1986 Fiscal Year Final Research Report Summary

Stereospecific synthesis of phosphotriesters by using new condensing reagents

Research Project

Project/Area Number	59570894
Research Category	Grant-in-Aid for General Scientific Research (C)
Allocation Type	Single-year Grants
Research Field	Chemical pharmacy
Research Institution	Hokkaido University (1985-1986) Osaka University (1984)
Principal Investigator	OHTSUKA Eiko Hokkaido University Fac.of Pharmaceutical Sciences, Prof, 薬学部, 教授 (80028836)
Project Period (FY)	1984 – 1986
Keywords	Phosphotriester method / condensing reagent / Oligonucleotide / シアステレオマー
Research Abstract	Deoxyadenylyl-(3'-5')-phosphoro-o-chlorophenyl deoxyadenosine having the Sp configuration was synthesized stereoselectively by condensing N,5'-bis-dimethoxytrityldeoxyadenosine 3'-(o-chlorophenyl)phosphate with N,3'-bis-dimethoxytrityldeoxyadenosine using 1-2,4,6-triisopropylbenzene-5-(pyridin-2-yl)tetrazole as the condensing reagent followed by dedimethoxytritylation. The absolute configuration of this diastereomer was determined spectroscopically by comparison of two corresponding diastereomers which were prepared by using a conventional condensing reagent and isolated by chromatography on silica gel. Their nuclear Overhauser effect in proton magnetic resonances and the circular dichroism of these two diastereoisomers could only be explained if the product obtained by the stereoselective synthesis of this type exist in solution as an equilibrium of folded and extended forms.