Stereospecific synthesis of phosphotriesters by using new condensing reagents

• 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
• Project Status: Completed (Fiscal Year 1986)
• Budget Amount: ¥1,900,000 (Direct Cost: ¥1,900,000); Fiscal Year 1986: ¥200,000 (Direct Cost: ¥200,000); Fiscal Year 1985: ¥200,000 (Direct Cost: ¥200,000); Fiscal Year 1984: ¥1,500,000 (Direct Cost: ¥1,500,000)
• 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.

Research Products

• [Publications] Eiko Ohtsuka, Zenzaburo Tozuka and Morio Ikehara: "New condensing reagents for stereospecific synthesis of dinucleoside monophosphate aryl esters" Tetrahedron Letters. 22 (45). 4483-4486 (1981)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Eiko Ohtsuka, Zenzaburo Tozuka, Shigenori Iwai and Morio Ikehara: "A new condensing reagent, 1-(2,4,6-triisopropylbenzenesulfonyl)-5-(pyridin-2-yl) tetrazolide and its use in the synthesis of cro binding heptadecanucleotide on a polymer support" Nucleic Acids Research. 10 (20). 6235-6241 (1982)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Eiko Ohtsuka, Masahiko Shiraishi and Morio Ikehara: "Stereospecific synthesis of dinucleoside monophosphate aryl esters by using new condensing reagents" Phosphorus and Sulfer. 18. 365-368 (1983)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Eiko Ohtsuka, Masahiko Shiraishi and Morio Ikehara: "Stereoselective synthesis of dinucleoside phosphate aryl esters by using new condensing reagents, arenesulfonyl 5-(pyridin-2-yl)-tetrazole" Tetrahedron. 41 (22). 5271-5277 (1985)
  • Description: 「研究成果報告書概要(欧文)」より