⓑ㉁ࡢ≀ᛶࡀኚ໬ࡍࡿྍ⬟ᛶࡢⅬࡀᣲࡆࡽࢀࡿࠋࢭࣞ ࣥᶆ㆑⺮ⓑ㉁ࡣࠊࡶ࡜ࡢ⺮ⓑ㉁࡜ẚ࡭⺮ⓑ㉁ࡢ⬤ᙅ໬ࠊ⤖ᬗᛶࡢపୗࠊ❧యᵓ㐀ࡢኚ໬ࡀ ⏕ࡌࡿሙྜࡀ࠶ࡿࠋ Figure 1 MAD ἲἲࡢᴫᛕᅗ ㏆ᖺ Huang ࡽ6ࡣࠊDNA ࡢ⤖ᬗᵓ㐀ゎᯒ࡟࠾࠸࡚ࠊ᰾㓟ࡢ 2’఩ࡸࣜࣥ㓟࢚ࢫࢸࣝ㒊఩࡟

࠶ࡽ࠿ࡌࡵࢭࣞࣥཎᏊࢆᑟධࡋ MAD ἲ࡟ࡼࡿ DNA ⤖ᬗᵓ㐀ゎᯒ࡟ᡂຌࡋ࡚࠾ࡾࠊMAD

ἲࡢᛂ⏝⠊ᅖࡀᗈࡀࡗ࡚ࡁ࡚࠸ࡿࠋ

ࡲࡓࠊButs ࡽ7ࡣࢭࣞࣀࢢࣝࢥࢧ࣑ࣥㄏᑟయࢆ⏝࠸࡚ E. coli ⏤᮶ࡢ⢾⤖ྜ⺮ⓑ㉁ F-17G

adhesin ࡜ࡢඹ⤖ᬗࡢᵓ㐀ゎᯒ࡟ࠊ㰺㔝ࡽ8ࡣࢭࣞࣀ࣐ࣝࢺࢩࢻㄏᑟయࢆ⏺㠃άᛶ๣࡜ࡋ࡚⏝

࠸࡚⭷⺮ⓑ㉁Leukotriene C4 synthase ࡜ࡢඹ⤖ᬗࡢᵓ㐀ゎᯒ࡟ᡂຌࡋ࡚࠸ࡿ (Figure 2)ࠋ

6_{a) Q. Du, N. Carrsco, M. Teplova, C. J. Wilds, M. Egli, Z. Huang, J. Am. Chem. Soc. 2002, 124, 24.}

b) N. Carrasco, Z. Huang, J. Am. Chem. Soc. 2004, 126, 448. c) J. Salon, G. Chen, Y. Portilla, M. W. Germann, Z. Huang, Org. Lett. 2005, 7, 5645. d) J. Salon, J. Sheng, J. JIang, G. Chen, J. Caton-Williams, Z. Huang, J. Am. Chem. Soc. 2007, 129, 4862.

7_{L. Buts, R. Loris, E. De Genst, S. Oscarson, M. Lahmann, J. Messens, E. Brosens, L. Wyns, H. De}

Greve, J. Bouckaert, Acta. Cryst. 2003, D59, 1012-1015.

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Figure 2 ࡇࡢࡼ࠺࡟ࠊ⢾㙐-⺮ⓑ㉁」ྜయࡢ X ⥺⤖ᬗᵓ㐀ゎᯒ࡟࠾࠸࡚ࡶࢭࣞࣀ⢾ࢆ⏝࠸ࡿࡇ࡜࡛ ⺮ⓑ㉁ࢆຍᕤࡍࡿࡇ࡜࡞ࡃMAD ἲࡀ㐺⏝ྍ⬟࡛࠶ࡿࡇ࡜ࡀ♧ࡉࢀ࡚ࡁ࡚࠸ࡿࠋ ࡋ࠿ࡋ࡞ࡀࡽࠊ⢾㙐ࡢࢭࣞࣥᶆ㆑ࡀศᏊᵓ㐀ࠊ໬Ꮫⓗ࣭≀ᛶᏛⓗᛶ㉁࡟୚࠼ࡿᙳ㡪ࡣࠊ ⣔⤫ⓗ࡟᳨ドࡉࢀ࡚࠾ࡽࡎࠊࢭࣞࣀ⢾㙐ࢆ⏝࠸ࡓMAD ἲࡢ㐺⏝㝈⏺࡞࡝᫂ࡽ࠿࡜ࡉࢀ࡚࠸ ࡞࠸ࠋࡇࢀࡣࠊ୺࡟ࢭࣞࣀ⢾㙐ࡢྜᡂἲࡀ☜❧ࡋ࡚࠸࡞࠸ࡇ࡜࡟㉳ᅉࡋ࡚࠸ࡿ࡜⪃࠼ࡽࢀ ࡿࠋ ࡑࡇ࡛ࠊᮏ◊✲࡛ࡣࢭࣞࣥᶆ㆑⢾㙐ࡢྜᡂἲࢆ☜❧ࡋMAD ἲ࡟࠾ࡅࡿࢭࣞࣥᶆ㆑⢾㙐ࡢ ᭷ຠᛶࢆ᳨ドࡍࡿࡇ࡜ࢆ┠ⓗ࡜ࡋࡓࠋ➨ 1 㒊࡛ࡣ୍⣭Ỉ㓟ᇶ⨨᥮ᆺࣛࢡࢺ࣮ࢫࡢྜᡂ࡜ MAD ἲࢆ⏝࠸ࡓ X ⥺⤖ᬗᵓ㐀ゎᯒ࡬ࡢ㐺⏝ࢆ⾜࠺ࡇ࡜࡜ࡋࠊ➨ 2 㒊࡛ࡣࠊ኱ᆺࡢ⺮ⓑ㉁ゎ ᯒ࡬ࡢMAD ἲࡢ㐺⏝࡟ྥࡅ࡚᪂つࡢࢭࣞࣀࢢࣜࢥࢩࢻᵓ⠏ἲࡢ㛤Ⓨࢆ⾜࠺ࡇ࡜࡜ࡋࡓࠋ

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- 8 - ➨ ➨㸯㒊 ୍⣭Ỉ㓟ᇶ⨨᥮ᆺࢭࣞࣀࣛࢡࢺ࣮ࢫࡢྜᡂ࡜ X ⥺⤖ᬗᵓ㐀ゎᯒ ➨㸯❶ ศᏊタィ࡜ྜᡂᡓ␎ ࡇࢀࡲ࡛࡟ᙜ◊✲ᐊ࡛ࡣࢢࣜࢥࢩࢻ⤖ྜࡢ㓟⣲ཎᏊࢆࢭࣞࣥཎᏊ࡟⨨᥮ࡋࡓ⢾㙐ࡢྜᡂ ࢆሗ࿌ࡋ࡚࠸ࡿ9ࠋࡋ࠿ࡋ࡞ࡀࡽࠊࢭࣞࣥཎᏊ࡟ࡼࡿ⨨᥮ࡀࢢࣜࢥࢩࢻ⤖ྜࡢゅᗘࠊ㊥㞳ࢆ ኚ໬ࡉࡏ❧యᵓ㐀ࡢኚᙧ࡟ࡼࡿ⺮ⓑ㉁ࡢㄆ㆑࡬ࡢᙳ㡪ࡀฟࡿࡇ࡜ࡀᠱᛕࡉࢀࡿࠋࡑࡇ࡛ࠊ ❧యᵓ㐀ࡢಖᣢࡢࡓࡵ࡟ࡣࢢࣜࢥࢩࢻ⤖ྜ࡟ྵࡲࢀ࡞࠸Ỉ㓟ᇶࡢ㓟⣲ࢆࢭ࡛ࣞࣥ⨨᥮ࡍࡿ ᪉ࡀ᭷฼࡜⪃࠼ࡽࢀࡿࡀࠊࡇࡢሙྜ࡛ࡶᯝࡓࡋ࡚⢾㙐ࣜ࢞ࣥࢻࡢ࣑࣑ࢵࢡ࡜ࡋ࡚ṇࡋࡃ⺮ ⓑ㉁࡟ㄆ㆑ࡉࢀࡿ࠿ࡣ౫↛࡜ࡋ࡚୙࡛᫂࠶ࡿࠋ ࡑࡇ࡛ᮏ◊✲࡛ࡣࠊࣛࢡࢺ࣮ࢫࠊࣛࢡࢺࢧ࣑ࣥࠊࣛࢡࢺࢧ࣑ࣥ஧㔞య࡞࡝࡜ࡢࠊX ⥺⤖ᬗ ᵓ㐀ゎᯒࡀࡍ࡛࡟ሗ࿌ࡉࢀࠊࡑࡢ⢾㙐ㄆ㆑ᶵᵓ࡟ࡘ࠸࡚ࡶヲ⣽࡟ゎᯒࡉࢀ࡚࠸ࡿ࢞ࣞࢡࢳ ࣥ-9 ࢆ⢾㙐⤖ྜ⺮ⓑ㉁ࡢࣔࢹࣝ࡜ࡋ࡚╔┠ࡋࠊࢭࣞࣀ⢾㙐࡟ᑐࡍࡿㄆ㆑ࢆ᳨ドࡍࡿࡇ࡜࡜ ࡋࡓ (Figure 3) 10_ࠋ Figure 3 ࢞ࣞࢡࢳࣥ-9 ࡢ❧యᵓ㐀 ࢞ࣞࢡࢳࣥ-9 ࡣ 353 ࢔࣑ࣀ㓟ṧᇶࠊศᏊ㔞⣙ 40 kDa ࠿ࡽ࡞ࡾࠊ1998 ᖺ࡟ዲ㓟⌫ࡢ㐟㉮ά ᛶ࡟㛵୚ࡍࡿ࢚࢝ࣞࢡࢳࣥ࡜ࡋ࡚ྠᐃࡉࢀࠊච␿⣽⬊࡟ከࡃⓎ⌧ࡋࠊ⅖⑕ࡸ⭘⒆࡟῝ࡃ㛵 ࢃࡗ࡚࠸ࡿࡇ࡜ࡀሗ࿌ࡉࢀ࡚࠸ࡿࠋ࢞ࣞࢡࢳࣥ-9 ࢆྵࡴ࢞ࣞࢡࢳࣥࡢ୍⩌11ࡣື≀ࣞࢡࢳࣥ ࣇ࢓࣑࣮ࣜࡢ୰࡛ࠊE(1→4)࢞ࣛࢡࢺࢩࢻ⤖ྜࢆㄆ㆑ࡍࡿ୍⩌࡜ᐃ⩏ࡉࢀ࡚࠾ࡾࠊከ⢾୰ࡢ

9_{a) Y. Kawai, H. Ando, H. Ozeki, M. Koketsu, H. Ishihara, Org. Lett. 2005, 7, 4653-4656. b) M.}

Nanami, H. Ando, Y. Kawai, M. Koketsu, H. Ishihara, Tetrahedron Lett. 2007, 48, 1113-1116.

10_{M. Nagae, N. Nishi, S. Nakamura-Tsuruta, J. Hirabayashi, S. Wakatsuki, R. Kato, J. Mol. Biol.} 2008, 375, 119-135.

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E(1→4)࢞ࣛࢡࢺࢩࢻ⤖ྜࢆࡶㄆ㆑ࡍࡿࡇ࡜ࡀྍ⬟࡛࠶ࡿࠋᮏ◊✲࡛ࡣࠊ࢞ࣞࢡࢳࣥ-9 ࡀㄆ ㆑ࡍࡿ᭱ᑠࡢࣜ࢞ࣥࢻᵓ㐀ࡢ1 ࡘ࡛࠶ࡿࣛࢡࢺ࣮ࢫࡢࢭࣞࣥᶆ㆑యࢆྜᡂࡍࡿࡇ࡜࡜ࡋࡓࠋ ࣛࢡࢺ࣮ࢫࡣࣄࢺ⏤᮶࢞ࣞࢡࢳࣥ-9 ࡢ࢔࣑ࣀ㓟ṧᇶ࡜Ỉ⣲⤖ྜࢆ௓ࡋ࡚ࠊ࢞ࣛࢡࢺ࣮ࢫ ṧᇶࡢ4 ఩Ỉ㓟ᇶࠊ6 ఩Ỉ㓟ᇶࡢ㡰࡛ᙉࡃㄆ㆑ࡉࢀࡿࡇ࡜ࡀ▱ࡽࢀ࡚࠸ࡿ (Figure 4)ࠋᮏ◊ ✲࡛ࡣࠊㄆ㆑࡟㛵ࢃࡿỈ㓟ᇶࡢ㓟⣲ࢆᩒ࠼࡚ࢭࣞࣥ࡟⨨᥮ࡍࡿࡇ࡜࡛ࠊࢭࣞࣥ⨨᥮ࡢཬࡰ ࡍ⢾㙐ㄆ㆑࡬ࡢᙳ㡪ࢆㄪ࡭ࡿࡇ࡜࡜ࡋࡓࠋࡋ࠿ࡋࠊỈ㓟ᇶ (OH)࡟ᑐᛂࡍࡿࢭࣞࣀ࣮ࣝ (SeH)ࡣᐜ᫆࡟㓟໬ࡉࢀ࡚ࢪࢭࣞࢽࢻ⤖ྜࢆᙧᡂࡍࡿࡓࡵࠊಖㆤᇶ࡜ࡋ࡚❧య㞀ᐖࡀ᭱ᑠࡢ ࣓ࢳࣝᇶࢆᑟධࡍࡿࡇ࡜࡜ࡋࠊMeSe ᇶ࡛Ỉ㓟ᇶࢆ⨨᥮ࡍࡿࡇ࡜࡜ࡋࡓࠋࡲࡓࠊࢭ࡛ࣞࣥ⨨ ᥮ࡍࡿ఩⨨࡜ࡋ࡚ࠊ❧యⓗ࡞㞀ᐖࡀᑠࡉࡃࠊ࢔࢟ࣛࣝ࡞Ⅳ⣲࡛࠶ࡿ6 ఩ཬࡧ 6’఩ࢆ㑅ᢥࡋࠊ MeSe ࡛⨨᥮ࡋࡓࢭࣞࣀࣛࢡࢺ࣮ࢫ㢮⦕యࢆ┠ⓗ໬ྜ≀࡜タᐃࡋࡓࠋ Figure 4 ࣄࢺ࢞ࣞࢡࢳࣥ-9 ࡢㄆ㆑ࡍࡿ⢾ࡢỈ㓟ᇶ ࡲࡓࠊྜᡂࡋࡓࢭࣞࣀࣛࢡࢺ࣮ࢫࡣ๓㏙ࡢ㏻ࡾ࢞ࣞࢡࢳࣥ-9 ࡟ࣜ࢞ࣥࢻ࡜ࡋ࡚ㄆ㆑ࡉࢀ ࡿ࠿࡝࠺࠿ࡢ᳨ドࢆ⾜࠺ᚲせࡀ࠶ࡾࠊࡑࡢゎᯒᡭἲ࡜ࡋ࡚ᮏ◊✲࡛ࡣ⾲㠃ࣉࣛࢬࣔࣥඹ㬆 ἲ (SPR ἲ)ࢆ㑅ᢥࡍࡿࡇ࡜࡜ࡋࡓࠋࡑࡢࡓࡵࠊྜᡂࡋࡓࢭࣞࣀ⢾㙐ࢆࢭࣥࢧ࣮ࢳࢵࣉୖ࡬ ᅛᐃ໬ࡍࡿࡓࡵ࡟ࠊ࢔࣑ࣀᇶࢆ᭷ࡍࡿ࣮ࣜࣥ࢝ࢆᑟධࡋࡓ໬ྜ≀ࡶྜᡂࡍࡿࡇ࡜࡜ࡋࡓࠋ ௨ୖࡼࡾࠊ┠ⓗࡢ໬ྜ≀ࡣ࢞ࣛࢡࢺ̿ࢫ 6 ఩࣓ࢳࣝࢭࣞࣀᇶ⨨᥮ࣛࢡࢺ࣮ࢫㄏᑟయ 1 (6’-SeMe ࣛࢡࢺ࣮ࢫㄏᑟయ)ࠊཬࡧࠊࢢࣝࢥ࣮ࢫ 6 ఩࣓ࢳࣝࢭࣞࣀᇶ⨨᥮ࣛࢡࢺ࣮ࢫㄏᑟయ 2 (6-SeMe ࣛࢡࢺ࣮ࢫㄏᑟయ)࡜ࠊࡑࢀࡽࡢ࢔ࢢࣜࢥࣥ㒊఩࡟࢔࣑ࣀᇶࢆ᭷ࡍࡿ࣮ࣜࣥ࢝ࢆᑟ ධࡋࡓSPR ヨ㦂᫬࡟ࢭࣥࢧ࣮ࢳࢵࣉ࡬ᅛᐃ໬ࡍࡿࡓࡵࡢ໬ྜ≀ 3ࠊཬࡧࠊ໬ྜ≀ 4 ࡜タᐃ ࡋࡓ (Figure 5)ࠋ

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- 10 - Figure 5 ࡲࡎࠊ6’-SeMe ࣛࢡࢺ࣮ࢫㄏᑟయ 1 ཬࡧ 3 ࡢྜᡂࢆ┠ᣦࡍࡇ࡜࡜ࡋࠊ㏫ྜᡂゎᯒࢆ⾜ࡗࡓ (Scheme 1)ࠋ Scheme 1 ௒ᚋࡢࡼࡾ኱ࡁ࡞ࢭࣞࣀ⢾㙐ྜᡂࢆど㔝࡟ධࢀࡓ㝿࡟ࠊ཰⋡ࡀᮍ▱ࡢࢭࣞࣥᑟධ཯ᛂࢆࠊ ࢜ࣜࢦ⢾ᵓ⠏ᚋ࡟⾜࠺ࡇ࡜ࡣྜᡂୖࣜࢫࢡࡀ㧗࠸࡜⪃࠼ࡽࢀࡓࠋࡑࡇ࡛ࠊ༢⢾ࡢẁ㝵࡛ࢭ ࣞࣥཎᏊᑟධࢆ⾜࠺ࡇ࡜࡜ࡋࠊMeSe ᇶࢆ᭷ࡍࡿ࢞ࣛࢡࢺ࣮ࢫ౪୚య 8 ࢆタィࡋࡓࠋ౪୚య 8 ࡣࠊࢢࣝࢥ࣮ࢫཷᐜయ 9 ࡜ࡢࢢࣜࢥࢩࣝ໬ࢆ⾜࠸ࢭࣞࣀࣛࢡࢺ࣮ࢫ 7 ࡬࡜ㄏᑟᚋࠊ୍㒊ࡣ ࢔ࢩࣝ⣔ಖㆤᇶࡢ⬺ಖㆤࢆ⾜࠸ඹ⤖ᬗ໬⏝ࡢ⢾㙐 1 ࡬࡜ㄏᑟࡋࠊṧࡾࡢ㒊ศࡣࢫ࣮࣌ࢧ࣮ ࡜࡞ࡿ࢔࣑ࣀ࢚ࢺ࢟ࢩ࢚ࢱࣀ࣮ࣝࡢTFAc ಖㆤయ12㸦໬ྜ≀ 5㸧ࢆᑟධࡋࡓᚋ࡟⬺ಖㆤࢆ⾜ ࠸⤖ྜヨ㦂⏝ࡢ⢾㙐3 ࢆྜᡂࡍࡿࡇ࡜࡜ࡋࡓࠋ ⥆࠸࡚ࠊྛྜᡂࣘࢽࢵࢺࡢಖㆤᵝᘧ࡟ࡘ࠸࡚㏙࡭ࡿࠋࢭࣞࣥཎᏊࡣ◲㯤ཎᏊ࡜ྠᵝ࡟ࣃ

12_{Y. J. Kwon, S. M. Standley, A. P. Goodwin, E. R. Gillies, J. M. J. Frechet, Mol. Pharmaceutics} 2005, 2, 83-91.

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ࣛࢪ࣒࢘࡬ࡢᙉ࠸㓄఩ຊࢆ᭷ࡍࡿࡓࡵࠊ᥋ゐỈ⣲ῧຍἲ࡟ࡼࡿBn ᇶࡢ⬺ಖㆤࡀ୙ྍ⬟࡜࡞ ࡿ13ࠋࡑࡢࡓࡵࠊᮏ◊✲࡛ࡣ㐟㞳Ỉ㓟ᇶࡢಖㆤ࡟Bn ᇶࢆ⏝࠸࡞࠸ྜᡂィ⏬࡜ࡋࡓࠋ ࢞ࣛࢡࢺ࣮ࢫ౪୚య࡛ࡣࠊࢢࣜࢥࢩࢻ⤖ྜᙧᡂ᫬ࡢ㞄᥋ᇶ㛵୚ࢆᮇᚅࡋ2 ఩Ỉ㓟ᇶࡣ Bz ᇶ࡛ಖㆤࡋࠊ3 ఩ཬࡧ 4 ఩Ỉ㓟ᇶ࡟ࡣ⬺ಖㆤࢆ⪃៖ࡋ࡚࢚ࢫࢸࣝ⣔ࡢಖㆤᇶ࡛ಖㆤࡍࡿࡇ࡜ ࡜ࡋࡓࠋࡲࡓࠊ࢔ࣀ࣐࣮఩ࡣ⬺㞳ᇶ࡬ࡢㄏᑟࢆ⾜࠺ࡓࡵࠊ㓟ᛶ᮲௳࡛㑅ᢥⓗ⬺ಖㆤࡀྍ⬟ ࡞SE ᇶ࡛ಖㆤࡍࡿࡇ࡜࡜ࡋࡓࠋࢢࣜࢥࢩࣝ໬ࡢ㝿ࡢ⬺㞳ᇶ࡟ࡘ࠸࡚ࡣࠊᚋ㏙ࡍࡿࡀࠊࢭࣞ ࣥཎᏊᏑᅾୗ࡛ྠ᪘ࡢ◲㯤ཎᏊࡢ㑅ᢥⓗάᛶ໬ࡀᅔ㞴࡛࠶ࡿࡇ࡜ࡀ⪃࠼ࡽࢀࡓࡓࡵࠊࣇࢵ ⣲ࡲࡓࡣࢺࣜࢡࣟࣟ࢔ࢭࢺ࢖࣑ࢹ࣮ࢺ౪୚యࢆ⏝࠸ࡿィ⏬࡜ࡋࡓࠋ ࢢࣝࢥ࣮ࢫཷᐜయ࡛ࡣࠊ๓㏙ࡢ⌮⏤࡟ࡼࡾBn ᇶࢆ⏝࠸ࡿࡇ࡜ࡀ࡛ࡁ࡞࠸ࡓࡵࠊ࢔ࢩࣝ⣔ ಖㆤᇶࡢ୰࡛❧య㞀ᐖࡢᑠࡉ࠸Ac ᇶ࡛Ỉ㓟ᇶࢆಖㆤࡍࡿࡇ࡜࡜ࡋࡓࠋࡲࡓࠊࢢࣝࢥ࣮ࢫཷ ᐜయ࡛ࡶࠊ࢔ࣀ࣐࣮఩࡟㓟ᛶ᮲௳࡛⬺ಖㆤྍ⬟࡞SE ᇶࢆᑟධࡋࠊ࣮ࣜࣥ࢝ᑟධࡢ㝿ࡢࢢࣜ ࢥࢩࣝ౪୚య࡬ࡢኚ᥮ࢆ⪃៖ࡍࡿࡇ࡜࡜ࡋࡓࠋࡇࡢࢢࣝࢥ࣮ࢫࢺࣜ࢔ࢭࢳࣝཷᐜయ 9 ࡣᙜ ◊✲ᐊ࡛ࠊࡍ࡛࡟⦰ྜ཯ᛂ࡟࠾ࡅࡿ᭷⏝ᛶࡀ☜ㄆࡉࢀ࡚࠸ࡿ14ࠋ ᭱ᚋ࡟ࠊ࣮ࣜࣥ࢝ࡢ๓㥑య࡛࠶ࡿ࢔࣑ࣀ࢚ࢺ࢟ࢩ࢚ࢱࣀ࣮ࣝࡢ࢔࣑ࣀᇶࡢಖㆤ࡟ࡘ࠸࡚ ࡣࠊ୍ẁ㝵࡛⢾㙐ࡢ࢔ࢩࣝ⣔ಖㆤᇶ࡜ྠ᫬࡟⬺ಖㆤྍ⬟࡞TFAc ᇶࢆ㑅ᢥࡍࡿࡇ࡜࡜ࡋࡓࠋ ⥆࠸࡚ࠊ㘽࡜࡞ࡿ୍⣭Ỉ㓟ᇶ࡬ࡢࢭࣞࣥࡢᑟධἲ࡟ࡘ࠸࡚ࡔࡀࠊᙜ◊✲ᐊࡢẟཷ15ࡀ㛤Ⓨ ࡋࡓࠊ⤖ᬗ໬࡟ࡼࡿ⢭〇ࡀྍ⬟࡞ࢭࣞࣀࢺࣝ࢜࢖ࣝ㓟↓Ỉ≀11 ࢆ஧⣭࢔࣑ࣥ࡟ࡼࡗ࡚άᛶ ໬ࡋ཯ᛂ࡟⏝࠸ࡿࢭࣞࣥᑟධἲࢆ᥇⏝ࡍࡿࡇ࡜࡜ࡋࡓ (Scheme 2)ࠋ Scheme 2 ࢭࣞࣀࢺࣝ࢜࢖ࣝ㓟↓Ỉ≀11 ࡣࠊḟࡢ཯ᛂᶵᵓ࡟ἢࡗ࡚ồ㟁Ꮚ๣࡜཯ᛂࡋࠊⅣ⣲-ࢭࣞࣥ 13_{Ἑྜ⏤⨾Ꮚ,}_{ᒱ㜧኱Ꮫ኱Ꮫ㝔ᕤᏛ◊✲⛉ಟኈㄽᩥ 2007.} 14_{⋢஭⚽ᶞ,}_{ᒱ㜧኱Ꮫ኱Ꮫ㝔ᕤᏛ◊✲⛉ಟኈㄽᩥ 2009.} 15_{a) ẟཷ㞞඾,}_{ᒱ㜧኱Ꮫ኱Ꮫ㝔ᕤᏛ◊✲⛉ಟኈㄽᩥ 2010. b) H. Ishihara, S. Sato, Y.}

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- 12 - ⤖ྜࢆᙧᡂࡍࡿࠋ໬ྜ≀11 ࡢ࢝ࣝ࣎ࢽࣝⅣ⣲ࡀồ᰾๣㸦஧⣭࢔࣑ࣥ㸧࡟ࡼࡾᨷᧁࡉࢀࡿࡇ ࡜࡛ࢭࣞࣀࢺࣝ࢜࢖ࣝ㓟ࡀ⬺㞳ࡋࠊሷᇶࡢᏑᅾୗ࡛⏕ᡂࡋࡓࢭࣞࣀ࣮ࣛࢺ࢔ࢽ࢜ࣥࡀ⬺㞳 ᇶࢆᣢࡘⅣ⣲ࢆᨷᧁࠊ❧యࡢ཯㌿ࢆక࠸࡞ࡀࡽⅣ⣲-ࢭࣞࣥ⤖ྜࢆ᪂ࡓ࡟ᙧᡂࡉࡏࡿ (Scheme 3)ࠋ Scheme 3 ཯ᛂ୰࡟Ⓨ⏕ࡍࡿࢭࣞࣀ࣮ࣛࢺ࢔ࢽ࢜ࣥࡣࠊሷᇶ࡜㓟⣲ࡢᏑᅾୗ࡛ᐜ᫆࡟ࢪࢭࣞࢽࢻ16࡬ ࡜ศゎࡍࡿࡓࡵࠊ4 ⣭࢔ࣥࣔࢽ࣒࢘ሷࡢᙧ࡛Ᏻᐃ໬ࡉࡏࡿࡓࡵ࡟ DIEA ࢆ⏝࠸ࡿᚲせࡀ࠶ࡿ (Scheme 4)ࠋ Scheme 4 ḟ࡟ࠊࢢࣝࢥ࣮ࢫ 6 ఩ࢭࣞࣥ⨨᥮ᆺ࡛࠶ࡿ 6 ࢭࣞࣀࣛࢡࢺ࣮ࢫㄏᑟయ 2 ࡢྜᡂᡓ␎࡟ࡘ ࠸࡚ࡔࡀࠊ6’-ࢭࣞࣀࣛࢡࢺ࣮ࢫㄏᑟయ 1 ࡢྜᡂ࡛ᚓࡽࢀࡿ᝟ሗࢆࡶ࡜࡟タィࡍࡿࡇ࡜࡜ࡋࠊ ヲ⣽࡟ࡘ࠸࡚ࡣ➨3 ❶࡛ᚋ㏙ࡍࡿࡇ࡜࡜ࡋࡓࠋ

16_{MARCH’S Advanced Organic Chemistry Reaction, Mechanisms, and Structure 5}th_{edition; M. B.}

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➨ ➨㸰❶ 6’ࢭࣞࣀࣛࢡࢺ࣮ࢫࡢྜᡂ ➨㸯⠇ ࢭࣞࣀ࢞ࣛࢡࢺ࣮ࢫ౪୚యࡢྜᡂ ࢔ࣀ࣐࣮఩ࢆSE ᇶ࡛ಖㆤࡋࠊ2,3 ఩ࢆ࣋ࣥࢰ࢖ࣝᇶ࡛ࠊ4 ఩ࢆ࢔ࢭࢳࣝᇶ࡛ಖㆤࡋࡓ 6-ࢭࣞࣀ࢞ࣛࢡࢺ࣮ࢫ౪୚యࡢྜᡂࢆ⾜ࡗࡓ (Scheme 5)ࠋ Scheme 5 ᕷ㈍ࡢE-D-galactose-pentaacetate 㸦໬ྜ≀ 13㸧ࢆฟⓎཎᩱ࡜ࡋ࡚ࠊᐃἲ࡟ࡼࡾ࢔ࣀ࣐࣮఩ ࢆ SE ᇶ࡟࡚ಖㆤࡋࠊࢩࣜ࢝ࢤ࣒ࣝ࢝ࣛࢡ࣐ࣟࢺࢢࣛࣇ࢕࣮࡟࡚ヨ⸆ࡢࡳࢆ㝖࠸ࡓᚋࠊAc ᇶࢆ⬺ಖㆤࡋࠊEtOH / n-hexane ࡟࡚⤖ᬗ໬ࢆ⾜࠸୕ẁ㝵ࠊ཰⋡ 69%࡟࡚໬ྜ≀ 15 ࢆᚓࡓࠋ ໬ྜ≀15 ࡢ 4,6 ఩Ỉ㓟ᇶࡢ࣋ࣥࢪࣜࢹࣥ໬ࠊ2,3 ఩Ỉ㓟ᇶࡢ࣋ࣥࢰ࢖ࣝ໬ࠊ⬺࣋ࣥࢪࣜࢹࣥ ໬ࢆ㐃⥆ⓗ࡟⾜࠸ࠊ⤖ᬗ໬ (AcOEt / n-Hexane)࡟ࡼࡿ༢㞳࡛ࠊ୕ẁ㝵཰⋡ 48%࡟࡚໬ྜ≀ 16 ࢆᚓࡓࠋࡑࡢᚋࠊ࢔ࢵ࣌ࣝ཯ᛂࢆ⏝࠸࡚໬ྜ≀22 ࡢ㐟㞳࡜࡞ࡗࡓ୍⣭ࡢ 6 ఩Ỉ㓟ᇶࢆࠊ㑅 ᢥⓗ࡟Br ࡛⨨᥮ࡋ཰⋡ 87%࡛໬ྜ≀ 17 ࢆᚓࡿࡇ࡜ࡀ࡛ࡁࡓࠋ ⥆࠸࡚ࢭࣞࣥᑟධヨ⸆࡛࠶ࡿࢭࣞࣀࢺࣝ࢜࢖ࣝ㓟↓Ỉ≀11 ࡢྜᡂࢆ⾜ࡗࡓ (Scheme 6)ࠋ 㔠ᒓࢭࣞࣥࡢỈ⣲໬࣍࢘⣲ࢼࢺ࣒ࣜ࢘࡟ࡼࡿ㑏ඖ࡟⥆࠸࡚ࠊp-methylbenzoyl chloride ࡟ࡼࡿ ࢭࣞࣥཎᏊࡢࢺࣝ࢜࢖ࣝ໬ࠊ᭱ᚋ࡟ࣚ࢘⣲ࡢࣇ࣮ࣜࣛࢪ࢝ࣝ࡟ࡼࡿࢭࣞࣥࡢ㓟໬ࢆ⾜࠸ࠊ ⤖ᬗ໬ (CH2Cl2 / n-hexane)࡟ࡼࡾ཰⋡ 56%㸦୕ẁ㝵㸧࡟࡚ࢭࣞࣀࢺࣝ࢜࢖ࣝ㓟ࢪࢭࣞࢽࢻ 18 ࢆᚓࡓࠋ⥆࠸࡚໬ྜ≀18 ࢆளࣜࣥ㓟ࢺ࢚ࣜࢳ࡛ࣝ㑏ඖࡋࠊ⤖ᬗ໬ (diethylether / n-hexane) ࡟࡚ࠊࢭࣞࣀ࢝ࣝ࣎ࣥ㓟↓Ỉ≀11 ࢆ཰⋡ 90%࡛ᚓࡓࠋ

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- 14 - Scheme 6 ㄪ〇ࡋࡓࢭࣞࣀࢺࣝ࢜࢖ࣝ㓟↓Ỉ≀11 ࡜ Br య 17 ࡟ piperidineࠊDIEA ࢆ཯ᛂࡉࡏࡿࡇ࡜ ࡛ࠊᐃ㔞ⓗ࡟໬ྜ≀18 ࢆᚓࡿࡇ࡜ࡀ࡛ࡁࡓࠋࡑࡢᚋࠊ㐟㞳ࡢ 4 ఩Ỉ㓟ᇶࢆ Ac ᇶ࡛ಖㆤࡋ ࡓᚋ࡟ࠊTol ᇶ࠿ࡽ Me ᇶ࡬ࡢኚ᥮ࢆ⾜࠸཰⋡ 78%࡟࡚໬ྜ≀ 20 ࢆᚓࡓࠋࡲࡓࠊࡇࡢ཯ᛂ࡛ ࡣ๪⏕ᡂ≀࡜ࡋ࡚ࠊࢪࢭࣞࢽࢻయ21 ࡀᚓࡽࢀࡓࠋࡑࡢᚋࠊ໬ྜ≀ 20 ࡢ SE ᇶࢆ⬺ಖㆤࡋ࣊ ࣑࢔ࢭࢱ࣮ࣝయ22 ࡬࡜ㄏᑟࡋࡓᚋࠊᐃἲ࡟ᚑࡗ࡚ࣇࢵ⣲౪୚య 23 ࢆ 97%ࡢ཰⋡࡛ࠊࢺࣜ ࢡࣟࣟ࢔ࢭࢺ࢖࣑ࢹ࣮ࢺ౪୚య24 ࢆᐃ㔞ⓗ࡟ᚓࡿࡇ࡜ࡀ࡛ࡁࡓ (Scheme 7)ࠋ Scheme 7

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➨ ➨㸰⠇ 6’ࢭࣞࣀࣛࢡࢺ࣮ࢫࡢྜᡂ ㄪ〇ࡋࡓࣇࢵ⣲౪୚య23ࠊࢺࣜࢡࣟࣟ࢔ࢭࢺ࢖࣑ࢹ࣮ࢺ౪୚య 24 ࡜ẚ㍑ࡢࡓࡵ࡟ู㏵ྜ ᡂࡋࡓࣇ࢙ࢽࣝࢳ࢜ࢢࣜࢥࢩࢻ౪୚య25 ࢆ⏝࠸࡚⦰ྜ཯ᛂࢆ⾜ࡗࡓࠋཷᐜయ࡟ࡣࢺࣜ࢔ࢭ ࢳࣝࢢࣝࢥ࣮ࢫཷᐜయ9 ࢆ⏝࠸ࡓ (Table 1)ࠋ Table 1 Entry 1 ࡛ࡣ PhS ౪୚య 25 ࡟ࠊNISࠊTfOH ࢆస⏝ࡉࡏ཯ᛂࢆ⾜ࡗࡓࡀࠊPhS ᇶࡢάᛶ໬ࡣ ㉳ࡇࡽࡎ┠ⓗ໬ྜ≀ࢆᚓࡿࡇ࡜ࡣ࡛ࡁ࡞࠿ࡗࡓ17ࠋࡲࡓࠊᚓࡽࢀࡓࡶࡢࡣࠊ໬ྜ≀ 25 ࡢศ ゎ≀࡜ᮍ཯ᛂࡢཷᐜయࡔࡅ࡛࠶ࡗࡓࠋEntry 2 ࡛ࡣࣇࢵ⣲౪୚య 23 ࢆࠊCp2ZrCl2࡜ AgOTf ࡟ࡼࡾάᛶ໬ࡋࡓࡀࠊ┠ⓗࡢ⦰ྜ≀ࡣ⑞㊧㔞⛬ᗘࡋ࠿☜ㄆ࡛ࡁࡎࠊ࣑࣊࢔ࢭࢱ࣮ࣝయ࡜ᮍ ཯ᛂࡢཷᐜయࢆᚓࡿࡢࡳ࡛࠶ࡗࡓ18ࠋEntry 3 ࡛ࡣࢺࣜࢡࣟࣟ࢔ࢭࢺ࢖࣑ࢹ࣮ࢺ౪୚య 24 ࢆࠊ TMSOTf ࡟ࡼࡾάᛶ໬ࡋࡓࡀ࣑࣊࢔ࢭࢱ࣮ࣝయࠊཷᐜయᮍ཯ᛂศ࡜ TMS ໬ࡉࢀࡓཷᐜయࢆ ᚓࡿࡢࡳ࡛࠶ࡗࡓ19ࠋ ௨ୖࡢ⤖ᯝࡼࡾࠊࣇࢵ⣲ཬࡧࢺࣜࢡࣟࣟ࢔ࢭࢺ࢖࣑ࢹ࣮ࢺᇶࢆ⬺㞳ᇶ࡟ᣢࡘࢭࣞࣀ࢞ࣛ ࢡࢺ࣮ࢫ౪୚యࢆ⏝࠸ࡓሙྜࠊ⦰ྜ≀ࡣᚓࡽࢀ࡞࠿ࡗࡓࡀࠊ⬺㞳ᇶࡢάᛶ໬ࡣ㉳ࡇࡾࠊ࣊

17_{a) P. Konradsson, U. E. Udodong, B. Fraser-Reid, Tetrahedron Lett. 1990, 31, 4313-4316; b) P.}

Konradsson, D. R. Mootoo, R. E. McDevitt, B. Fraser-Reid, J. Chem. Soc. Chem. Commun. 1990, 270–272; c) G. H. Veeneman, S. H. Van Leeuwen, J. H. Van Boom, Tetrahedron Lett. 1990, 31, 1331-1334.

18_{K. Suzuki, H. Maeta, T. Suzuki, T. Matsumoto, Tetrahedron Lett. 1989, 30, 6879-6882.}

19_{a) R. R. Schmidt, J. Michel, Angew. Chem. Int. Ed. Engl. 1980, 19, 731̽732; b) R. R. Schmidt,}

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࣑࢔ࢭࢱ࣮ࣝయࢆ୚࠼ࡿࡇ࡜ࡀศ࠿ࡗࡓࠋࡇࡢࡇ࡜ࡣࠊࢢࣝࢥ࣮ࢫࢺࣜ࢔ࢭࢳࣝཷᐜయ 9

ࡢప཯ᛂᛶࡀཎᅉ࡜⪃࠼ࡽࢀࡓࡓࡵࠊ㧗཯ᛂᛶࢢࣝࢥ࣮ࢫཷᐜయࡢࣔࢹࣝ࡜ࡋ࡚ࠊᕷ㈍ࡢ methyl 2,3,4-tri-O-benzyl-D-D-glucopyranoside 㸦໬ྜ≀ 26㸧ࢆ⏝࠸࡚⦰ྜ཯ᛂࡢ᳨ウࢆ⾜࠺ࡇ ࡜࡜ࡋࡓ (Table 2)ࠋ Table 2 Entry 1 ࡛ࡣࠊTable 1 ࡢ⤖ᯝࡼࡾάᛶ໬ࡀ㉳ࡁ࡙ࡽ࠸ࡇ࡜ࡀ⪃࠼ࡽࢀࡓࡓࡵヨ⸆ࡢ➼㔞ࢆ ቑࡸࡋࠊ཯ᛂ ᗘࡶ㧗ࡃࡋ࡚཯ᛂࢆ⾜ࡗࡓࡀࠊ┠ⓗࡢ⦰ྜ≀ࢆᚓࡿࡇ࡜ࡣ࡛ࡁ࡞࠿ࡗࡓࠋ ࡇࡢ཯ᛂ࡛ࡣࠊࢭࣞࣀ࢟ࢩࢻయ28 ࢆΰྜ≀࡜ࡋ࡚ᚓࡓࠋࡇࡢࢭࣞࣀ࢟ࢩࢻయࡣࠊ཯ᛂ⣔୰ ࡛ࣚ࢘⣲࢝ࢳ࢜ࣥࡀࢭࣞࣥཎᏊ࡟㓄఩ࡋࡓᚋ࡟ࠊ㓟໬ࢆཷࡅ࡚⏕ᡂࡋࡓ࡜⪃࠼ࡽࢀࡿࡓࡵ (Scheme 8)ࠊࢭࣞࣥཎᏊᏑᅾୗ࡟࠾ࡅࡿ PhS ᇶࡢάᛶ໬ࡀᅔ㞴࡛࠶ࡿࡇ࡜ࢆᙉࡃ♧၀ࡋ࡚࠸ ࡿࠋࡋ࠿ࡋ࡞ࡀࡽࠊࢭࣞࣀ࢟ࢩࢻయ28 ࡣ୙Ᏻᐃ࡛࠶ࡾ༢㞳࡟ࡣ⮳ࡽ࡞࠿ࡗࡓࠋ Scheme 8 Entry 2 ࡛ࡶࠊάᛶ໬ࡀ㉳ࡁ࡙ࡽ࠸ࡇ࡜ࡀ⪃࠼ࡽࢀࡓࡓࡵ ᗘࢆୖࡆ࡚཯ᛂࢆ⾜ࡗࡓࠋ⤖ ᯝ࡜ࡋ࡚ࠊ཰⋡53%࡛ࠊ⦰ྜ≀ 27 ࢆᚓࡿࡇ࡜ࡀ࡛ࡁࡓࠋࡲࡓࠊ27 ࡢ௚࡟ࡣ࣑࣊࢔ࢭࢱ࣮ࣝ య࡜ཷᐜయࡢᮍ཯ᛂศ࡜ࢆᅇ཰ࡋࡓࠋ୍᪉ࠊࢺࣜࢡࣟࣟ࢔ࢭࢺ࢖࣑ࢹ࣮ࢺ౪୚యࢆ⏝࠸ࡓ

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Entry 3 ࡛ࡣࠊ໬ྜ≀ 27 ࢆ 66%ࡢ཰⋡࡛ᚓࡿࡇ࡜ࡀ࡛ࡁࡓࠋ๪⏕ᡂ≀࡜ࡋ࡚ࠊ࣑࣊࢔ࢭࢱ࣮ ࣝయࠊN-ࢢࣜࢥࢩࢻࠊTMS ໬ࡉࢀࡓཷᐜయࢆᚓࡓࠋ௨ୖࡢ⤖ᯝ࠿ࡽࠊMeSe ᇶࡢᏑᅾୗ࡛ PhS ᇶࢆ౪୚యࡢ⬺㞳ᇶ࡜ࡋ࡚⏝࠸ࡿࡇ࡜ࡣᅔ㞴࡛࠶ࡿࡀࠊࣇࢵ⣲ཬࡧࢺࣜࢡࣟࣟ࢔ࢭࢺ࢖ ࣑ࢹ࣮ࢺᇶࢆ⬺㞳ᇶ࡜ࡋ࡚⏝࠸ࡿࡇ࡜࡟ࡼࡾࢢࣜࢥࢩࣝ໬ࡀྍ⬟࡛࠶ࡿࡇ࡜ࡀࢃ࠿ࡗࡓࠋ ࡲࡓࠊTable 1 ࡜ Table 2 ࡢ⤖ᯝࡣࠊࢢࣝࢥ࣮ࢫࢺࣜ࢔ࢭࢳࣝཷᐜయ 9 ࡢప཯ᛂᛶࢆ♧ࡋࡓࠋ ࡑࡇ࡛ࠊࢢࣜࢥࢩࣝ໬ࡢ཰⋡ྥୖࢆ┠ⓗ࡟ࠊ㟁Ꮚ౪୚ᛶ࡛࠶ࡾࠊୟࡘࠊ㓟ᛶ᮲௳࡟ࡼࡿ㑅 ᢥⓗ⬺ಖㆤࡀྍ⬟࡞MPM ᇶࢆ 2ࠊ3 ఩࡟ᑟධࡋࡓ᪂ࡋ࠸ࢢࣝࢥ࣮ࢫཷᐜయ 31 ࢆタィࡋࡓ (Scheme 9)ࠋ Scheme 9 ࢢࣝࢥ࣮ࢫࡢ4,6-Bzld ಖㆤయ20_㸦໬ྜ≀_{29㸧ࢆฟⓎ≀㉁࡜ࡋ࡚ࠊ2,3 ఩ࢆ MPM ᇶ࡛ಖㆤ} ࡋࡓᚋ࡟ࠊBzld ᇶࢆ⬺ಖㆤࡋ࡚ࠊ஧ẁ㝵཰⋡ 64%࡟࡚໬ྜ≀ 30 ࢆᚓࡓࠋࡑࡢᚋࠊ6 ఩ࢆ㑅 ᢥⓗ࡟Ac ᇶ࡛ಖㆤࡋࠊ┠ⓗࡢࢢࣝࢥ࣮ࢫཷᐜయ 31 ࢆ཰⋡ 80%࡟࡚ྜᡂࡋࡓࠋࡇࡢ᪂ࡋ࠸ ࢢࣝࢥ࣮ࢫཷᐜయࢆ⏝࠸࡚ࠊTable 2 ࡟࠾࠸࡚᭱ࡶ཰⋡ࡢ㧗࠿ࡗࡓࢺࣜࢡࣟࣟ࢔ࢭࢺ࢖࣑ࢹ ࣮ࢺᇶࢆᣢࡘࢭࣞࣀ࢞ࣛࢡࢺ࣮ࢫ౪୚య24 ࡜ࡢ⦰ྜ཯ᛂࢆ⾜ࡗࡓ (Scheme 10)ࠋ Scheme 10 ཯ᛂࡢ⤖ᯝࠊ┠ⓗ࡜ࡍࡿ6’-MeSe ࣛࢡࢺ࣮ࢫㄏᑟయ 32 ࢆ 71%ࡢ཰⋡࡛ྜᡂࡍࡿࡇ࡜ࡀ࡛ ࡁࡓࠋ๪⏕ᡂ≀࡜ࡋ࡚ࡣ࣑࣊࢔ࢭࢱ࣮ࣝయ࡜ࠊཷᐜయࡢTMS ໬యࢆᚓ࡚ࠊࡲࡓཷᐜయࡢᮍ ཯ᛂศࡶᅇ཰ࡋࡓࠋࡲࡓࠊMPM ᇶࡢ୍ࡘࡀࣝ࢖ࢫ㓟࡟ࡼࡾ⬺ಖㆤࡉࢀࡓ஧⢾ࡀ㉁㔞ศᯒ࡟

20_{K. Jansson, S. Ahlfors, T. Frejd, J. Kihlberg, G. Magnusson, J. Dahmen, G. Noori, K. Stenvall, J.}

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- 18 - ࡼࡾ☜ㄆࡉࢀࡓࡓࡵ཰⋡ᨵၿ࡟࠾࠸࡚ࡣࠊMPM ᇶࡢ⬺㞳ࢆ᭱ᑠ㝈࡟ᢚไࡍࡿ᮲௳ࡢ☜❧ࡀ ᚲせ࡛࠶ࡿ࡜⪃࠼ࡽࢀࡿࠋ ⥆࠸࡚ᚓࡽࢀࡓ6’-ࢭࣞࣀࣛࢡࢺ࣮ࢫㄏᑟయ 32 ࠿ࡽࠊ┠ⓗ໬ྜ≀ 1 ࡬ࡢㄏᑟ࡜ࠊ࣮ࣜࣥ࢝ ࡢᑟධ࡟ྥࡅ࡚஧⢾౪୚య࡬ࡢㄏᑟࢆ⾜ࡗࡓ (Scheme 11)ࠋ Scheme 11 ໬ྜ≀32 ࡢ MPM ᇶࢆ-20 °C ࡟࠾࠸࡚㑅ᢥⓗ࡟㝖ཤࡋࠊ໬ྜ≀ 33 ࢆᚓࡓࠋᚓࡽࢀࡓ໬ྜ ≀33 ࡢ୍㒊ࡣࠊ㉸㡢Ἴ↷ᑕୗ21ࠊຍ⁐፹ศゎ࡟ࡼࡿ࢔ࢩࣝ⣔ಖㆤᇶࡢ㝖ཤࢆ⾜࠸ඹ⤖ᬗ໬ ⏝ࡢ⢾㙐1 ࡬࡜ㄏᑟࡋࡓࠋṧࡾࡢ໬ྜ≀ 33 ࡣ஧⢾౪୚య࡬࡜ㄏᑟࡍࡿࡓࡵࠊࢢࣜࢥࢩࣝ໬ ᫬ࡢ㞄᥋ᇶ㛵୚ࢆᮇᚅࡋ㐟㞳࡜࡞ࡗࡓ2,3 ఩ࡢỈ㓟ᇶ࡟࣋ࣥࢰ࢖ࣝᇶࢆ཰⋡ 91%࡛ᑟධࡋࡓࠋ ࡑࡢᚋࠊᐃἲ࡟ᚑ࠸ࠊ໬ྜ≀35 ࡢ SE ᇶࡢ⬺ಖㆤࠊࢺࣜࢡࣟࣟ࢔ࢭࢺ࢖࣑ࢹ࣮ࢺ໬ࢆ⾜࠸ࠊ 6’-ࢭࣞࣀࣛࢡࢺ࣮ࢫ౪୚య 36 ࡬࡜ㄏᑟࡋࡓࠋ᭱ᚋ࡟࣮ࣜࣥ࢝໬ྜ≀ 5 ࡜ࡢ⦰ྜ཯ᛂ࡟౪ࡋࠊ ཰⋡90%࡛໬ྜ≀ 37 ࢆྜᡂࡋࠊ⥆࠸࡚ࠊ㉸㡢Ἴ↷ᑕୗࠊຍ⁐፹ศゎࢆ⾜࠺ࡇ࡜࡛ SPR ヨ㦂 ⏝ࡢ໬ྜ≀3 ࡢྜᡂࢆ㐩ᡂࡋࡓ (Scheme 12)ࠋ

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- 20 - ➨ ➨㸱❶ 6-ࢭࣞࣀࣛࢡࢺ࣮ࢫࡢྜᡂ ➨㸯⠇ ࢭࣞࣀࢢࣝࢥ࣮ࢫཷᐜయࡢྜᡂ ➨ 2 ❶࡟࠾࠸࡚ࠊᚓࡽࢀࡓ▱ぢࢆඖ࡟ࢢࣝࢥ࣮ࢫࡢ 6 ఩ࢆࢭࣞࣥ⨨᥮ࡋࡓࢢࣝࢥ࣮ࢫཷ ᐜయࢆタィࡍࡿࡇ࡜࡜ࡋࡓࠋࢢࣝࢥ࣮ࢫ 2 ఩࡟ࡣ஧⢾ᵓ⠏ᚋࡢ࢔ࣀ࣐࣮఩࡬ࡢ࣮ࣜࣥ࢝ᑟ ධ᫬࡟ࠊ❧య㑅ᢥⓗ࡟E-ࢢࣜࢥࢩࢻࢆᚓࡿᚲせࡀ࠶ࡿࡓࡵࠊ㞄᥋ᇶ㛵୚ࢆ୚࠼ࡿ࢔ࢩࣝ⣔ಖ ㆤᇶࢆᑟධࡍࡿࡇ࡜ࡀᮃࡲࢀࡓࠋࡋ࠿ࡋ࡞ࡀࡽࠊ࢞ࣛࢡࢺ࣮ࢫ౪୚య࡟ࡼࡿࢢࣜࢥࢩࣝ໬ ᫬࡟㝿ࡋ࡚4 ఩Ỉ㓟ᇶࡢప཯ᛂᛶࡀᠱᛕࡉࢀࡓࡓࡵࠊ㟁Ꮚ౪୚ᛶࡢ MPM ᇶࢆ 2,3 ఩ᇶ࡟ᣢ ࡘ6-ࢭࣞࣀࢢࣝࢥ࣮ࢫཷᐜయ 43 ࢆタィࡋࡓ (Scheme 13)ࠋ Scheme 13 ➨2 ❶࡛⏝࠸ࡓ໬ྜ≀ 30 ࢆฟⓎ≀㉁࡜ࡋ࡚ࠊ6-MeSe ࢞ࣛࢡࢺ࣮ࢫ౪୚యྜᡂ᫬࡜ྠᵝࡢ ⤒㊰࡛ྜᡂࢆ⾜ࡗࡓࠋ໬ྜ≀30 ࡢ 6 ఩ࢆ 96%ࡢ཰⋡࡟࡚ Br ໬ࠊࡑࡢᚋࠊࢭࣞࣀࢺࣝ࢜࢖ ࣝ㓟↓Ỉ≀11 ࢆ⏝࠸࡚ࢺࣝ࢜࢖ࣝࢭࣞࣀ໬ࡋࠊ໬ྜ≀ 39 ࢆ཰⋡ 96%࡛ᚓࡓࠋḟ࡟ࠊ㐟㞳 4 ఩Ỉ㓟ᇶࢆ࢔ࢭࢳࣝᇶ࡛ಖㆤࡋ཰⋡98%࡛໬ྜ≀ 40 ࢆᚓࡓᚋࠊࢺࣝ࢜࢖ࣝᇶࢆ in situ ࢭࣞ ࣀ࣮ࣛࢺ࢔ࢽ࢜ࣥἲࢆ⏝࠸࡚Me ᇶ࡬࡜཰⋡ 89%࡛ኚ᥮ࡋ໬ྜ≀ 41 ࢆᚓࡓࠋࡇࡢ཯ᛂ࡛ࡣ ࢪࢭࣞࢽࢻయ42 ࡶᚓࡓࠋ᭱ᚋ࡟ࠊ໬ྜ≀ 41 ࡢ 4 ఩࢔ࢭࢳࣝᇶࢆ⬺ಖㆤࡋ཰⋡ 87%࡛ 6-ࢭ ࣞࣀࢢࣝࢥ࣮ࢫཷᐜయ43 ࢆྜᡂࡋࡓࠋ

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➨ ➨㸰⠇ 6-ࢭࣞࣀࣛࢡࢺ࣮ࢫࡢᵓ⠏ ➨ 1 ⠇࡟࡚ྜᡂࡋࡓࢭࣞࣀࢢࣝࢥ࣮ࢫཷᐜయ࡜ࠊ⡆౽࡟ㄪ〇ࡍࡿࡇ࡜ࡀྍ⬟࡞࢞ࣛࢡࢺ ࣮ࢫ౪୚య22㸦໬ྜ≀44㸧࡜ࡢ⦰ྜ཯ᛂࢆ⾜ࡗࡓ(Scheme 14)ࠋ Scheme 14 ཯ᛂࡢ⤖ᯝࠊ཰⋡79%࡛┠ⓗࡢ 6-MeSe ࣛࢡࢺ࣮ࢫㄏᑟయ 45 ࢆྜᡂࡍࡿࡇ࡜ࡀ࡛ࡁࡓࠋ ๪⏕ᡂ≀࡜ࡋ࡚ࡣ࣑࣊࢔ࢭࢱ࣮ࣝయ࡜TMS ໬ࡉࢀࡓཷᐜయࢆᚓ࡚ࠊࡲࡓࠊཷᐜయࡢᮍ཯ᛂ ศࡶᅇ཰ࡋࡓࠋ ⥆࠸࡚ᚓࡽࢀࡓ6-ࢭࣞࣀࣛࢡࢺ࣮ࢫㄏᑟయ 45 ࠿ࡽࠊ┠ⓗ໬ྜ≀ 2 ࡬ࡢㄏᑟ࡜ࠊ࣮ࣜࣥ࢝ ࡢᑟධ࡟ྥࡅ࡚஧⢾౪୚య࡬ࡢㄏᑟࢆ⾜ࡗࡓ (Scheme 15)ࠋ Scheme 15 6’-ࢭࣞࣀࣛࢡࢺ࣮ࢫㄏᑟయ 32 ࡢಖㆤᇶኚ᥮࡜ྠᵝ࡟ࠊ໬ྜ≀ 45 ࡢ MPM ᇶࢆ-20 °C ࡟࠾ ࠸࡚㑅ᢥⓗ࡟㝖ཤࡋࠊ୍㒊ࡣࠊ㉸㡢Ἴ↷ᑕୗࠊຍ⁐፹ศゎ࡟ࡼࡾ࢔ࢩࣝ⣔ಖㆤᇶࢆ㝖ཤࡋ

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- 22 - ໬ྜ≀2 ࡬࡜ㄏᑟࡋࡓࠋ໬ྜ≀ 46 ࡢṧࡾࡣ㐟㞳࡜࡞ࡗࡓ 2,3 ఩ࡢỈ㓟ᇶ࡟཰⋡ 91%࡛࣋ࣥ ࢰ࢖ࣝᇶࢆᑟධࡋࡓࠋࡑࡢᚋࠊᐃἲ࡟ᚑ࠸໬ྜ≀47 ࡢ SE ᇶࢆ⬺ಖㆤࡋࠊ㐟㞳࡜࡞ࡗࡓỈ 㓟ᇶࡢࢺࣜࢡࣟࣟ࢔ࢭࢺ࢖࣑ࢹ࣮ࢺ໬ࢆ⾜࠸ࠊ6-ࢭࣞࣀࣛࢡࢺ࣮ࢫ౪୚య 49 ࡬࡜ㄏᑟࡋࡓࠋ Scheme 16 ⥆࠸࡚ࠊ໬ྜ≀49 ࡜ࠊ࣮ࣜࣥ࢝໬ྜ≀ 5 ࡜ࡢ⦰ྜ཯ᛂࢆ⾜࠸ࠊ཰⋡ 66%࡛໬ྜ≀ 50 ࢆ ᚓࡓ (Scheme 16)ࠋࡑࡢᚋࠊ㉸㡢Ἴ↷ᑕୗࠊຍ⁐፹ศゎ࡟ࡼࡾ࢔ࢩࣝᇶࡢ⬺ಖㆤࢆ⾜࠸ࠊ┠ ⓗ໬ྜ≀4 ࡢྜᡂࢆ㐩ᡂࡋࡓࠋ

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➨ ➨㸲❶ SPR ἲ࡟ࡼࡿࣄࢺ࢞ࣞࢡࢳࣥ-9 NCRD ࡜ࡢ⤖ྜヨ㦂 ➨2 ❶ࠊ➨ 3 ❶࡟࠾࠸࡚ྜᡂࡋࡓ࣮ࣜࣥ࢝ᮎ➃࡟࢔࣑ࣀᇶࢆ᭷ࡍࡿ஧✀㢮ࡢࢭࣞࣀࣛࢡ ࢺ࣮ࢫㄏᑟయ3ࠊ4 ࡜࣏ࢪࢸ࢕ࣈࢥࣥࢺ࣮ࣟࣝ࡜ࡋ࡚ᮍᶆ㆑ࡢࣛࢡࢺ࣮ࢫ࡟࣮ࣜࣥ࢝ࢆᑟධ ࡋࡓࡶࡢࢆ⏝࠸࡚SPR ἲ࡟ࡼࡿ⤖ྜヨ㦂ࢆ⾜࠺ࡇ࡜࡜ࡋࡓࠋ ᐃࡢ㝿ࡢࢭࣥࢧ࣮ࢳࢵࣉ࡟ ࡣࠊ㔠⭷ୖ࡟ࢹ࢟ࢫࢺࣛࣥࢆ௓ࡋ⤖ྜ⏝ࡢᐁ⬟ᇶ࡜ࡋ࡚࢝ࣝ࣎࢟ࢩᇶࢆ᭷ࡍࡿࢭࣥࢧ࣮ࢳ ࢵࣉCM5 ࢆ㑅ᢥࡋࠊࣜ࢞ࣥࢻ࡜࡞ࡿࣛࢡࢺ࣮ࢫㄏᑟయ୕✀㢮ࡑࢀࡒࢀࢆ࢔࣑ࢻ⤖ྜ࡟ࡼࡗ ࡚ᅛᐃ໬ࡋࡓ (Figure 5)ࠋ Figure5 ศᯒᑐ㇟࡜ࡋ࡚ࣄࢺ࢞ࣞࢡࢳࣥ-9 NCRD ࢆ⏝࠸࡚ࠊ5 PM, 10PM, 50 PM, 100 PM, 200 PM ࡢ஬ẁ㝵ࡢ⃰ᗘ࡟タᐃࡋࠊࡑࢀࡒࢀࡢࣛࢡࢺ࣮ࢫࢆࣜ࢞ࣥࢻ࡜ࡋ࡚ᅛᐃ໬ࡋࡓࢭࣥࢧ࣮ࢳ ࢵࣉࢆ⏝࠸࡚ゎᯒࢆ⾜ࡗࡓࠋ࣏ࢪࢸ࢕ࣈࢥࣥࢺ࣮࡛ࣟࣝ࠶ࡿᮍᶆ㆑ࣛࢡࢺ࣮ࢫ࡛ࡣࠊKd = 400 ± 70 PM ࡜࠸࠺⤖ᯝࢆ୚࠼ࡓࠋࡲࡓࠊ6-࣓ࢳࣝࢭࣞࣀࣛࢡࢺ࣮ࢫ࡛ࡣ Kd = 300 ± 70 PM ࡜࠸࠺⤖ᯝࢆ୚࠼࡚ࠊᮍᶆ㆑ࣛࢡࢺ࣮ࢫ࡜ྠ⛬ᗘࡢゎ㞳ᐃᩘࢆᣢࡘࡇ࡜ࡀศ࠿ࡗࡓࠋᖹᯘ ࡽ23࡟ࡼࡿࣇࣟࣥࢱࣝ࢔ࣇ࢕ࢽࢸ࢕࣮ࢡ࣐ࣟࢺࢢࣛࣇ࢕࣮ (FAC)ࢆ⏝࠸ࡓࣄࢺ࢞ࣞࢡࢳࣥ

23_{J. Hirabayashi, T. Hashidate, Y. Arata, N. Nishi, T. Nakamura, M. Hirashima, T. Urashima, T. Oka,}

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- 24 - -9 NCRD ࡜ࣛࢡࢺ࣮ࢫࡢゎ㞳ᐃᩘ ᐃࡢ⤖ᯝࡀ Kd = 103 PM ࡛࠶ࡿࡇ࡜࡜ࠊ୍⯡࡟ࣞࢡࢳࣥ ࡜⢾ࡢㄆ㆑࡟ࡣࡑࢀ࡯࡝ᙉ࠸⤖ྜࢆᚲせ࡜ࡏࡎKdࡣ10㹼1000 PM ⛬ᗘ࡜࠸࠺ࡇ࡜࠿ࡽࠊ௒ ᅇࡢᕪࡣඃ఩࡞ᕪ࡛ࡣ࡞ࡃ࠶ࡃࡲ࡛ྠ⛬ᗘࡢᙉࡉ࡛ㄆ㆑ࡉࢀࡓࡶࡢ࡜⤖ㄽ࡙ࡅࡓࠋ୍᪉ࠊ 6’-࣓ࢳࣝࢭࣞࣀࣛࢡࢺ࣮ࢫ࡛ࡣࠊ࠸ࡎࢀࡢ ᐃ⃰ᗘ࡛ࡶ⤖ྜࢆ⾲ࡍ᭤⥺ࡣᚓࡽࢀࡎࠊ┦஫స ⏝ࢆ♧ࡉ࡞࠸ࡇ࡜ࡀࢃ࠿ࡗࡓࠋ௨ୖࡢࡇ࡜࠿ࡽࠊ➨1 ❶࡛᝿ᐃࡋ࡚࠸ࡓ࡜࠾ࡾࠊࣛࢡࢺ࣮ ࢫࡢ6’఩Ỉ㓟ᇶࡣ࢞ࣞࢡࢳࣥ-9 ࡀࣛࢡࢺ࣮ࢫࢆㄆ㆑ࡍࡿ㝿ࡢ㔜せ࡞Ỉ㓟ᇶ࡛࠶ࡾࠊࡇࡢ఩ ⨨ࢆࢭࣞࣥᶆ㆑ࡋࡓࡇ࡜࡟ࡼࡾㄆ㆑ࡀ㜼ᐖࡉࢀ࡚ࡋࡲࡗࡓࡶࡢ࡜⪃࠼ࡽࢀࡓࠋ୍᪉ࠊࣛࢡ ࢺ࣮ࢫ6 ఩Ỉ㓟ᇶࡣㄆ㆑࡟ࡣ㔜せ࡛ࡣ࡞࠸఩⨨࡛࠶ࡗࡓࡓࡵࠊࡇࡕࡽࢆ⨨᥮ࡋࡓ 6-࣓ࢳࣝ ࢭࣞࣀࣛࢡࢺ࣮ࢫࡣ࢞ࣞࢡࢳࣥ-9 ࡟ࡼࡿㄆ㆑ࡀྍ⬟࡛࠶ࡗࡓ࡜⤖ㄽ௜ࡅࡓࠋ

(27)

➨ ➨㸳❶ ࢭࣞࣥᶆ㆑⢾㙐࡬ࡢMAD ἲࡢ㐺⏝࡜ඹ⤖ᬗ X ⥺ᵓ㐀ゎᯒ ➨4 ❶࡛ࠊ6 ࣓ࢳࣝࢭࣞࣀࣛࢡࢺ࣮ࢫࡀࣄࢺ࢞ࣞࢡࢳࣥ-9 NCRD ࡟ㄆ㆑ࡉࢀࡿࡇ࡜ࡀศ࠿ ࡗࡓࠋ⥆࠸࡚ඹ⤖ᬗ໬ࠊX ⥺⤖ᬗᵓ㐀ゎᯒࢆ⾜࠺ࡇ࡜࡜ࡋࡓࠋඹ⤖ᬗ໬࡟⏝࠸ࡿࣂࢵࣇ࢓࣮ ࢆ✀ࠎ᳨ウࡋࡓ⤖ᯝࠊࢢࣝࢥ࣮ࢫ6 ఩࡟࣓ࢳࣝࢭࣞࣀᇶࢆ᭷ࡍࡿࣛࢡࢺ࣮ࢫㄏᑟయ 2 ࡛ࡣࠊ ඹ⤖ᬗࡢసᡂ࡟ᡂຌࡋࡓ (Figure 6)ࠋࡋ࠿ࡋ࡞ࡀࡽࠊ࢞ࣛࢡࢺ࣮ࢫ 6 ఩࡟࣓ࢳࣝࢭࣞࣀᇶࢆ ᭷ࡍࡿࣛࢡࢺ࣮ࢫㄏᑟయ1 ࡛ࡣඹ⤖ᬗࢆᚓࡿࡇ࡜ࡀ࡛ࡁ࡞࠿ࡗࡓࠋ Figure 6. 6-MeSe ࣛࢡࢺ࣮ࢫ࡜ࣄࢺ࢞ࣞࢡࢳࣥ-9 NCRD ࡢඹ⤖ᬗ. <ඹ⤖ᬗ໬᮲௳> hG9NCRD (5 mg/mL) + 6-MeSe-Lactose (10 mM) 10% PEG 6000, 100 mM Tris (pH 7.5), 16 ºC

ࣄࢺ࢞ࣞࢡࢳࣥ-9 NCRD ࡜ 6-࣓ࢳࣝࢭࣞࣀࣛࢡࢺ࣮ࢫ 2 ࡢඹ⤖ᬗ࡟㛵ࡋ࡚ࠊ㧗࢚ࢿࣝࢠ

࣮ຍ㏿ჾ◊✲ᶵᵓࡢࣅ࣮࣒ࣛ࢖ࣥBL-17A ࡛ࠊSAD ࠾ࡼࡧ MAD ࡟࡚␗ᖖศᩓࢆ ᐃࡋࡓ࡜

ࡇࢁࠊSADࠊMAD ࡢ࡝ࡕࡽ࡛ࡶ༑ศ࡞␗ᖖᩓ஘ຠᯝࢆᚓࡽࢀࡓࠋࡑࡢᚋࠊ✀ࠎࡢࣉࣟࢢࣛ ࣒࡟ࡼࡾ㟁Ꮚᐦᗘᅗࡢィ⟬ࢆ⾜ࡗࡓ (Figure 7)ࠋ

Figure 7. ࢭࣞࣀࣛࢡࢺ࣮ࢫ㏆ഐࡢ㟁Ꮚᐦᗘᅗ

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- 26 - Figure 8. A) ࣄࢺ࢞ࣞࢡࢳࣥ-9 NCRD ࡜ α-ࣛࢡࢺ࣮ࢫࡢࣜ࣎ࣥࣔࢹࣝ (PDB id: 2EAK),

B) ࣄࢺ࢞ࣞࢡࢳࣥ-9 NCRD ࡜ 6-MeSe-ࣛࢡࢺ࣮ࢫࡢࣜ࣎ࣥࣔࢹࣝ(PDB id: 3WLU)

㐣ཤ࡟ሗ࿌ࡉࢀࡓࣄࢺ࢞ࣞࢡࢳࣥ-9 NCRD ࡜D-ࣛࢡࢺ࣮ࢫࡢඹ⤖ᬗࡢ❧యᵓ㐀ゎᯒࡢ⤖

ᯝ10 (A)࡜௒ᅇᚓࡽࢀࡓࣄࢺ࢞ࣞࢡࢳࣥ-9 NCRD ࡜ 6-࣓ࢳࣝࢭࣞࣀࣛࢡࢺ࣮ࢫࡢඹ⤖ᬗࡢ❧

యᵓ㐀ゎᯒࡢ⤖ᯝ (B)ࢆẚ㍑ࡍࡿ࡜ࠊྠࡌ⢾㙐ㄆ㆑ࢧ࢖ࢺ࡛ྠᵝ࡟⢾㙐ࡀㄆ㆑ࡉࢀ࡚࠸ࡿࡇ

࡜ࡀ☜ㄆࡉࢀࡓࠋࡲࡓࠊ⢾ࡢỈ㓟ᇶ࡜⺮ⓑ㉁୰ࡢ࢔࣑ࣀ㓟ṧᇶ࡜ࡢỈ⣲⤖ྜࡢ┦㛵࡟ࡘ࠸ ࡚ࡶࠊࡼࡃ୍⮴ࡋࡓ (Figure 9)ࠋ

(29)

Figure 9. a), b) ࣄࢺ࢞ࣞࢡࢳࣥ-9 NCRD ⢾㙐ㄆ㆑㒊఩࿘㎶ࡢᶍᘧᅗ. ⢾㙐࡜┦㛵ࡢ࠶ࡿ࢔࣑ ࣀ㓟ṧᇶࡣᲬࣔࢹ࡛ࣝ⾲ࡋࡓ. a) α-ࣛࢡࢺ࣮ࢫ࡜⤖ྜࡋࡓሙྜ. b) 6-MeSe-ࣛࢡࢺ࣮ࢫ࡜⤖ྜ ࡋࡓሙྜ. c), d) Ỉ⣲⤖ྜࡢᶍᘧᅗ. Ỉ⣲⤖ྜࡣ◚⥺࡛⾲ࡋࠊῧ࠼ᏐࡢᩘᏐࡣ⤖ྜ㊥㞳 (Å) ࢆ⾲ࡋࡓ. c) α-ࣛࢡࢺ࣮ࢫ࡜ࣄࢺ࢞ࣞࢡࢳࣥ-9 NCRD ࡜ࡢỈ⣲⤖ྜࡢᵝᏊ. d) 6-MeSe-ࣛࢡࢺ ࣮ࢫ࡜ࣄࢺ࢞ࣞࢡࢳࣥ-9 NCRD ࡜ࡢỈ⣲⤖ྜࡢᵝᏊ. ௨ୖࡢẚ㍑࠿ࡽࠊ6-࣓ࢳࣝࢭࣞࣀࣛࢡࢺ࣮ࢫࡣࣄࢺ࢞ࣞࢡࢳࣥ-9 NCRD ࡢ⢾㙐ㄆ㆑ࢧ࢖ࢺ ࡟ࠊᮍᶆ㆑ࡢD-ࣛࢡࢺ࣮ࢫ࡜ྠᵝ࡟ㄆ㆑ࡉࢀࡿࡇ࡜ࡀ☜ㄆࡉࢀࠊࡲࡓࠊ⢾㙐୰ࡢࢭࣞࣥཎᏊ ࡢ␗ᖖศᩓຠᯝࢆ฼⏝ࡋ࡚❧యᵓ㐀Ỵᐃࡢ㝿ࡢ఩┦Ỵᐃࡀྍ⬟࡛࠶ࡗࡓࠋࡇࡢࡇ࡜࠿ࡽࠊ ࢭࣞࣥᶆ㆑⢾㙐ࡣ⢾㙐-⺮ⓑ㉁」ྜయࡢ❧యᵓ㐀ゎᯒࡢ᭷ຊ࡞⢾㙐ࢶ࣮ࣝ࡜ࡋ࡚ാࡃࡇ࡜ࡀ ☜ㄆࡉࢀࡓࠋ

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- 28 - ⥲ ⥲ᣓ ➨ 2 ❶࡟࠾࠸࡚ࠊ⬺㞳ᇶ࡟ࣇࢵ⣲ཬࡧࢺࣜࢡࣟࣟ࢔ࢭࢺ࢖࣑ࢹ࣮ࢺᇶࢆᣢࡘࢭࣞࣀ໬⢾ ౪୚య࡜ࠊ㟁Ꮚ౪୚ᛶࡢ࢚࣮ࢸࣝ⣔ಖㆤᇶࢆ᭷ࡍࡿ⢾ཷᐜయ࡜ࡢ཯ᛂࢆ⾜࠺ࡇ࡜࡛ࢭࣞࣥ ࢆ᭷ࡍࡿ஧⢾ࡢྜᡂ࡟ᡂຌࡋࡓࠋࡲࡓࠊ➨ 3 ❶࡟࠾࠸࡚ࡣࠊࢭࣞࣥཎᏊࢆ᭷ࡍࡿཷᐜయࢆ ⏝࠸࡚ࡢ஧⢾ྜᡂ࡟ࡶᡂຌࡋࡓࠋ௒ᅇࠊࢭࣞࣥࢆ᭷ࡍࡿ⢾౪୚యࠊ⢾ཷᐜయࢆ㛤Ⓨࡋࢢࣜ ࢥࢩࣝ໬࡟ᡂຌࡋࡓࡇ࡜ࡣࠊ௒ᚋࡢࢭࣞࣀ⢾㙐ࡢྜᡂ࡟ྥࡅࡓ኱ࡁ࡞ᡂᯝ࡛࠶ࡿ࡜⪃࠼ࡽ ࢀࡿࠋ ࡲࡓࠊ➨4 ❶࡟࠾࠸࡚ࡣࠊSPR ヨ㦂࡟ࡼࡾࠊ6 ఩ࢭࣞࣀయࡣ࢞ࣞࢡࢳࣥ-9 ࡟⤖ྜᛶࢆ♧ࡍ ࡇ࡜ࡀࢃ࠿ࡾࠊ6’఩ࢭࣞࣀయࡣ࢞ࣞࢡࢳࣥ-9 ࡟ᑐࡋ࡚⤖ྜᛶࢆ♧ࡉ࡞࠸ࡇ࡜ࡀࢃ࠿ࡗࡓࠋࡇ ࡢࡇ࡜ࡣࠊ➨5 ❶࡟࠾࠸࡚ࠊ6 ఩ࢭࣞࣀయࡣ࢞ࣞࢡࢳࣥ-9 ࡜ࡢඹ⤖ᬗࢆᙧᡂࡋࠊ6’఩ࢭࣞࣀ య2 ࡣ࢞ࣞࢡࢳࣥ-9 ࡜ࡢඹ⤖ᬗࢆᙧᡂ࡛ࡁ࡞࠿ࡗࡓࡇ࡜࡜┦㛵ࡋ࡚࠾ࡾࠊ➨ 1 ❶࡟࠾࠸࡚ ㆟ㄽࡋࡓỈ㓟ᇶࢆ࣓ࢳࣝࢭࣞࣀᇶ࡛⨨᥮ࡍࡿ㝿࡟ࡣ᭱㐺࡞఩⨨ࢆ㑅ᢥࡍࡿᚲせᛶࡀ࠶ࡿ࡜ ࠸࠺ࡇ࡜ࡢド᫂࡜࡞ࡗࡓࠋ ➨5 ❶࡟࠾࠸࡚ࡣࠊ6 ఩ࢭࣞࣀయ࡜ࣄࢺ࢞ࣞࢡࢳࣥ-9 NCRD ࡢඹ⤖ᬗࡘ࠸࡚ MAD ἲࢆ⏝ ࠸࡚⢾㙐୰ࡢࢭࣞࣥཎᏊࢆᶆⓗ࡜ࡋ఩┦Ỵᐃࢆ⾜࠸❧యᵓ㐀ゎᯒ࡟ᡂຌࡋࡓࠋࡲࡓࠊ௒ᅇ Ỵᐃࡋࡓ❧యᵓ㐀ࡣࠊ㐣ཤ࡟ሗ࿌ࡉࢀࡓD-ࣛࢡࢺ࣮ࢫ࡜ࣄࢺ࢞ࣞࢡࢳࣥ-9 NCRD ࡢඹ⤖ᬗ ࡢ❧యᵓ㐀ゎᯒࡢ⤖ᯝ࡜ྠᵝ࡛࠶ࡗࡓࠋࡇࡢࡇ࡜࡟ࡼࡾࠊࢭࣞࣥᶆ㆑⢾㙐ࡀX ⥺⤖ᬗᵓ㐀ゎᯒࡢ఩┦ỴᐃศᏊࢶ࣮ࣝ࡜ࡋ࡚᭷⏝࡛࠶ࡿࡇ࡜ࡀ♧ࡉࢀࡓࠋ

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➨ ➨㸰㒊

࢔ࢭࢱ࣮ࣝ஺᥮཯ᛂࢆ฼⏝ࡍࡿ᪂つࢭࣞࣥᑟධ཯ᛂࡢ㛤Ⓨ

➨㸯❶ ᪂つࢭࣞࣥᑟධ཯ᛂࡢ㛤Ⓨᡓ␎ ➨㸯㒊࡟࡚ࠊࢭࣞࣥᶆ㆑ࣛࢡࢺ࣮ࢫ࡜ࣄࢺ࢞ࣞࢡࢳࣥ-9 NCRD ࡜ࡢ MAD ἲ࡟ࡼࡿ X ⥺ ⤖ᬗᵓ㐀ゎᯒࢆ㐩ᡂࡍࡿࡇ࡜ࡀ࡛ࡁࡓࠋࡋ࠿ࡋ࡞ࡀࡽࠊ1 ࡘࡢࢭࣞࣥཎᏊ࡟ࡼࡾ఩┦Ỵᐃࡀ ྍ⬟࡞ศᏊ㔞ࡢୖ㝈ࡣ20 kDa㸦ࡲࡓࡣ 200 ࢔࣑ࣀ㓟ṧᇶ㸧ࡀୖ㝈࡜ࡉࢀ࡚࠾ࡾࠊ኱ᆺ⺮ⓑ ㉁࡬ࡢMAD ἲࡢ㐺⏝࡟ࡣࢭࣞࣥከ⨨᥮⢾㙐ࡀᚲせ࡜࡞ࡿࠋࡑࡇ࡛ࠊ➨ 2 㒊࡛ࡣࠊ᪤࡟⢾㙐 ୰࡟ᑟධࡉࢀ࡚࠸ࡿࢭࣞࣥཎᏊ࡟ᙳ㡪ࢆ୚࠼ࡿࡇ࡜࡞ࡃࠊ⡆౽࡟✜࿴࡞᮲௳࡛ࢭࣞࣥ⨨᥮ ᩘࢆቑຍࡉࡏࡿ᪉ἲࡢ㛤Ⓨࢆ⾜࠺ࡇ࡜࡜ࡋࡓࠋ ᪂ࡓ࡟ࢭࣞࣥࡢᑟධ࡟฼⏝ࡋࡼ࠺࡜⪃࠼ࡓࡢࡀࠊ⢾㙐໬Ꮫ࡟࠾࠸࡚ࡋࡤࡋࡤほᐹࡉࢀࡿ ࢔ࢭࢱ࣮ࣝ஺᥮཯ᛂࡢ୍ࡘ࡛࠶ࡿࠊ࢔ࢢࣜࢥࣥ㌿⛣཯ᛂ24࡛࠶ࡿ (Scheme 17)ࠋ Scheme 17

24_{a) J. Kihlberg, E. Eichler, D. R. Bundle, Carbohydr. Res. 1991, 211, 59-75. b) S. Knapp, S. R.}

Nandan, J. Org. Chem. 1994, 58, 281−283. c) D. A. Leigh, J. P. Smart, A. M. Truscello. Carbohydr.

Res. 1995, 276, 417-424. d) F. Belot, J. C. Jacquinet, Carbohydr. Res. 1996, 290, 79-86. e) Y. G. Du,

J. H. Lin, R. J. Linhardt, J. Carbohydr. Chem. 1997, 16, 1327-1344. f) H. Yu, B. Yu, X. Y. Wu, Y. Z. Hui, X. W. Han, J. Chem. Soc. Perkin Trans. 12000, 1445-1453. g) T. Zhu, G.-J Boons, Carbohydr.

Res. 2000, 329, 709-715. h) A. A. Sherman, O. N. Yudina, Y. V. Mironov, E. V. Sukhova, A. S.

Shashkov, V. M. Menshov, N. E. Nifantiev, Carbohydr. Res. 2001, 336, 13-46. i) P. E. Cheshev, L. O. Kononov, Y. E. Tsvetkov, A. S. Shashkov, N. E. Nifantiev, Russ. J. Bioorg. Chem. 2002, 28, 419−429. j) R. Geurtsen, G.-J. Boons, Tetrahedron Lett. 2002, 43, 9429−9431. k) H. Tanaka, M. Adachi, T. Takahashi, Tetrahedron Lett. 2004, 45, 1433-1436. l) J. Xue, S. D. Khaja, R. D. Locke, K. L. Matta,

Synlett 2004, 861-865. m) J. D. C. Codee, B. Stubba, M. Schiattarella, H. S. Overkleeft, C. A. A. van

Boeckel, J. H. van Boom, G. A. van der Marel, J. Am. Chem. Soc. 2005, 127, 3767−3773. n) J. S. Sun, X. W. Han, B. Yu, Org. Lett. 2005, 7, 1935-1938. o) Z. Li, J. C. Gildersleeve, Tetrahedron Lett. 2007, 48, 559−562. p) M. Kato, G. Hirai, M. Sodeoka, Chem. Lett. 2011, 40, 877-879. q) F. Yu, H. M. Nguyen, J. Org. Chem. 2012, 77, 17, 7330-7343.

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- 30 - ࢢࣜࢥࢩࣝ໬཯ᛂ࡟࠾࠸࡚⢾౪୚యࢆάᛶ໬ࡋࡓ㝿࡟Ⓨ⏕ࡍࡿ࢜࢟ࢯ࢝ࣝ࣋ࢽ࣒࢘࢖࢜ ࣥ୰㛫య࡟ᑐࡋ࡚ࠊ⢾ཷᐜయࡢỈ㓟ᇶࡢ㓟⣲ཎᏊࡼࡾࡶࠊ⢾ཷᐜయ࢔ࢢࣜࢥࣥ㒊఩ࡢ㟁Ꮚ ㇏ᐩ࡞◲㯤ཎᏊࡀඃඛࡋ࡚ࠊồ᰾ᨷᧁࢆ⾜࠸ࠊ⎔ෆ㓟⣲࠿ࡽࡢ㟁Ꮚࡢᢲࡋฟࡋࢆ⤒࡚ࠊ࢔ ࣝ࢟ࣝࢳ࢜ᇶࡀ㌿⛣ࡍࡿ࡜࠸࠺ࡶࡢ࡛࠶ࡿࠋࢭࣞࣥཎᏊࡣ◲㯤ࡼࡾࡶ㧗࠸HOMO (nse)ࢆ᭷ ࡍࡿࡓࡵࠊࡇࡢࡼ࠺࡞࢔ࢭࢱ࣮ࣝ஺᥮཯ᛂ࡟࠾࠸࡚ࡶࠊຠ⋡ࡼࡃ཯ᛂࡀ㐍⾜ࡍࡿ࡜ண᝿࡛ ࡁࡿࠋࡇࡢ⌧㇟࡟Ⓨ᝿ࢆᚓ࡚ࠊᮏ◊✲࡛ࡣࠊ᪂ࡓ࡞ࢭࣞࣀ໬཯ᛂ⏝ヨ⸆ࡢ㛤Ⓨࢆ⾜࠺ࡇ࡜ ࡜ࡋࡓࠋヨ⸆ࡢタィ࡟࠶ࡓࡾࠊ⢾⎔ᵓ㐀୰ࡢ㓟⣲ཎᏊ࡜◲㯤ཎᏊࡢ࣊ࢸࣟ࢔ࢭࢱ࣮ࣝᵓ㐀 ࡟╔┠ࡋࠊࡇࡢᵓ㐀ࢆᶍೌࡋ⡆␎໬ࡋࡓ┤㙐ᆺࢭࣞࣀ࢔ࢭࢱ࣮࡛ࣝ࠶ࡿBOMSeR (R = Me, Ph, SE)ࢆタィࡋࡓ (Scheme 18)ࠋ Scheme 18 㓟⣲ཎᏊഃࡢ⨨᥮ᇶ࡟ࡣࠊ཯ᛂ᫬ࡢTLC ㏣㊧ࢆᐜ᫆࡟ࡍࡿࡓࡵࠊUV ྾཰ࡀ࠶ࡿ BOM ᇶ ࢆ㑅ᢥࡋࡓࠋ୍᪉ࠊࢭࣞࣥཎᏊഃࡢ⨨᥮ᇶ࡟ࡣ❧య㞀ᐖࡀ᭱ᑠࡢMe ᇶࠊࢢࣜࢥࢩࣝ໬࡟࠾ ࡅࡿ⢾౪୚యࡢ࢔ࢢࣜࢥࣥࡢ⬺㞳ᇶ࡜ࡋ࡚ࡢ᭷⏝ᛶࡀ᳨ドࡉࢀ࡚࠸ࡿPh ᇶ25ࠊࡲࡓࠊ࢔ࢢ ࣜࢥࣥ࡬ࡢࢭࣞࣥᑟධᚋ࡟௚ࡢ⨨᥮ᇶ࡬ኚ᥮ࡀྍ⬟࡞SE ᇶ13_{ࢆᑟධࡍࡿࡇ࡜࡜ࡋࡓࠋ}

25_{a) A. Mallet, J. M. Mallet, P. Sinay, Tetrahedron Asym. 1994, 5, 12, 2593-2608, b) P. Grice, S. V.}

Ley, J. Pietruszka, H. W. M. Priepke, E. P. E. Walther, Synlett 1995, 7, 781-784, c) T. Furuta, K. Takeuchi, M. Iwamura, Chem. Commun. 1996, 2, 157-158. d) R. V. Stick, D. M. G. Tilbrook, S. J. Williams, Aust. J. Chem. 1997, 50, 3, 237-240. e) P. Grice, S. V. Ley, J. Pietruszka, H. M. I. Osborn, H. W. M. Priepke, S. L. Warriner, Chem. Eur. J. 1997, 3, 3, 431-440. e) N. L. Douglas, S. V. Ley, U. Lücking, S. L. Warriner, J. Chem. Soc., Perkin Trans. 1 1998, 51-66, f) S. Mehta, B. M. Pinto,

Carbohydr. Res. 1998, 310, 1-2, 43-51. g) P. Langer, S. J. Ince, S. V. Ley, Steven V. J. Chem. Soc., Perkin Trans. 1 1998, 23, 3913-3916. h) D. K. Baeschlin, L. G. Green, M. G. Hahn, B. Hinzen, S. J.

Ince, S. V. Ley, Tetrahedron Asym. 2000, 11, 1, 173-197. i) S. Yamago, T. Yamada, O. Hara, H. Ito, Y. Mino, J.-I. Yoshida, Org. Lett. 2001, 3, 24, 3867-3870. j) S. C. Ennis, I. Cumpstey, A. J. Fairbanks, T. D. Butters, M. Mackeen, M. R. Wormald, Tetrahedron 2002, 58. 46, 9403-9411. k) S. Yamago, K. Kokubo, O. Hara, S. Masuda, J.-I. Yoshida, J. Org. Chem. 2002, 67, 24, 8584-8592. l) R. N. MacCoss, P. E. Brennan, S. V. Ley, Org. Biomol. Chem. 2003, 1, 12, 2029-2031. m) R. R. France, R. G. Compton, B. G. Davis, A. J. Fairbanks, N. V. Rees, J. D. Wadhawan, Org. Biomol. Chem. 2004, 2, 15, 2195-2202. n) S. Yamago, T. Yamada, H. Ito, O. Hara, Y. Mino, J.-I. Yoshida, Chem. Eur. J. 2005,

11, 21, 6159-6174. o) R. M. van Well, T. S. Kärkkäinen, K. P. R. Kartha, R. A. Field, Carbohyd. Res.

2006, 341, 10, 1391-1397. p) S. Valerio, A. Iadonisi, M. Adinolfi, A. Ravida, J. Org. Chem. 2007, 72, 16, 6097-6106. q) I. Cumpstey, D. Crich, J. Org. Chem. 2011, 30, 7-9, 469-485. r) M. Spell, X. Wang, A. E. Wahba, E. Conner, J. Ragains, Carbohydr. Res. 2013, 369, 42-47.

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➨ ➨㸰❶ ┤㙐ᆺࢭࣞࣀ࢔ࢭࢱ࣮ࣝヨ⸆ࡢ㛤Ⓨ ࡲࡎࠊBOMSeMe㸦໬ྜ≀ 51㸧ࡢྜᡂࢆ⾜ࡗࡓࠋࢪ࣓ࢳࣝࢪࢭࣞࢽࢻ࡟Ỉ⣲໬࣍࢘⣲ࢼࢺ ࣒ࣜ࢘ࢆస⏝ࡉࡏࠊⓎ⏕ࡋࡓ࣓ࢳࣝࢭࣞࣀ࢔ࢽ࢜ࣥ࡬ồ㟁Ꮚ๣࡜ࡋ࡚BOMCl ࢆ཯ᛂࡉࡏࡿ ࡇ࡜࡛⡆౽࡟ㄪ〇ࡋࡓࠋBOMSePh㸦໬ྜ≀ 52㸧࡟ࡘ࠸࡚ࡣ BOMSeMe㸦໬ྜ≀ 51㸧࡜ྠᵝ ࡟ࢪࣇ࢙ࢽࣝࢪࢭࣞࢽࢻࢆཎᩱ࡜ࡍࡿࡇ࡜࡛ࡇࡕࡽࡶ⡆౽࡟ㄪ〇ࡋࡓࠋBOMSeSE㸦໬ྜ≀ 53 ࡟ࡘ࠸࡚ࡣࠊTolSeSE26ࢆཎᩱ࡜ࡋࠊTol ᇶࢆ࢔࣑ࣥ࡟ࡼࡾάᛶ໬ࡋ BOMCl ࢆస⏝ࡉࡏࡿ ࡇ࡜࡛ㄪ〇ࡋࡓ (Scheme 19)ࠋ

Scheme 19

⥆࠸࡚ࠊྛ✀࢖࣑ࢹ࣮ࢺ౪୚య࡬ࡢࢭࣞࣥࡢᑟධ᳨ウࢆ⾜ࡗࡓࠋጞࡵ࡟BOMSeMe㸦໬ྜ

≀51㸧ࢆ⏝࠸ࡓࢭࣞࣥཎᏊᑟධࡢ᳨ウࢆ⾜ࡗࡓ (Table 3)ࠋ

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- 32 - Table 3 Entry 1 ࡛ࡣ࢞ࣛࢡࢺ࣮ࢫࡢࢺࣜࢡࣟࣟ࢔ࢭࢺ࢖࣑ࢹ࣮ࢺయࢆ⏝࠸ࡓࠋࢪࢡ࣓ࣟࣟࢱࣥ⁐ ፹୰ࠊTMSOTf Ꮡᅾୗ࢖࣑ࢹ࣮ࢺ 44 ࡜཯ᛂࡉࡏࡿࡇ࡜࡛ࠊBOMSeMe㸦໬ྜ≀ 51㸧ࡣ཰⋡ 81%࡛E-ࢭࣞࣀࢢࣜࢥࢩࢻࡢࡳࢆ୚࠼ࡓࠋ⥆࠸࡚஧⢾࡬ࡢᑟධࡢ᳨ウ࡜ࡋ࡚ࠊEntry 2 ࡛ࡣࣛ ࢡࢺ࣮ࢫࡢࢺࣜࢡࣟࣟ࢔ࢭࢺ࢖࣑ࢹ࣮ࢺయ 5427ࢆ⏝࠸ࡓࠋEntry 2 ࡛ࡶEయࡢࡳ཰⋡ 70%࡛ ᚓࡿࡇ࡜࡟ᡂຌࡋࡓࠋ⥆࠸࡚ࢩ࢔ࣜࣝ࢞ࣛࢡࢺ࣮ࢫࡢࢺࣜࢡࣟࣟ࢔ࢭࢺ࢖࣑ࢹ࣮ࢺయ28㸦໬ ྜ≀55㸧࡟ࡘ࠸࡚ࡶᑟධ᳨ウࢆ⾜ࡗࡓࠋEntry 3 ࡛ࡣࢪࢡ࣓ࣟࣟࢱࣥ⁐፹୰཯ᛂࢆ⾜ࡗࡓࡀࠊ ୺⏕ᡂ≀࡛࠶ࡿEయ࡜ᚤ㔞⏕ᡂࡋࡓDయ࡜⪃࠼ࡽࢀࡿ⏕ᡂ≀࡜ࡢ༢㞳ࡀᅔ㞴࡜࡞ࡗࡓࠋࡑࡇ ࡛ࠊEntry 4 ࡛ࡣࠊDయࡢ⏕ᡂࢆᢚไࡍࡿࡇ࡜ࢆ≺࠸ࠊࢽࢺࣜࣝ⁐፹ຠᯝࢆ⏝࠸ࡿࡇ࡜࡜ࡋࠊ ࢪࢡ࣓ࣟࣟࢱࣥ-ࣉࣟࣆ࢜ࢽࢺࣜࣝࡢΰྜ⁐ᾮ୰࡛཯ᛂࢆ⾜ࡗࡓ࡜ࡇࢁࠊDయࡢ⏕ᡂ࡞ࡃࠊ཰ ⋡83%࡛Eయࡢࡳࢆᚓࡿࡇ࡜࡟ᡂຌࡋࡓࠋ

27_{G. J. P. H. Boons, F. L. van Delft, P. A. M. van der Klein, G. A. van der Marel, J. H. van Boom,}

Tetrahedron 1992, 48, 885-904.

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Table 4

⥆࠸࡚PhSe ᇶࡢᑟධࢆ⾜ࡗࡓ (Table 4)ࠋEntry 1 ࡛ࡣࠊ࢞ࣛࢡࢺ࣮ࢫࡢ࢖࣑ࢹ࣮ࢺయ࡜

ࡢ཯ᛂࢆ⾜ࡗࡓࡀࠊBOMSePh㸦໬ྜ≀ 52㸧1.0 ➼㔞ࢆ⏝࠸ࡓሙྜࠊ཯ᛂ୰࡟ BOMSePh ࡀศ ゎࡋ⏕ᡂࡋࡓ࣋ࣥࢪࣝ࢜࢟ࢩ࣓ࢳࣝ࢔ࣝࢥ࣮ࣝࢆ⤒⏤ࡋ࡚⏕ᡂࡋࡓ࡜⪃࠼ࡽࢀࡿBOM ࢢ ࣜࢥࢩࢻࡀ๪⏕ࡋ⢭〇ࡀᅔ㞴࡜࡞ࡗࡓࠋࡑࡇ࡛ࠊEntry 2 ࡛ࡣࠊBOMSePh㸦໬ྜ≀ 52㸧ࢆ 2.0 ➼㔞ࠊTMSOTf ࢆ 0.6 ➼㔞࡟ቑࡸࡋࠊ཯ᛂࢆ⾜ࡗࡓ࡜ࡇࢁ㧗཰⋡ 99%࡟࡚໬ྜ≀ࡢEయࡢ ࡳࢆᚓࡿࡇ࡜ࡀ࡛ࡁࡓࠋEntry 3 ࡛ࡣ㐺⏝࡛ࡁࡿᇶ㉁ࡢᣑ኱ࢆᅗࡾࠊࢩ࢔ࣝ㓟౪୚య࡬ࡢᑟ ධࢆ᳨ウࡋࡓࠋࡇࡢ㝿ࡢࠊࢢࣜࢥࢩࣝ࢖࣑ࢹ࣮ࢺ࡟ࡣࢩ࢔ࣝ㓟ࢢࣜࢥࢩࢻྜᡂ᫬࡟⏝࠸ࡽ ࢀࡿN-ࣇ࢙ࢽࣝࢺࣜࣇࣝ࢜ࣟ࢔ࢭࢺ࢖࣑ࢹ࣮ࢺ29㸦໬ྜ≀59㸧ࢆ⏝࠸ࡓࠋࣉࣟࣆ࢜ࢽࢺࣜ ࣝ⁐፹୰࡛཯ᛂࢆ⾜ࡗࡓ࡜ࡇࢁ཰⋡90%ࠊD:E㸻2:1 ࡛໬ྜ≀ࢆᚓࡿࡇ࡜࡟ᡂຌࡋࡓࠋ

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- 34 - Tabele 5

᭱ᚋ࡟ࠊBOMSeSE㸦໬ྜ≀ 53㸧ࢆ⏝࠸ࡓ᳨ウࢆ⾜ࡗࡓ (Table 5)ࠋEntry 1 ࡛ࡣ࢞ࣛࢡࢺ

࣮ࢫࢺࣜࢡࣟࣟ࢔ࢭࢺ࢖࣑ࢹ࣮ࢺ44 ࡟ᑐࡋ࡚ࡢ SESe ᇶࡢᑟධࢆ⾜ࡗࡓ࡜ࡇࢁࠊ཰⋡ 90% ࡛Eయࡢࡳࢆྜᡂࡍࡿࡇ࡜ࡀ࡛ࡁࡓࠋEntry 2 ࡛ࡣ⢾㙐ෆ㒊࡟ࢭࣞࣀࢢࣜࢥࢩࢻ⤖ྜࢆᣢࡘࢩ ࢔ࣜࣝD(2-6)࢞ࣛࢡࢺ࣮ࢫࡢࢺࣜࢡࣟࣟ࢔ࢭࢺ࢖࣑ࢹ࣮ࢺయ30_㸦໬ྜ≀_{63㸧࡟ᑐࡋ࡚ࡢ SESe} ᇶࡢᑟධࢆ⾜ࡗࡓࠋࢪࢡ࣓ࣟࣟࢱࣥ⁐፹୰࡛཯ᛂࢆ⾜ࡗࡓ࡜ࡇࢁࠊ5%࡯࡝Dయ࡜ᛮࢃࢀࡿ໬ ྜ≀ࡀ⏕ᡂࡋ⢭〇ࡀᅔ㞴࡜࡞ࡗࡓࠋࡇࢀࡣTable 3 ࡢ Entry 3 ࡢ᫬࡜㢮ఝࡋࡓ⤖ᯝ࡛࠶ࡗࡓࠋ ࡑࡇ࡛ࠊEntry 3 ࡛ࡣࠊDయࡢ⏕ᡂࢆᢚไࡍࡿࡇ࡜ࢆ≺࠸ࠊࢽࢺࣜࣝ⁐፹ຠᯝࢆ⏝࠸ࡿࡇ࡜࡜ ࡋࢪࢡ࣓ࣟࣟࢱࣥ-࢔ࢭࢺࢽࢺࣜࣝࡢΰྜ⁐ᾮ୰࡛཯ᛂࢆ⾜ࡗࡓ࡜ࡇࢁࠊ๪⏕ᡂ≀ࡢ⏕ᡂࢆ ᢚไࡍࡿࡇ࡜ࡀ࡛ࡁࠊEࢢࣜࢥࢩࢻࡢࡳࢆ 84%࡛ᚓࡿࡇ࡜࡟ᡂຌࡋࡓࠋࡲࡓࠊEntry 2,3 ࡢ⤖ ᯝࡼࡾࠊᮏ཯ᛂ᮲௳ࡣࠊෆ㒊ࡢࢭࣞࣀࢢࣜࢥࢩࢻ࡟ᙳ㡪ࢆ୚࠼ࡿࡇ࡜࡞ࡃ㑏ඖᮎ➃࡟ࢭࣞ ࣥཎᏊࢆᑟධ࡛ࡁࡿࡇ࡜ࡀ᫂ࡽ࠿࡜࡞ࡗࡓࠋEntry 4 ࡛ࡣࡼࡾ኱ࡁ࡞⢾㙐࡬ࡢᇶ㉁ᣑ኱࡜ࡋ 30_{໬ྜ≀ 63 ࡢㄪ〇࡟ࡘ࠸࡚ࡣᐇ㦂㡯࡟グ㍕ࡍࡿࠋ}

(37)

࡚ࠊ࢞ࣥࢢࣜ࢜ࢩࢻGM1 ࡢ㠀㑏ඖᮎ➃ᅄ⢾ࡢࢺࣜࢡࣟࣟ࢔ࢭࢺ࢖࣑ࢹ࣮ࢺయ31㸦໬ྜ≀64㸧 ࡟ᑐࡋ࡚ࢽࢺࣜࣝ⁐፹ຠᯝࢆ⏝࠸ࡓ᮲௳࡛཯ᛂࢆ⾜ࡗࡓ࡜ࡇࢁࠊEయࡢࡳࢆ཰⋡ 85%࡛ᚓࡿ ࡇ࡜࡟ᡂຌࡋࡓࠋ ௨ୖࡢࡼ࠺࡟ࠊࣝ࢖ࢫ㓟Ꮡᅾୗ࢖࣑ࢹ࣮ࢺ౪୚య࡟ᑐࡋࠊ3 ✀㢮ࡢࢭࣞࣀ࢔ࢭࢱ࣮ࣝࡣồ ᰾๣࡜ࡋ࡚ാࡁࠊ࢔ࣝ࢟ࣝࢭࣞࣀᇶࢆᑟධ࡛ࡁࡿࡇ࡜ࡀド࡛᫂ࡁࡓࠋ

(38)

- 36 - ➨ ➨㸱❶ ࢭࣞࣥከ⨨᥮⢾㙐ࡢྜᡂ ➨㸯⠇ ࢭࣞࣥከ⨨᥮⢾㙐ࡢྜᡂᡓ␎ ྜᡂࡋࡓ SESe ᇶࢆ᭷ࡍࡿ໬ྜ≀ 65 ࢆ⏝࠸࡚ࢭࣞࣥཎᏊࢆ୍ศᏊෆ࡟」ᩘಶ᭷ࡍࡿࢭࣞ ࣥከ⨨᥮⢾㙐ࡢྜᡂࢆ⾜࠺ࡇ࡜࡜ࡋࡓࠋᙜ◊✲ᐊ࡛ࡣࡇࢀࡲ࡛ࠊ࢔ࢢࣜࢥࣥ㒊఩ࡢSE ᇶࢆ ࣇࢵ⣲࢔ࢽ࢜ࣥ࡟ࡼࡾάᛶ໬ࡉࡏࠊⓎ⏕ࡋࡓࢭࣞࣀ࢔ࢽ࢜ࣥ࡟ᑐࡋ௵ពࡢồ㟁Ꮚ๣ࢆ཯ᛂ ࡉࡏࡿࡇ࡜࡛᪂ࡓ࡞ࢭࣞࣀࢢࣜࢥࢩࢻࢆᵓ⠏ࡍࡿ᪉ἲࢆ◊✲ࡋ࡚ࡁ࡚࠸ࡿ (Scheme 20)13ࠋ ᮏ◊✲࡛ࡶࡑࡢᡭἲࢆ᥇⏝ࡋࠊSESe ᇶࡢᙧ࡛ᑟධࡋࡓ SE ᇶࢆኚ᥮ࡋࠊ᪂ࡓ࡟ࢭࣞࣥཎᏊ ࢆ᭷ࡍࡿ࢔ࢢࣜࢥࣥࢆᑟධࡍࡿࡇ࡜࡜ࡋࡓࠋ Scheme 20 ഃ㙐ࢆタィࡍࡿ㝿࡟㔜せ࡜࡞ࡿࡢࡀࠊ࢔ࢢࣜࢥࣥࡢ࡝ࡢሙᡤ࡟ࢭࣞࣥཎᏊࢆ㓄⨨ࡍࡿ࠿ ࡛࠶ࡿࠋࡇࢀ࡟ࡼࡾࠊཷᐜయ⺮ⓑ㉁࡟ṇࡋࡃㄆ㆑ࡉࢀࡿ࠿࡝࠺࠿ࡢᡂྰ࡜ࠊඹ⤖ᬗࢆసᡂ ࡋࡓ㝿ࡢᵓ㐀Ỵᐃࡢ㞴᫆ᗘࡀኚࢃࡿࠋ⢾㙐㑏ඖᮎ➃ࡢࢢࣜࢥࢩࢻ⤖ྜࡋࡓࢭࣞࣥ㏆ഐ࡟᪂ ࡋ࠸ࢭࣞࣥࢆ㓄⨨ࡋࡓሙྜࠊ⢾㙐࡜⺮ⓑ㉁࡜ࡢㄆ㆑ࢆ㜼ᐖࡋࠊṇࡋࡃㄆ㆑ࡉࢀࡎඹ⤖ᬗࡀ సᡂ࡛ࡁ࡞࠸ྍ⬟ᛶࡀ⪃࠼ࡽࢀࡿࠋࡋ࠿ࡋ࡞ࡀࡽࠊඹ⤖ᬗࡀసᡂ࡛ࡁࡓሙྜ࡟ࡣࠊ⢾㙐㑏 ඖᮎ➃࠿ࡽࢭࣞࣥཎᏊࡲ࡛ࡢཎᏊ㛫㊥㞳ࡀ▷࠸ࡓࡵࠊඹ⤖ᬗ୰࡛ࢭࣞࣥࡢྲྀࡾ࠺ࡿ✵㛫ᗙ ᶆࡢ⮬⏤ᗘࡀᑠࡉࡃ࡞ࡾᵓ㐀Ỵᐃࢆ⾜࠸ࡸࡍ࠸⤖ᬗࡀᚓࡽࢀࡿ࡜⪃࠼ࡽࢀࡿࠋ୍᪉࡛ࠊ⢾ 㙐㑏ඖᮎ➃ࡢࢭࣞࣥ࠿ࡽ㞳ࢀࡓ఩⨨ 㸦࢔ࢢࣜࢥࣥࡢ୰࡛⢾㙐࡟⤖ྜࡋ࡚࠸࡞࠸ᮎ➃ഃ㸧࡟ ᪂ࡋ࠸ࢭࣞࣥࢆ㓄⨨ࡋࡓሙྜࠊ⢾㙐࡜⺮ⓑ㉁࡜ࡢㄆ㆑ࢆ㜼ᐖࡍࡿྍ⬟ᛶࡣప࠸࡜⪃࠼ࡽࢀ ࡿࠋࡋ࠿ࡋ࡞ࡀࡽࠊඹ⤖ᬗࢆసᡂࡋࡓሙྜ࡟ࡣࠊ⢾㙐㑏ඖᮎ➃࠿ࡽࢭࣞࣥཎᏊࡲ࡛ࡢཎᏊ 㛫㊥㞳ࡀ㛗ࡃ࡞ࡿࡓࡵࠊࢭࣞࣥࡢྲྀࡾ࠺ࡿ✵㛫ᗙᶆࡢ⮬⏤ᗘࡀ኱ࡁࡃ࡞ࡾࠊ✵㛫ᗙᶆࡀ୍ ᐃ࡟ᐃࡲࡽࡎᵓ㐀Ỵᐃࡀᅔ㞴໬ࡍࡿྍ⬟ᛶࡀ⪃࠼ࡽࢀࡿࠋ ࡇࢀࡽࡢᠱ᱌஦㡯ࢆ㋃ࡲ࠼ࠊ3 ✀㢮ࡢࢭࣞࣥࢆ᭷ࡍࡿồ㟁Ꮚ๣ࢆタィࡋࠊከ⨨᥮ࢭࣞࣀ⢾

(39)

㙐ࢆᵓ⠏ࡋඹ⤖ᬗ໬࡬㐺⏝ࡋ᳨ドࡍࡿࡇ࡜࡜ࡋࡓ (Scheme 21)ࠋ Scheme 21 ᮏ◊✲࡛タィࡋࡓồ㟁Ꮚ๣ࡣࠊࢭࣞࣥཎᏊྠኈࢆ┤᥋⤖ྜࡉࡏࡓࢪࢭࣞࢽࢻᆺࠊ2 Ⅳ⣲ࢆ ௓ࡋࡓඛ࡟ࢭࣞࣥࢆᑟධࡋࡓC2 ᆺࠊ3 Ⅳ⣲ࢆ௓ࡋࡓඛ࡟ࢭࣞࣥࢆᑟධࡋࡓ C3 ᆺࡢ 3 ࡘ࡛ ࠶ࡿࠋྛồ㟁Ꮚ๣࡟ᑟධࡍࡿࢭࣞࣥཎᏊ࡟ࡘ࠸࡚ࡣࠊ❧య㞀ᐖࡀ᭱ᑠࡢಖㆤᇶ࡜ࡋ࡚ാࡃ Me ᇶ࡛ಖㆤࡍࡿࡇ࡜࡜ࡋࡓࠋC1 ᆺࡢタィࡶ⪃࠼ࡽࢀࡓࡀࠊ࢔ࢢࣜࢥࣥ࡟ᑟධᚋࠊᵓ⠏ࡉ ࢀࡿᵓ㐀ࡀ┤㙐≧ࡢࢪࢭࣞࣀ࢔ࢭࢱ࣮ࣝᵓ㐀࡛࠶ࡾࠊࡇࡢᵓ㐀ࡣྜᡂ౛ࡀᑡ࡞ࡃ≀ᛶࡀண ࡛ࡁ࡞࠿ࡗࡓࡓࡵ௒ᅇࡣྜᡂࡢᑐ㇟࠿ࡽ㝖እࡋࡓࠋ

(40)

- 38 - ➨ ➨㸰⠇ ࣓ࢳࣝࢭࣞࣀᇶࢆ᭷ࡍࡿồ᰾๣ࡢ㛤Ⓨ ጞࡵ࡟ࢪࢭࣞࢽࢻᆺࡢྜᡂ࡟࡜ࡾ࠿࠿ࡗࡓࠋࢪࢭࣞࢽࢻᆺࢆసࡿࡓࡵ࡟ࡣࠊ࣓ࢳࣝࢭࣞ ࣀ࢝ࢳ࢜ࣥࢆᨺฟ࡛ࡁࡿヨ⸆ࡢ㛤Ⓨࡀᚲせ࡜࡞ࡿࠋࡑࡇ࡛ࠊ⬺㞳ᛶࡢ㧗࠸ࢺࢩࣝᇶࢆ᭷ࡍ ࡿヨ⸆࡜ࡋ࡚MeSeTs㸦໬ྜ≀ 68㸧ࡢྜᡂࢆ⾜ࡗࡓࠋ㉸ཎᏊ౯ࣚ࢘⣲ヨ⸆࡛࠶ࡿࣅࢫࢺࣜࣜ ࣇࣝ࢜ࣟ࢔ࢭࢺ࢟ࢩ࣮ࣚࢻ࣋ࣥࢮࣥࢆ⏝࠸ࡓ⣔32࡛ࠊࢪ࣓ࢳࣝࢪࢭࣞࢽࢻ࡜ࢫࣝࣇ࢕ࣥ㓟ࢼ ࢺ࣒ࣜ࢘࡜ࡢ཯ᛂ࠿ࡽMeSeTs㸦໬ྜ≀ 68㸧ࢆྜᡂࡋࡓ (Scheme 22)ࠋ Scheme 22

⥆࠸࡚ࠊTBAF ࢆ⏝࠸ࡓ⣔࡛ SESe యࢆάᛶ໬ࡋࠊMeSeTs㸦໬ྜ≀ 68㸧ࢆồ㟁Ꮚ๣࡜ࡋ࡚

స⏝ࡉࡏࠊ࣊ࢸࣟࢪࢭࣞࢽࢻࡢᙧᡂࢆヨࡳࡓ (Scheme 23)ࠋ Scheme 23 ┠ⓗ≀ࡢ⏕ᡂࡣ1H-NMRࠊ㉁㔞ศᯒ࡟ࡼࡾ☜ㄆࡉࢀࡓࡶࡢࡢࠊ໬ྜ≀ࡣᚎࠎ࡟ศゎࡋ⢾ࡢ ࢪࢭࣞࢽࢻ70 ࡜ࢪ࣓ࢳࣝࢪࢭࣞࢽࢻ࡜ࡢ஧✀㢮ࡢ࣍ࣔࢪࢭࣞࢽࢻ࡟ศゎࡋ࡚ࡋࡲࡗࡓࠋࡇ ࢀࡣࠊഃ㙐ࡢ࣓ࢳࣝᇶ࡟ࡼࡾእഃࡢࢭࣞࣥཎᏊࡢ㟁Ꮚᐦᗘࡀୖ᪼ࡋSe-Se ⤖ྜࡀ୙Ᏻᐃ໬ࡍ ࡿࡇ࡜࡛㉳ࡁࡓࡶࡢ࡜⪃࠼ࡽࢀࡓࠋഃ㙐ࡢ⨨᥮ᇶࢆኚ᭦ࡍࡿࡇ࡜࡛ᙧᡂࡍࡿࢪࢭࣞࢽࢻࡢ Ᏻᐃᛶࢆྥୖ࡛ࡁࡿྍ⬟ᛶࡣ⪃࠼ࡽࢀࡓࡀࠊࡇࡇ࡛ࠊࢪࢭࣞࢽࢻᆺࡢྜᡂࡣ᩿ᛕࡍࡿࡇ࡜

(41)

࡜ࡋࡓࠋ ⥆࠸࡚ࠊC2 ᆺồ㟁Ꮚ๣ࢆ㛤Ⓨࡍࡿࡇ࡜ࡋࡓ (Scheme 24)ࠋ2-ࣈ࢚ࣟࣔࢱࣀ࣮ࣝࢆฟⓎཎᩱ࡜ ࡋ࣓ࢳࣝࢭࣞࣀ໬ࢆヨࡳࡓࡀࠊ⏕ᡂࡋࡓ2-࣓ࢳࣝࢭࣞࣀ࢚ࢱࣀ࣮ࣝ 71 ࡣపἛⅬ࡛࠶ࡾࠊ⃰ ⦰ࠊ஝⇱ࡢ᧯సࡀᅔ㞴࡜࡞ࡗࡓࠋศᏊ㔞ࡢቑຍ࡟ࡼࡾἛⅬࡀୖ᪼ࡋ≀㉁ࡢྲྀࡾᢅ࠸ࡀᨵၿ ࡍࡿࡇ࡜ࢆᮇᚅࡋࠊ⬺㞳ᇶ࡜ࡋ࡚ࢺࢩࣝᇶࢆᑟධࡍࡿࡇ࡜ࢆヨࡳࡓࡀࠊ┠ⓗࡢࢺࢩࣝయ 72 ࡣᚓࡽࢀࡎࠊሷ⣲໬ࡉࢀࡓ໬ྜ≀73 ࢆᚓࡿࡢࡳ࡛࠶ࡗࡓࠋሷ⣲య 73 ࡶồ㟁Ꮚ๣࡜ࡋ࡚ࢭ ࣞࣀ࢔ࢽ࢜ࣥ࡜཯ᛂࡉࡏࡿࡇ࡜ࡣྍ⬟ࡔ࡜⪃࠼ࡽࢀࡓࡀࠊࡇࡢ໬ྜ≀ࡶపἛⅬ࡛ྲྀࡾᢅ࠸ ࡀᅔ㞴࡛࠶ࡾࠊࡲࡓࢪ࣓ࢳࣝࢪࢭࣞࢽࢻ࡬ࡢศゎࡶほᐹࡉࢀࡓࡓࡵࠊࡑࡢ฼⏝ࡣ᩿ᛕࡋࡓࠋ Scheme 24 ࡑࡇ࡛ྜᡂᡓ␎ࢆ❧࡚┤ࡋࠊඛ࡟⢾࡬ࣈ࢚ࣟࣔࢱࣀ࣮ࣝࢆᑟධࡋࠊࡑࡢᚋᮎ➃ࡢỈ㓟ᇶ ࢆ⬺㞳ᇶ࡟ኚ᥮ࡋࠊ᭱ᚋ࡟࣓ࢳࣝࢭࣞࣀᇶ࡛⨨᥮ࡍࡿ࡜࠸࠺᪉ἲࢆྲྀࡿࡇ࡜࡜ࡋࡓ (Scheme 25)ࠋ Scheme 25 SE ᇶ࠿ࡽࣄࢻࣟ࢟ࢩ࢚ࢳࣝᇶ࡬ࡢኚ᥮ࡣ㧗཰⋡࡛⾜࠺ࡇ࡜ࡀ࡛ࡁࡓࠋࡑࡢᚋࠊ⬺㞳ᇶ࡜ ࡋ࡚⮯⣲ࠊࢺࣜࣇ࣮ࣞࢺᇶࠊ࣓ࢩࣝᇶࠊࢺࢩࣝᇶࡢᑟධࢆヨࡳࡓࡀࠊ࠸ࡎࢀࡢሙྜࡶ཯ᛂ ࡣ」㞧࡜࡞ࡾࠊ┠ⓗ࡜ࡍࡿ໬ྜ≀ࢆ୺⏕ᡂ≀࡜ࡋ࡚ᚓࡿࡇ࡜ࡣ࡛ࡁ࡞࠿ࡗࡓࠋ ௨ୖࡢ C2 ᆺồ㟁Ꮚ๣ࡢ⤖ᯝ࠿ࡽࢭࣞࣥཎᏊ࠿ࡽE఩࡟ᙜࡓࡿ఩⨨࡟⬺㞳ᛶࡢ㧗࠸ᐁ⬟ᇶ

(42)

- 40 - ࢆᑟධࡍࡿࡇ࡜ࡣᅔ㞴࡛࠶ࡾࠊᑟධ࡛ࡁࡓ࡜ࡋ࡚ࡶ໬ྜ≀ࡢᏳᐃᛶࡣపࡃྲྀࡾᢅ࠸ࡀᅔ㞴 ࡟࡞ࡿࡇ࡜ࡀศ࠿ࡗࡓࠋ ࢪࢭࣞࢽࢻᆺࠊC2 ᆺࡢ⤖ᯝࢆ㋃ࡲ࠼ࠊ⥆࠸࡚ C3 ᆺࢆྜᡂࡍࡿࡇ࡜࡜ࡋࡓ (Scheme 26)ࠋ Scheme 26 1,3-ࣅࢫࢺࢩࣝ࢜࢟ࢩࣉࣟࣃࣥࢆཎᩱ࡜ࡋ࡚ࢪ࣓ࢳࣝࢪࢭࣞࢽࢻཬࡧỈ⣲໬࣍࢘⣲ࢼࢺ ࣒ࣜ࢘ࢆస⏝ࡉࡏࡿࡇ࡜࡛໬ྜ≀77 ࢆᚓࡿࡇ࡜ࡀ࡛ࡁࡓࠋࡇࡢ໬ྜ≀ 77 ࡣ-20 ºC ࡛ࡢ㛗ᮇ ಖᏑ࡛ࡣ୍㒊ศゎࡀ࠶ࡿࡶࡢࡢࠊἛⅬࡣ㧗ࡃẚ㍑ⓗྲྀࡾᢅ࠸᫆࠸໬ྜ≀࡛࠶ࡗࡓࠋ Scheme 27 TBAF ࢆ⏝࠸ࡓ⣔࡛ SESe యࢆάᛶ໬ࡋࠊ໬ྜ≀ 77 ࢆồ㟁Ꮚ๣࡜ࡋ࡚཯ᛂࢆ⾜ࡗࡓ࡜ࡇࢁࠊ ཰⋡ 83%࡛࣓ࢳࣝࢭࣞࣀࣉࣟࣆࣝᇶࢆᑟධࡍࡿࡇ࡜ࡀ࡛ࡁࡓࠋࡇࡢࡼ࠺࡟ࡋ࡚ࠊ୍ศᏊෆ ࡟2 ಶࡢࢭࣞࣥཎᏊࢆᣢࡘ⢾ࡢྜᡂ࡟ᡂຌࡋࡓ (Scheme 27)ࠋ

(43)

➨ ➨㸱⠇ ࢺࣜࢭࣞࣀࢩ࢔ࣜࣝD(2-6)࢞ࣛࢡࢺ࣮ࢫࡢྜᡂ ⥆࠸࡚ࠊ୍ศᏊෆ࡟3 ಶࡢࢭࣞࣥཎᏊࢆ᭷ࡍࡿࢺࣜࢭࣞࣀࢩ࢔ࣜࣝD(2-6)࢞ࣛࢡࢺ࣮ࢫࡢ ྜᡂࢆ⾜ࡗࡓࠋ➨2 ⠇࡛ྜᡂࡋࡓࢩ࢔ࣜࣝD(2-6)࢞ࣛࢡࢺ࣮ࢫࡢ SESe ࢢࣜࢥࢩࢻయ 66 ࢆฟ Ⓨཎᩱ࡜ࡋ࡚ࠊTBAF ࡟ࡼࡾ SE ᇶࢆάᛶࡋ࣓ࢳࣝࢭࣞࣀᇶࢆ᭷ࡍࡿồ㟁Ꮚ๣ 78 ࡜཯ᛂࡉࡏ ࡿࡇ࡜࡛ࠊࢺࣜࢭࣞࣀ໬ྜ≀79 ࢆ཰⋡ 82%࡛ྜᡂࡋࡓ (Scheme 28)ࠋ Scheme 28 ᭱ᚋ࡟ࠊ࢔ࢩࣝ⣔ಖㆤᇶཬࡧࢩ࢔ࣝ㓟ṧᇶࡢ࣓ࢳ࢚ࣝࢫࢸࣝࢆຍỈศゎࡋࠊ཰⋡ 86%࡛ ࢺࣜࢭࣞࣀࢩ࢔ࣜࣝD(2-6)࢞ࣛࢡࢺ࣮ࢫ 80 ࡢྜᡂ࡟ᡂຌࡋࡓࠋ ࡇࡢ໬ྜ≀ࡣ⌧ᅾࠊඹྠ◊✲ඛ࡟࡚ࠊศᏊ㔞42 kDa ࡢ኱ᆺ⺮ⓑ㉁ࣄࢺ⏤᮶ࢩ࢔ࣜࢲ࣮ࢮ Neu 233࡜ࡢᵓ㐀ゎᯒ࡬㐺⏝୰࡛࠶ࡿࠋࡇࡢ⺮ⓑ㉁࡜ࡢ❧యᵓ㐀Ỵᐃࡀ㐩ᡂࡉࢀࡿࡇ࡜࡛ࢭ ࣞࣀ໬⢾㙐ࢆ⏝࠸ࡿX ⥺ඹ⤖ᬗᵓ㐀ゎᯒࡢ᭷⏝ᛶࡀ㧗ࡲࡿࡶࡢ࡜⪃࠼࡚࠸ࡿࠋ

33_{L. M. G. Chavas, C. Tringali, P. Fusi, B. Venerando, G. Tettamanti, R. Kato, E. Monti, S.}

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- 42 - ⥲ ⥲ᣓ ᪂ࡓ࡟ࠊ┤㙐ࢭࣞࣀ࢔ࢭࢱ࣮࡛ࣝ࠶ࡿBOMSeR (R=Me,Ph,SE)ࢆồ᰾๣࡜ࡋ࡚㛤Ⓨࡋࠊࡇ ࢀࢆࢢࣜࢥࢩࣝ࢖࣑ࢹ࣮ࢺయ࡜ࣝ࢖ࢫ㓟Ꮡᅾୗ࡛཯ᛂࡉࡏࡿࡇ࡜࡛ࠊ༢⢾࠿ࡽᅄ⢾ࡲ࡛ࡢ ⢾㙐ࡢ㑏ඖᮎ➃࡟ 70%௨ୖࡢ཰⋡࡛࢔ࣝ࢟ࣝࢭࣞࣀᇶࢆ❧య㑅ᢥⓗ࡟ᑟධࡍࡿࡇ࡜࡟ᡂຌ ࡋࡓࠋᮏᡭἲࡣࠊ୍⯡ⓗ࡞ࢢࣜࢥࢩࣝ໬ࡢ཯ᛂ᮲௳࡟࡚ࢭࣞࣀ໬⢾㙐ࢆྜᡂ࡛ࡁࡿࡓࡵࠊ ᵝࠎ࡞ྜᡂ⢾㙐࡬ࡢᛂ⏝ࡀྍ⬟࡛࠶ࡾࠊࡉࡽ࡟ࠊྜᡂ⤊┙࡛ࡶࢭࣞࣥࢆᑟධྍ⬟࡞ඃࢀࡓ ᪉ἲ࡛࠶ࡿ࡜ࡇ࡜ࡀ☜ㄆࡉࢀࡓࠋ ࡲࡓࠊSESe ᇶࢆ TBAF ࡟ࡼࡾάᛶ໬ࡋࠊ3-࣓ࢳࣝࢭࣞࣀࣉࣟࣆࣝࢺࢩ࣮ࣞࢺࢆồ㟁Ꮚ๣ ࡜ࡋ࡚཯ᛂࡉࡏࡿࡇ࡜࡛ࠊࢭࣞࣥ୕⨨᥮ࢩ࢔ࣜࣝD(2-6)࢞ࣛࢡࢺ̿ࢫࡢྜᡂ࡟ᡂຌࡋࡓࠋࡇ ࡕࡽࡣ௒ᚋࠊศᏊ㔞42 kDa ࡢࢩ࢔ࣜࢲ࣮ࢮ Neu2 ࡜ࡢඹ⤖ᬗ໬ࠊᵓ㐀ゎᯒࢆ⾜࠸ࠊࢭࣞࣥ ከ⨨᥮⢾㙐ࡢX ⥺⤖ᬗᵓ㐀ゎᯒ࡟࠾ࡅࡿ᭷⏝ᛶࡢ᳨ドࢆ⾜ࡗ࡚࠸ࡃࠋ

(45)

ࡲ ࡲ࡜ࡵ ㏆ᖺࡢ⢾㙐⛉Ꮫࡢ₻ὶࡣࠊศᏊ⏕≀Ꮫⓗ࡞࢔ࣉ࣮ࣟࢳ࡟ࡼࡿ⢾㙐ࡢ᭷ࡍࡿ⏕࿨ᶵ⬟ࡢゎ ᫂࡟࠶ࡿ࡜ᛮࢃࢀࠊᵝࠎ࡞⢾㙐ࣉ࣮ࣟࣈࢆ⏝࠸ࡓ◊✲ࠊ౛࠼ࡤ⺯ගᶆ㆑໬⢾⬡㉁ࢆ⏝࠸ࡓ ୍ศᏊ㏣㊧ἲ࡟ࡼࡿ⭷ୖ࡛ࡢ⢾⬡㉁ࡢືⓗ࡞᣺ࡿ⯙࠸ࡢ◊✲ࡸࠊᏳᐃྠ఩యᶆ㆑ࡋࡓ⢾ࢱ ࣥࣃࢡ㉁ࢆ⏝࠸ࡓ㉸㧗☢ሙ NMR ࡟ࡼࡿࢥࣥࣇ࢛࣓࣮ࢩࣙࣥゎᯒࡢ◊✲࡞࡝ࡀ⬮ගࢆᾎࡧ ࡚࠸ࡿࠋᮏ◊✲࡛᭷⏝ᛶࢆ᳨ドࡋࡓࢭࣞࣥᶆ㆑⢾㙐ࢆ⏝࠸ࡓ MAD ἲ࡟ࡼࡿ⢾㙐-⺮ⓑ㉁」 ྜయࡢ X ⥺⤖ᬗᵓ㐀ゎᯒࡣࠊࡑࢀࡽᡭἲ࡜ྠᵝ࡟㔜せ࡞ᢏ⾡࡜࡞ࡾ࠺ࡿ࡜⪃࠼ࡽࢀࠊ⏕࿨ ⌧㇟ࡢゎ᫂࡟ᐤ୚ࡋࠊ⸆Ꮫศ㔝࡟࠾ࡅࡿࢻࣛࢵࢢࢹࢨ࢖ࣥ࡬ࡢ᭷⏝࡞᝟ሗࡲ࡛୚࠼ࡿ࡜⪃ ࠼ࡽࢀࡿࠋ ᮏ◊✲୰࡛ᚓࡽࢀࡓ◊✲⤖ᯝࡣࠊ➨ 1 㒊࡛㛤Ⓨࡋࡓࢭࣞࣥᶆ㆑⢾౪୚యࠊཷᐜయ࡜ࠊࡑ ࢀࡽࢆ⏝࠸ࡓࢢࣜࢥࢩࣝ໬ࡢ᳨ウ࡟㛵ࡋ࡚ࡣࠊ௒ᚋࡢࢭࣞࣥᶆ㆑໬ከ⢾ࡢᵓ⠏ࢆ⾜࠺㝿࡟ ᭷⏝࡞᝟ሗࢆ୚࠼ࡿࡶࡢ࡛࠶ࡾࠊ➨ 2 㒊࡛㛤Ⓨࡋࡓ᪂つࢭࣞࣀࢢࣜࢥࢩࢻྜᡂἲ࡟㛵ࡋ࡚ ࡣࠊᵝࠎ࡞⢾㙐࡬ࡢ⡆౽࡞ࢭࣞࣥᶆ㆑ࢆྍ⬟࡟ࡍࡿࡶࡢ࡛࠶ࡿࠋᮏ◊✲ࢆ㏻ࡌ࡚ᚓࡽࢀࡓ ᡂᯝࢆᇶ࡟ࠊከ✀ከᵝ࡞ࢭࣞࣀࢢࣜࢥࢩࢻࣛ࢖ࣈ࣮ࣛࣜࢆᵓ⠏ࡍࡿࡇ࡜࡛ࠊ㎿㏿࡞⢾㙐-⺮ ⓑ㉁」ྜయࡢ❧యᵓ㐀ゎᯒࡀྍ⬟࡟࡞ࡿ࡜⪃࠼ࡽࢀࡿࠋ ௒ᚋࡣࠊࢭࣞࣥᶆ㆑⢾㙐ࢆ⏝࠸ࡓ⺮ⓑ㉁」ྜయࡢ⤖ᬗᵓ㐀ゎᯒࡢᐇ᪋౛ࢆቑࡸࡋࠊᮏᡭ ἲࢆࡼࡾᙉຊ࡞ࡶࡢ࡜ࡋ࡚ࠊ⢾㙐ࡢ㛵ࢃࡿ⏕࿨⌧㇟ࡢゎ᫂࡟㈉⊩ࡋ࡚࠸ࡁࡓ࠸ࠋ

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- 44 -

ᐇ

ᐇ㦂ࡢ㒊

ᮏㄽᩥ࡟࠾࠸࡚඲࡚ࡢᐇ㦂ࡣ௨ୗࡢᡭ㡰ࠊჾලཬࡧ⿦⨨ࢆ౑⏝ࡋࡓࠋࡲࡓࠊグ㍕࡟ࡘ࠸ ࡚ࡶ௨ୗࡢ㏻ࡾ⤫୍ࡋࡓࠋ

཯ᛂ⁐፹ࡣ࠶ࡽ࠿ࡌࡵMS3ÅࠊMS4ÅࠊMS AW-300 (Wako chemical)࡟࡚஝⇱ࡋࡓࡶࡢࢆ౑

⏝ࡋࡓࠋ཯ᛂ࡟⏝࠸ࡓ஝⇱๣ࡣ300 °C ࡟࡚ 2 ᫬㛫άᛶ໬ࡋ౑⏝ࡋࡓࠋ⬺Ẽ᧯సࡀᚲせ࡞⁐

፹࡟ࡘ࠸࡚ࡣࠊῶᅽୗࠊ20 ศ㛫ࢯࢽࢣ࣮ࢩࣙࣥࢆ⾜ࡗࡓᚋ࡟ࠊ࢔ࣝࢦࣥࣂࣈࣜࣥࢢࢆ 30 ศ

㛫⾜࠸཯ᛂ࡟⏝࠸ࡓࠋ㉸㡢Ἴ↷ᑕ᮲௳࡛ࡢ཯ᛂࡣUS CLEANER USD-4R (AS ONE)ࢆ⏝࠸࡚

⾜ࡗࡓࠋTLC ศᯒ࡟ࡣ TLC plate silica gel 60F254 (Merck)ࢆ౑⏝ࡋࠊ᳨ฟࡣ UV ྾཰ (254 nm)

ཬࡧⓎⰍヨ⸆ (10% H2SO4 in EtOH, Phosphomolybdic acid solution 5 wt. % in ethanol, Ninhydrin

reagent)ࢆ⏝࠸ࡓࠋ࣒࢝ࣛࢡ࣐ࣟࢺࢢࣛࣇ࢕࣮ࡣ Silica gel (Fuji Silysia, 80 mesh and 300 mesh) ࡲࡓࡣࠊSephadex (Pharamacia, LH-20)ࢆ⏝࠸ࡓࠋ࡞࠾ TLC ࡢᒎ㛤⁐፹ཬࡧ࣒࢝ࣛࢡ࣐ࣟࢺ

ࢢࣛࣇ࢕࣮ࡢ⁐ฟ⁐፹ࡣ (v/v)࡟♧ࡋࡓࠋ1_{H-NMR ࢫ࣌ࢡࢺࣝࠊ}13_{C-NMR ࢫ࣌ࢡࢺࣝཬࡧ}

77_{Se-NMR ࢫ࣌ࢡࢺࣝࡣ JEOL ECX400 (400MHz)ࠊJEOL ECA500 (500MHz)ࠊJEOL ECA600}

(600MHz)ཬࡧ Bruker Avance III 500 (500MHz)ࢆ⏝࠸ࡓࠋࢣ࣑࢝ࣝࢩࣇࢺ್ࡣࠊ1_{H NMRࠊ}13_C

NMR ࡟ࡘ࠸࡚ࡣෆ㒊ᶆ‽≀㉁ (tetramethylsilane)࡟ᑐࡍࡿG್ (ppm)࡛♧ࡋࠊ77_{Se NMR ࡟ࡘ}

࠸࡚ࡣእ㒊ᶆ‽࡟ᑐࡍࡿG್ (ppm)࡛♧ࡋࡓࠋ᪕ගᗘࡣ Horiba High Sensitive Polarimeter SEPA-300 ࢆ⏝࠸࡚ ᐃࡋࠊHRMS ࢫ࣌ࢡࢺࣝ (ESI-TOF)ࡣ Bruker Daltonics micrOTOF (ESI-TOF) mass spectrometer ࢆ⏝࠸࡚ positive-ion ࣮ࣔࢻࠊࡲࡓࡣ negative-ion ࣮ࣔࢻ࡛ ᐃ ࡋࡓࠋ

(47)

17

2-(Trimethylsilyl)ethyl 2,3-di-O-benzoyl-6-bromo-6-deoxy-E-D-galactopyranoside (17): Ar 㞺ᅖ

Ẽୗ࡟࡚ࠊ໬ྜ≀16 (384 mg, 787 Pmol)ࢆ pyridine (5.3 mL)࡟⁐࠿ࡋࠊtriphenylphosphine (310 mg, 1.18 mmol)ཬࡧ carbontetrabromide (262 mg, 790 Pmol)ࢆ 0 °C ࡟࡚ຍ࠼ 10 ศᨩᢾࡋࡓࠋࡑ ࡢᚋࠊ65 °C ࡟᪼ ࡋࠊ1 ᫬㛫ᨩᢾࡋࡓࠋ཯ᛂ⤊஢ࢆ TLC (EtOAc/toluene = 1/5)࡛☜ㄆᚋࠊ MeOH ࢆຍ࠼཯ᛂࢆ೵Ṇࡋࠊtoluene ඹἛࢆ⾜࡞ࡗࡓᚋࠊṧ´ࢆࣇࣛࢵࢩࣗࢩࣜ࢝ࢤࣝ࢝ࣛ ࣒ࢡ࣐ࣟࢺࢢࣛࣇ࢕࣮ (EtOAc/toluene = 1/20)࡛⢭〇ࡋࠊ໬ྜ≀ 17 ࢆ (379 mg, 87 %)ⓑⰍἻ ≧⢊ᮎ࡜ࡋ࡚ᚓࡓࠋ[D]D=+63.8° (c=1.1, CHCl3); 1H NMR (400 MHz, CDCl3):G 7.99-7.36 (m, 10 H, Ph), 5.69 (dd, 1 H, J1,2 = 7.8 Hz, J2,3 = 10.5 Hz, H-2), 5.32 (dd, 1 H, J3,4 = 3.2 Hz, H-3), 4.72 (d, 1 H, H-1), 4.47 (dd, 1 H, J4,OH = 6.0 Hz, H-4), 4.07 (m, 1 H, TMSCH2CH2), 3.93 (t, 1 H, J5,6a = J5,6b = 6.9 Hz, H-5), 3.69-3.57 (m, 3 H, H-6a, H-6b, TMSCH2CH2), 2.25 (d, 1 H, OH), 1.00-0.81 (m, 2 H, TMSCH2), -0.07 (s, 9 H, TMS); 13C NMR (100 MHz, CDCl3): G 165.8, 165.3, 133.5, 133.1, 129.9, 129.7 128.9, 128.5, 128.3, 100.8, 74.6, 74.3, 69.5, 67.6, 67.3, 28.9, 17.9, -1.5; HRMS: m/z calcd for C25H31BrO7SiNa+: 573.0915 [M+Na]+; found:573.0912.

18

2-(Trimethylsilyl)ethyl 2,3-di-O-benzoyl-6-deoxy-6-(p-methylbenzoylseleno)-E-D-galactopyrano side (18): Ar 㞺ᅖẼୗ࡟࡚ࠊ໬ྜ≀ 17 (5.61 g, 10.2 mmol)ཬࡧ p-methylselenobenzoic anhydride (໬ྜ≀ 11) (4.12 g, 13.0 mmol)ࢆ⬺Ẽࡋࡓ DMF (67 mL)࡟⁐࠿ࡋࠊN,N-diisopropylethylamine (2.2 mL, 13.0 mmol)ཬࡧ piperidine (1.3 mL, 13.0 mmol)ࢆᐊ ࡟࡚ຍ࠼ࠊ100 °C ࡟࡚ 45 ศ㛫ᨩ ᢾࡋࡓࠋ཯ᛂ⤊஢ࢆTLC (EtOAc/hexane = 1/2)࡛☜ㄆᚋࠊEtOAc ࡛ 2 ᅇᢳฟࠊὙί (2M ሷ㓟ࠊ

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- 46 - 㣬࿴Ⅳ㓟Ỉ⣲ࢼࢺ࣒ࣜ࢘Ỉ⁐ᾮࠊ㣬࿴㣗ሷỈ)ࠊ஝⇱ (↓Ỉ◲㓟ࢼࢺ࣒ࣜ࢘)ࠊ⁐፹␃ཤᚋࠊ ṧ ´ ࢆ ࣇ ࣛ ࢵ ࢩ ࣗ ࢩ ࣜ ࢝ ࢤ ࣝ ࢝ ࣛ ࣒ ࢡ ࣟ ࣐ ࢺ ࢢ ࣛ ࣇ ࢕ ࣮ (EtOAc/hexane = 1/6, EtOAc/toluene = 1/15)࡛⢭〇ࡋࠊ໬ྜ≀ 18 (6.52 g, 97 %)ࢆⓑⰍἻ≧⢊ᮎ࡜ࡋ࡚ᚓࡓࠋ [D]D=+36.8° (c=0.2, CHCl3); 1H NMR (400 MHz, CDCl3): G 7.99-7.47 (m, 14 H, Ar), 5.72 (dd, 1 H, J1,2 = 8.1 Hz, J2,3 = 10.4 Hz, H-2), 5.30 (dd, 1 H, J3,4 = 3.2 Hz, H-3), 4.70 (d, 1 H, H-1), 4.36 (dd, 1 H, J4,OH = 6.0 Hz, H-4), 4.06 (m, 1 H, TMSCH2CH2), 3.85 (t, 1 H, J5,6a = J5,6b = 7.3 Hz, H-5), 3.63

(m, 1 H, TMSCH2CH2), 3.50-3.39 (m, 2 H, H-6a, H-6b), 2.59 (d, 1 H, OH), 2.41 (s, 3 H, ArCH3),

1.00-0.84 (m, 2 H, TMSCH2), -0.07 (s, 9 H, TMS); 13C NMR (100 MHz, CDCl3): G 194.3, 165.9,

165.3, 145.1, 136.0, 133.3, 133.0, 129.9, 129.7, 129.5, 129.1, 129.0, 128.4, 128.2, 127.4, 100.7, 74.5, 69.7, 68.4, 67.4, 24.5, 21.7, 17.9, -1.5; 77Se NMR (75 MHz, CDCl3): G 530.7; HRMS: m/z calcd for

C33H38O8SeSiNa+: 693.1393 [M+Na]+; found: 693.1390.

19

2-(Trimethylsilyl)ethyl 4-O-acetyl-2,3-di-O-benzoyl-6-deoxy-6-(p-methylbenzoyl)seleno-E-D-ga lactopyranosid(19): Ar 㞺ᅖẼୗ࡟࡚ࠊ໬ྜ≀ 18 (5.48 g, 8.18 mmol)ࢆ pyridine (40.9 mL) ࡟⁐࠿ࡋࠊacetic anhydride (3.9 mL, 41.3 mmol)ࢆຍ࠼ࠊᐊ ࡟࡚ 25 ᫬㛫ᨩᢾࡋࡓࠋ཯ᛂ⤊ ஢ࢆ TLC (EtOAc/hexane = 1/3, ஧ᅇᒎ㛤)࡛☜ㄆᚋࠊMeOH ࢆຍ࠼ࡓᚋࠊtoluene ඹἛࢆ⾜

࡞࠸ࠊṧ´ࢆEtOAc ࡛ 2 ᅇᢳฟࡋࠊὙί (2M ሷ㓟ࠊỈࠊ㣬࿴Ⅳ㓟Ỉ⣲ࢼࢺ࣒ࣜ࢘Ỉ⁐ᾮࠊ 㣬࿴㣗ሷỈ)ࠊ஝⇱ (↓Ỉ◲㓟ࢼࢺ࣒ࣜ࢘)ࠊ⁐፹␃ཤᚋࡢṧ´ࢆࣇࣛࢵࢩࣗࢩࣜ࢝ࢤࣝ࢝ࣛ ࣒ࢡ࣐ࣟࢺࢢࣛࣇ࢕࣮ (EtOAc/hexane = 1/8)࡛⢭〇ࡋࠊ໬ྜ≀ 19 (5.60 g, 96 %)ࢆⓑⰍἻ ≧⢊ᮎ࡜ࡋ࡚ᚓࡓࠋ[D]D=+30.8° (c=1.3, CHCl3); 1H NMR (400 MHz, CDCl3): G 7.97-7.25 (m, 14 H, Ar), 5.76 (d, 1H, J3,4 = 3.3 Hz, H-4), 5.67 (dd, 1H, J1,2 = 7.8 Hz, J2,3 = 10.5 Hz, H-2), 5.40 (dd, 1H, H-3), 4.73 (d, 1H, H-1), 4.07 (m, 1H, TMSCH2CH2), 3.97 (t, 1H,

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J5,6a = J5,6b = 7.3 Hz, H-5), 3.64 (m, 1H, TMSCH2CH2), 3.36–3.25 (m, 2H, H-6a, H-6b), 2. 41 (s, 3H, ArCH3), 2.16 (s, 3H, Ac), 1.02–0.85 (m, 2H, TMSCH2), 0.07 (s, 9H, TMS); 13C NMR (100 MHz, CDCl3): G 193.0, 170.1, 165.5, 165.2, 145.0, 135.9, 133.2, 133.0, 129.7, 129.6, 129.5, 129.0, 128.3, 128.2, 127.3, 100.7, 73.2, 72.1, 69.6, 69.1, 67.7, 60.3, 24.4, 21.7, 20.6, 17.9, 14.1,1.5; 77_{Se NMR (75 MHz, CDCl} 3): G 495.6; HRMS: m/z calcd for C33H40O9

SeSiNa+_{: 735.1504 [M+Na]}+_{; found: 735.1504.}

20

2-(Trimethylsilyl)ethyl 4-O-acetyl-2,3-di-O-benzoyl-6-deoxy-6-methylseleno-E-D-galactopyran oside(20): Ar 㞺ᅖẼୗ࡟࡚ࠊ໬ྜ≀ 19 (308 mg, 432 Pmol)ཬࡧ cesium carbonate (289 mg, 885 Pmol)ࢆ⬺Ẽࡋࡓ DMF (8.7 mL)࡟⁐࠿ࡋࠊmethyl hydrazine (34.2 PL, 650 Pmol)ཬࡧ m ethyl iodide (53.9 PL, 865 Pmol)ࢆຍ࠼ࠊᐊ ࡟࡚ᨩᢾࡋࡓࠋ཯ᛂ㏣㊧ࢆ TLC (EtOAc/tolue ne = 1/10)࡟࡚⾜࠸ࠊ཯ᛂ㛤ጞ࠿ࡽ 2 ᫬㛫ᚋ࡟ࠊmethyl hydrazine (34.2 PL, 650 Pmol)ཬࡧ methyl iodide (53.9 PL, 865 Pmol)ࢆ㏣ຍࡋࠊ཯ᛂ㛤ጞ࠿ࡽ 17 ᫬㛫ᚋࠊ཯ᛂ⤊஢ࢆ☜ㄆࡋࡓࠋ EtOAc ࡛ 2 ᅇᢳฟࡋࠊὙί(2M ሷ㓟ࠊỈࠊ㣬࿴Ⅳ㓟Ỉ⣲ࢼࢺ࣒ࣜ࢘Ỉ⁐ᾮࠊ㣬࿴㣗ሷỈ)ࠊ ஝⇱ (↓Ỉ◲㓟ࢼࢺ࣒ࣜ࢘)ࠊ⃰⦰ᚋࡢṧ´ࢆࣇࣛࢵࢩࣗࢩࣜ࢝ࢤ࣒ࣝ࢝ࣛࢡ࣐ࣟࢺࢢࣛࣇ ࢕࣮ (EtOAc/hexane = 1/3)࡛⢭〇ࡋࠊ໬ྜ≀ 20 (206 mg, 78 %)ࢆⓑⰍᅛయ࡜ࡋ࡚ᚓࡓࠋ[D] D=+31.2° (c=0.5, CHCl3); 1H NMR (400 MHz, CDCl3): G 7.98-7.33 (m, 10 H, Ph), 5.69-5.6 4 (m, 2 H, H-4, H-2), 5.41 (dd, 1 H, J3,4 = 2.8 Hz, J2,3 = 10.5 Hz, H-3), 4.74 (d, 1 H, J1, 2 = 8.2 Hz, H-1), 4.06 (m, 1 H, TMSCH2CH2), 3.98 (m, 1 H, J5,6b = 6.0 Hz, J5,6a = 7.8 H z, H-5), 3.64 (m, 1 H, TMSCH2CH2), 2.84 (dd, 1 H, Jgem = 12.8 Hz, H-6a), 2.60 (dd, 1 H, H-6b), 2.14 (s, 3 H, Ac), 2.09 (s, 3 H, 3 H, SeCH3); 13C NMR (125 MHz, CDCl3): G165. 5, 165.2, 165.2, 164.8, 160.7, 133.5, 133.5, 133), 1.02-0.85 (m, 2 H, TMSCH2), -0.07 (s, 9

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- 48 - H, TMS); 13_{C NMR (100 MHz, CDCl}

3) G 170.2, 165.6, 165.2, 133.3, 133.1, 132.3, 129.7, 1

29.6, 129.0, 128.4, 128.4, 128.3, 100.8, 74.6, 72.1, 69.6, 69.3, 67.7, 24.6, 20.6, 17.9, 5.6, -1. 5; 77_{Se NMR (75 MHz, CDCl}

3): G 73.2; HRMS: m/z calcd for C28H36O8SeSiNa+: 631.1237

[M+Na]+; found: 631.1237.

ࡲࡓࠊୖグࡢ཯ᛂ⣔࡟࠾࠸࡚๪⏕ᡂ≀21 ࢆ㯤Ⰽ⢓ᛶᾮయ࡜ࡋ࡚ᚓࡓࠋ

21

Bis-{6-[2-(trimethylsilyl)ethyl 4-O-acetyl-6-deoxy-2,3-di-O-benzoyl-E-D-galactopyranosyl]} dis elenide (21): [D]D=+95.2° (c=1.9, CHCl3); 1H NMR (400 MHz, CDCl3) G7.97-7.33 (m, 20

H, Ar), 5.74 (d, 2 H, J3,4 = 2.8 Hz, H-4), 5.69 (dd, 2 H, J1,2 = 7.8 Hz, J2,3 = 10.6 Hz,

H-2), 5.47 (d, 2 H, H-3), 4.81 (d, 2 H, H-1), 4.12-4.05 (m, 4 H, H-5, TMSCH2CH2), 3.69-3.6

2 (m, 2 H, TMSCH2CH2), 3.27 (dd, 2 H, J5,6a = 8.3 Hz, Jgem = 12.8 Hz, H-6a), 3.02 (dd,

2 H, J5,6b = 5.5 Hz, H-6b), 2.16 (s, 6 H, OAc), 1.03-0.85 (m, 4 H, TMSCH2CH2), -0.07 (s, 18 H, TMS); 13_{C NMR (100 MHz, CDCl} 3) G170.2, 165.6, 165.2, 133.3, 133.1, 129.7, 129. 7, 129.5, 128.9, 128.4, 128.3, 100.8, 73.3, 72.2, 69.6, 69.2, 67.8, 29.3, 20.7, 17.9, -1.5; 77_Se NMR (75 MHz, CDCl3) G302.8; HRMS: m/z calcd for C54H66O16Se2Si2Na+: 1209.2118 [M+ Na]+_{; found: 1209.2118.} 22 4-O-Acetyl-2,3-di-O-benzoyl-6-deoxy-6-methylseleno-E-D-galactopyranose (22): Ar 㞺ᅖẼୗ

糖鎖－蛋白質複合体のX線結晶構造解析のためのセレン標識糖鎖プローブの開発

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