1998 Fiscal Year Final Research Report Summary
synthesis of biologically active compounds for the conrol of signal transduction by using phosphorus functional group
| Project/Area Number |
09672162
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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 | Tokyo University of Pharmacy and Life Science |
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Principal Investigator |
SHIBUYA Shiroshi Tokyo Univ.Pharm.& Life Science School of Pharmacy, Professor, 薬学部, 教授 (10057325)
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| Project Period (FY) |
1997 – 1998
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| Keywords | stereoselective synthesis / asymmetric dihydroxylation / phosphotyrosine / lipase / purine nucleoside phosphorylase / 2-dexyribose 3-phosphonate / glycosylation / radical cyclization |
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| Research Abstract |
Biologically active compounds for the conrol of signal transduction were synthesized by an application of phosphorus functional group.
1. Asymmetric dihydroxylation of 1(E)-alkenylphosphonates afforded the corresponding threo-alpha, beta-dihydroxyphosphonates. Good enantioselectivty was obadserved in the AD reaction of 1(E)-alkenylphosphonates with conjugated aromatic substituents. In the asymmetric dihydroxylation of racemic mixture of 1-acyloxy-2(E)-alkenylphosphonates with AD-mix-alpha- or beta-reagents, the kinetic rate of dihydroxylation was highly dependent upon the configuration of the 1-acyloxy functional group as well as the nature of the substitutent at the 3-position.
2. (Phosphonomethyl)phenylalanine and (phosphonodifluoromethyl)phenylalanine and their beta-amino acid congeneres, stable analogues of phosphotyrosine, were prepared from 2-benzyl-1, 3-propanediols possessing either a dithylphosphonomethyl- or diethylphosphonodifluoromethyl functionality at the para position via the lipase-catalyzed desymmetrization.
3. Methylene phosphonate analogues of thymidine 3'-phosphate and 2'-deoxyuridine 3'-phosphate were prepared in a stereocontrolled manner through intramolecular N-glycosilation of phenyl 2,3-dideoxy-3-diethylphosphonomethyl-5-O-(2-pyrimydinyl)- 1 -thioglycosides, followed by acid hydrolysis. N-glycolylation of 3-(diethoxyphosorothioyl)methyl-5-O-benzoyl-O-ethyl-2,3 -dideoxy-riboses with silylated thymidine in the presence of TiCI_4 proceeded highly diastereoselectivly to give the corresponding beta-nucleotide analogues in good yield. A remarkable neighboring group participation of the methylenephosphonothioate functionality was obaserved in the course of the beta-N-glycosylation.
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Research Products
(12 results)
