Synthesis of 1- and 1,2,2′-Deuteriated Deoxyribose and Incorporation into Deoxyribonucleosides

Richard P. Hodge, Charles K. Brush, Constance M. Harris, Thomas M. Harris

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Abstract

Thymidine, deoxycytidine, deoxyadenosine, and deoxyguanosine have been prepared with deuterium substitution at position 1′ and at positions 1′, 2′, and 2″ from deuteriated deoxyribose. The synthetic strategy involved reduction of the bis(tert-butyldimethylsilyl) derivative 4a of 2-deoxyribonolactone (3a) with Dibal-D followed by deprotection (HCl/MeOH and tetrabutylammonium fluoride) to give 1-deuterio methyl glycoside 7a which was converted to the 1-deuterio 3,5-ditoluoyl methyl glycoside 8a. Preliminary exchange of 2-deoxyribonolactone with NaOMe/MeOD brought about 2,2′-dideuteriation; treatment as above gave the 1,2,2′-trideuterio 3,5-ditoluoyl methyl glycoside 8b. 8a and 8b were condensed with heterocyclic bases via α-chloro derivatives 9a and 9b to form deoxynucleosides. New methods were utilized for preparation of deoxycytidine and deoxyguanosine which are improvements over published procedures.

Original languageEnglish (US)
Pages (from-to)1553-1564
Number of pages12
JournalJournal of Organic Chemistry
Volume56
Issue number4
DOIs
StatePublished - Feb 1 1991

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ASJC Scopus subject areas

  • Organic Chemistry

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