Synthesis and conformational studies of unnatural pyrimidine nucleosides

Starting from 3,4-di-O-acetyl-L-rhamnal (6) and thymine (7) the unsaturated nucleosides 1-(2',3',6'-trideoxy-4'-O-acetyl-alpha- and beta -L-erythro-he x-2'-enopyranosyl)thymine (8a and 8b) were prepared in anomerically pure fo rm. In solution 8a was shown to be present in the H-5(o), and H-0(5) confor mations, whereas the predominant conformation of 8b was H-5(o). Chemical tr ansformation of 8a and 8b led to the saturated nucleosides 1-(2',3',6'-trid eoxy-alpha- and beta -L-erythro-hexopyranosyl)thymine (10a and 10b, respect ively), which were converted into 1-(4'-azido-2',3',4',6'-tetradeoxy-alpha- and beta -L-threohexopyranosyl)thymine (12a and 12b). Preliminary biologic al studies showed that 9b was inactive against the HIV-1 and HIV-2 viruses.