Synthetic routes to nucieoside analogs of N-substituted 1-oxa-4-azacyclohexanes and 1-thia-4-azacyclohexanes. 13C nuclear magnetic resonance spectra of six-membered, cyclic amides

Abstract

Nucleoside analogs, namely 6-chloro-9-(4-benzoyl-1-oxa-4-azacyclohexan-2-yl)-9H-purine 6 and 6-chloro-9-(4-benzoyl-1-thia-4-azacyclohexan-2-yl)-9H-purine 7, were obtained by treatment of 4-benzoyl-2-hydroxy-1-oxa-4-azacyclohexane 13 and 4-benzoyl-2-hydroxy-1-thia-4-azacyclohexane18, respectively, with 6-chloropurine, methyldiphenylphosphine, and diethyl azodicarboxylate in refluxing tetrahydrofuran. Compounds 13 and 18 were obtained by O-deacetylation of the corresponding 2-acetoxy derivatives 11 and 16 with a catalytic amount of sodium methoxide in chloroform. 2-Acetoxy-4-benzoyl-1-oxa-4-azacyclohexane 11 was obtained from 4-benzoyl-1-oxa-4-azacyclohexane 10 by treatment with tert-butyl peracetate, cuprous chloride, and benzene, whereas 2-acetoxy-4-benzoyl-1-thia-4-azacyclohexane 16 was prepared by a Pummerer reaction with 4-benzoyl-1-thia-4-azacyclohexane 1-oxide 15. The13C nmr spectra of all the compounds are reported; the spectra provided unambiguous proof of structure.