1995 Fiscal Year Final Research Report Summary
A Steroselective Synthesis of Sialic Acid Derivatives Suitable for Glycosidation Reaction
| Project/Area Number |
06672111
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Chemical pharmacy
|
|---|
| Research Institution | Teikyo University |
|---|
Principal Investigator |
IIMORI Takamasa Teikyo University, Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (90246025)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Hideyo Teikyo University, Faculty of Pharmaceutical Sciences, Research Associate, 薬学部, 助手 (10266348)
OTAKE Hiro Teikyo University, Faculty of Pharmaceutical Sciences, Research Associate, 薬学部, 助手 (50256054)
|
|---|
| Project Period (FY) |
1994 – 1995
|
| Keywords | Sialic acid / Nitric oxide / Stereoselective synthesis / Isoxazoline / Glycosylation |
|---|
| Research Abstract |
Sialylation in high yield with high stereoselecivity is known to be difficult, because the carboxyl group located at the anomeric position in sialic acid interupts glycosidic bond formation by its electric and steric factors. From this point of view, I designed a sialic acid derivative suitable for glycosidation. Employing a hydroxymethyl group as a precursor of the carboxyl group, it may be possible to prevent these negative factors and to form glycosidec bond smoothly. After glycosidation, regeneration of carbosyl function completes two-step sialylation. The purpose of this research is a development of an efficient synthesis of the sialic acid derivative having hydroxymethyl group that can be used for the glycosidation reaction.
I investigated a synthetic route to sialic acid and its derivatives from glucose by using nitrile oxide cycloaddition reaction as a key step. Considering inside alkoxy effect, an appropriate olefinic compound prepared from glucose reacts with nitric oxide to afford a key intermediate in which functionality and stereochemisry is correctly arranged for sialic acid synthesis. In fact, the desired isoxazoline derivative was obtained in high yield. The conversion of this intermediate into the sialic acid derivative was achieved by reductive cleavage of isoxazoline, introduction of acetamido group, and cyclization to pyranose sequentially. Sialic acid itself was also obtained by oxidation of hydroxymethyl group into carboxyl group.
Moreover, I also studied on the glycosidation reaction of the appropriately protected hydroxymethyl derivative that was considered as a suitable for glycosyl donor and found a vary promising result. Generally glucal formation is an inevitable event in glycosidation of sialic acid, but no such a formation was found in my hydroxymethyl derivative and the desired glycoside was obtained in high yield.
|
