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.
ASJC Scopus subject areas
- Organic Chemistry