Stereoselective Synthesis of 2'-Amino-2',3'-dideoxynucleosides by Nitrone 1,3-Dipolar Cycloaddition: A New Efficient Entry Toward d4T and Its 2-Methyl Analogue

Ugo Chiacchio; Antonio Rescifina; Daniela Iannazzo; Giovanni Romeo

doi:10.1021/jo972264i

Stereoselective Synthesis of 2'-Amino-2',3'-dideoxynucleosides by Nitrone 1,3-Dipolar Cycloaddition: A New Efficient Entry Toward d4T and Its 2-Methyl Analogue

J Org Chem. 1999 Jan 8;64(1):28-36. doi: 10.1021/jo972264i.

Authors

Ugo Chiacchio¹, Antonio Rescifina, Daniela Iannazzo, Giovanni Romeo

Affiliation

¹ Dipartimento di Scienze Chimiche, Viale A. Doria 6, Università di Catania, Italy, and Dipartimento Farmaco-Chimico, Viale SS. Annunziata, Università di Messina, Italy.

PMID: 11674081
DOI: 10.1021/jo972264i

Abstract

An efficient access to 2'-(dimethylamino)-2',3'-dideoxynucleosides is reported. The synthetic strategy relies on the 1,3-dipolar cycloaddition of C-alkoxycarbonyl nitrones to allyl acetate, followed by reductive ring opening to substituted lactones, DIBALH reduction to the corresponding 3-(dimethylamino)tetrahydro-2-furanols, and coupling with silylated thymine. The removal of the dimethylamino group by Cope elimination affords a new formal synthesis of d4T and analogous unsaturated 2',3'-dideoxynucleosides.