An alternative method for the synthesis of 2′-halogeno-1′,2′-unsaturated uridine derivatives through syn-elimination of pivalic acid of 2′-halogeno- 2′-deoxy-1′-pivaloyloxyuracil nucleoside: preparation of its 2′-C-branched nucleosides

Abstract

An alternative method for the preparation of 2′-bromo- (5b) and 2′-iodo- (5c) 1′,2′-unsaturated uracil nucleosides has been developed. The protocol was on the basis of the syn-elimination of pivalic acid from 2′-bromo-(7a,b) and 2′-iodo-(9a,b) 1′-pivaloyloxy-2′-deoxyuridine derivatives, which were derived from the halo-pivaloyloxylation of 3′,5′-bis-O-TBDMS-1′,2′-unsaturated uridine 1. Compounds 5b and 5c were shown to serve as versatile synthons for the respective 2′-C-branched 1′,2′-unsaturated uracil nucleosides, through palladium-catalyzed cross-coupling or halogen-lithium exchange reactions.

Graphical Abstract

Keywords:

• Nucleoside
• unsaturated sugar
• electrophilic addition
• syn-elimination
• Pd-catalyst
• cross-coupling
• halogen–lithium exchange reaction

Additional information

Funding

Financial supports from Japan Society for the Promotion of Science (KAKENHI No. 24590144 to K. H.) are gratefully acknowledged.