31P NMR Study of the Mechanism of Activation and Coupling Reactions in the Synthesis of Oligodeoxyribonucleotides by the Phosphotriester Method

Srinivasan Chandrasegaran, Akira Murakami, Lou Sing Kan

Research output: Contribution to journalArticle

Abstract

The phosphotriester method provides a rapid and convenient procedure for synthesizing oligonucleotides. The mechanism has been revealed and intermediates have been identified by 31P NMR methodology. It was found that reaction of a 5'-protected nucleoside 3'-(p-chlorophenyl phosphate) with mesitylenesulfonyl chloride (MSC1) or 1-(mesitylyl-2-sulfonyl)-3-nitro-1,2,4-triazole (MSNT) in anhydrous pyridine yields only two products within 5 min, the sulfonic acid-phosphate mixed anhydride 2 and the (3'-3') symmetrical pyrophosphate tetraester 3 which can be isolated as a mixture. Reaction of 2 and 3 with 3'-O-acetylthymidine yields the phosphotriester dimer [(MeO)2Tr]NpTOAc. The reaction rate and yield of dimers are closely dependent on the presence of catalysts. The reaction finished within minutes when tetrazole or 3-nitro-1,2,4-triazole was used. On the contrary, the reaction completed in hours when imidazole or 1,2,4-triazole was used as catalysts. The possible mechanisms are explored and discussed in detail.

Original languageEnglish (US)
Pages (from-to)4951-4957
Number of pages7
JournalJournal of Organic Chemistry
Volume49
Issue number25
DOIs
StatePublished - Jun 1984

ASJC Scopus subject areas

  • Organic Chemistry

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