1996 Fiscal Year Final Research Report Summary
Design of Glycosidation Reactions Directed toward Efficient Synthesis of Biologically Active Oligosaccharide Chains
| Project/Area Number |
07457517
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | HOKKAIDO UNIVERSITY |
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Principal Investigator |
HASHIMOTO Shunichi Hokkaido Univ., Fac.of Pharm.Sci., Professor, 薬学部, 教授 (80107391)
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| Co-Investigator(Kenkyū-buntansha) |
KITAGAKI Shinji Fac.of Pharm.Sci., Hokkaido Univ., Research Associate, 薬学部, 教務職員 (20281818)
NAKAMURA Seiichi Fac.of Pharm.Sci., Hokkaido Univ., Instructor, 薬学部, 助手 (90261320)
WATANABE Nobuhide Fac.of Pharm.Sci., Hokkaido Univ., Instructor, 薬学部, 助手 (80220911)
NAKAJIMA Makoto Fac.of Pharm.Sci., Hokkaido Univ., Lecturer, 薬学部, 講師 (50207792)
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| Project Period (FY) |
1995 – 1996
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| Keywords | Oligosaccharide Chain / Phosphorus / Leaving Group / Protection / Reactivity / Diethyl Phosphite / Stereoselectivity / Glycosidation |
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| Research Abstract |
The rapidly growing significance of oligosaccharide chains as constituents of biologically important compounds such as antitumor antibiotics, glycolipids, and glycoproteins has sparked considerable interest in the rational design and development of stereocontrolled glycosidation reactions directed toward the block synthesis.
As part of a program to develop novel and efficient glycosidation methods capitalizing on the phosphorus-containing leaving groups, we have now found that glycosyl donors incorporating diethyl phosphite exhibit not only excellent shelf-stabilities but also the following distinct advantages in the glycosidation reactions. (1) Coupling of benzyl-protected glycopyranosyl diethyl phosphites with a variety of acceptor alcohols can be effected by the aid of BF_3・OEt_2 as a promoter even at -78ﾟC to exhibit the highest 1,2-trans-beta-selectivity known to date for glycosidations with a non-participating group on O-2. (2) TMSOTf-mediated glycosidation of glycosyl phosphites bearing participating groups at C-2 constitutes an extremely mild and general method for the stereocontrolled construction of 1,2-trans-beta-glycosidic linkages. (3) A direct method for the construction of 2-deoxy-beta-glycosidic linkages has also been developed by using 2-deoxyglycopyranosyl diethyl phosphites in the presence of a catalytic amount of TMSOTf, wherein glycosidations of 2-deoxy-D-gluco-and 2-deoxy-L-rhamnopyranosyl donors with primary alcohols have been found to exhibit the highest beta-selectivity known to date.
The phosphoroamidates, which have proven to be compatible with a variety of protective group interchange conditions, play a pivotal role as the "disarmed" donors in the block synthesis of oligosaccharides based on the "armed/disarmed" concept, while the diphenylphosphinimidates, phosphorodiamidimidothioates, and diethyl phosphites can serve as the "armed" donors.
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Research Products
(12 results)
