1998 Fiscal Year Final Research Report Summary
Studies on Design and Synthesis of Glycoconjugate Drugs with Targeting
| Project/Area Number |
08557119
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Chemical pharmacy
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
HASHIMOTO Shun-ichi Graduate School of Pharm.Sci., Hokkaido University, Professor, 大学院・薬学研究科, 教授 (80107391)
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| Co-Investigator(Kenkyū-buntansha) |
KITAGAKI Shinji Graduate School of Pharm.Sci., Hokkaido University, Instructor, 大学院・薬学研究科, 助手 (20281818)
NAKAMURA Seiichi Graduate School of Pharm.Sci., Hokkaido University, Instructor, 大学院・薬学研究科, 助手 (90261320)
NAKAJIMA Makoto Graduate School of Pharm.Sci., Hokkaido University, Asso.Professor, 大学院・薬学研究科, 助教授 (50207792)
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| Project Period (FY) |
1996 – 1998
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| Keywords | Glycosidation / Phosphorus / Leaving Group / Sugar / Drug / Antibiotics / Stereoselectivity / Targeting |
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| Research Abstract |
Due to the rapidly recognized biological significance of saccharide residues of carbohydrate-containing biomolecules, the rational design and development of stereocontrolled glycosidation reactions are of growing importance not only in carbohydrate chemistry but also in medicinal chemistry.
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
… More
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 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. (4) A direct glycosidation for the stereocontrolled construction of 1 , 2-cis-beta-mannnosides, a long-standing and formidable problem, has been achieved by exploiting 4,6-O-benzylidene-protected mannopyranosyl diethyl phosphites in the presence ofTMSOTf, though the method is limited to primary alcohols. (5) A highly stereocontrolled 1,2-cis-alpha-glycosidation under conditions mild enough for acid-labile alcohols has been developed by using benzyl-protected glycopyranosyl diethyl phosphites as glycosyl donors in the presence of 2,6-di-tert-butylpyridinium iodide and tetrabutylammonium iodide. Less
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