Synthesis of 2 '- and 3 '-amino-substituted uridine, thymidine and adenosine, and their inhibitions of HIV replication

Reactions of primary and secondary amines with appropriately protected 2'-O-mesyl-3'-deoxynucleosides 1, 5, and 18 gave 2',3'-dideoxy-2'-alkylaminonucleosides 2a-d, 6a-c and 19a-d, f, n-q (35-40%) as well as a small amount of 2',3'-glyceropentofuranosyl nucleoside 3, 7 or 11 (similar to 15%). Displacement of the 3'-O-mesyl group in 9b with amines gave mainly the elimination product 11, except in the reaction with morpholine and benzylamine which gave 3'-aminosubstituted products 10c and 10d at a yield of 52% and 24%, respectively. The ring-opening reactions of appropriately protected 2', 3',-0-lyxoanhydro-adenosine 13 by a variety of primary and secondary amines gave isomeric mixtures of 2'-alkylamino nucleosides 15a-k (similar to 20%) and 3'-alkylamino nucleosides 14a-m (similar to 60%). These alkylamino nucleosides have been subsequently deprotected under acidic conditions to give the parent nucleosides in good yields; their biological activities as inhibitors of human immunodeficiency virus (H IV) replication have been also evaluated. The 2',3'-dideoxy-2'-substituted and 2',3'dideoxy-3'-substituted nucleosides described herein are not available through any other known routes.