1997 Fiscal Year Final Research Report Summary
Stereoselective Glycosylation via Decarboxylation of Mixed Carbonate
| Project/Area Number |
08672446
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Chemical pharmacy
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| Research Institution | Teikyo University |
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Principal Investigator |
OHTAKE Hiro Teikyo University Faculty of Pharmaceutical Sciences Research Associate, 薬学部, 助手 (50256054)
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| Co-Investigator(Kenkyū-buntansha) |
AZUMAYA Isao Teikyo University Faculty of Pharmaceutical Sciences Research Associate, 薬学部, 助手 (50276755)
TAKAHASHI Hideyo Teikyo University Faculty of Pharmaceutical Sciences Research Associate, 薬学部, 助手 (10266348)
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| Project Period (FY) |
1996 – 1997
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| Keywords | Glycosylation / Decarboxylation / Carbonates / Benzyl protected sugars / Acyl protected sugars / Hafnocene dichloride / Silyl triflate / Tin (IV) chloride |
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| Research Abstract |
While study of the interglycosidic bond formation has been rapidly expanded, high-yielding and stereoselective glycosylation methods have been developed thus far. These glycosidic bond formations are generally based on the activation of glycosyl donors with leaving groups by appropriate promoters, but a different type of glycosylation is an engaging alternative, which can furnish flexible strategies for oligosaccharide synthesis. Along this line, we developed a decarboxylative glycosylation method which involves 1) linking two sugar moieties using carbonate as a connector and 2) removing internal carbon dioxide by the aid of Lewis acid to form glycosidic bond.
First, we searched suitable activating (leaving) groups for the synthesis of glycosyl carbonates. Using 4-nitrophenyl carbonates as active carbonates, the mixed carbonates of benzyl protected sugars were prepared in good yields. The imidazolides could be also used when a tedious chromatographic separation was needed to remove a by-product (bis (4-nitrophenyl) carbonate). In the case of acyl sugars, succinimidyl carbonates generally gave the best yield and beta-selectivity at the anomeric position, which effected beta-selectivity in the next glycosylation.
In surveying promoters, various Lewis acids were found to cause decarboxylative glycosylation. An equimoler amount of TMSOTf promoted the decarboxylation of benzyl protected glycosyl carbonates in toluene to form glycosides beta-preferentially (-1 : 4). The reaction proceeded by a catalytic amount of TMSOTf, though the lower selectivity was observed because of the longer reaction time. The combination of SnCl_4-AgClO_4 or Cp_2HfCl_2-2AgClO_4 catalytically promoted the decarboxylation in ether to give glycosides alpha-selectively (8 : 1-19 : 1). Acyl protected mixed carbonates obtained as beta-anomer were promoted by an equimoler amount of TMSOTf in dichloromethane to give the corresponding pure beta-glycoside in high yield.
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