1988 Fiscal Year Final Research Report Summary
Studies on the synthesis of optically active glycosidase inhibitors
| Project/Area Number |
62570957
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Chemical pharmacy
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| Research Institution | National Institute of Radiological Sciences |
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Principal Investigator |
NOBUO IKOTA National Institute of Radiological Sciences, 薬理化学研究部, 主任研究官 (80159649)
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| Project Period (FY) |
1987 – 1988
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| Keywords | optically active compound / glycosidase inhibitor / immunomodulator / (S)-pyroglutamic acid / swainsonine / Geissmann-Waiss lactone / AI-77-B / 立体選択的合成 |
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| Research Abstract |
1. Synthesis of optically active 3,4-dihydroxy-2-hydroxymethylpyrrolidines(1) trihydroxylated pyrrolidines(1), which possess potent alpha-glycosidase or alpha-mannosidase inhibitory activities, were synthesized stereoselectively from (S)- and (R)-glutamic acid, or D-ribonolactone.
2. Synthesis of (-)-swainsonine and its stereoisomers Stereoselective allylation of the aldehyde(2) derived from trihydroxylated pyrrolidine prepared as mentioned in section 1, followed by hydroboration-oxidation and subsequent mesylation and deprotection gave (-)-swainsonine and its stereoisomers in moderate yields.
3. Synthesis of Geissmann-Waiss lactone(6) Birch reduction of a compound 4 afforded a compound 5, which was terated with BH_3-Me_2S followed by introduction of nitrile group in the primary hydroxy group and conversion into carboxyl group, and subsequent Mitusnobu reaction to invert a stereochemistry of the secondary hydroxy group and lactonization gave 6 in good yield.
4. Synthesis of (2S,3S,4S)-4-amino-2,3-dihydroxyhexanedioic acid derivative(8) cis-Dihydroxylation of unsaturated lactam(7) derived from (R)-pyroglutamic acid, followed by C-1 unit introduction(nitrile group) to primary hydroxyl group, and subsequent hydrolysis by base and ethanolic hydrogen chloride gave 8, which is a component of AI-77-B(gastroprotective substance).
KA
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