Synthesis of carbocyclic nucleosides: synthesis of (±)-2,2-bis(hydroxymethyl)cyclopropyl nucleosides

Abstract

Treatment of 2,2-bis(benzyloxymethyl)cyclopropanecarboxylic acid 8 with ethyl chloroformate and sodium azide followed by thermolysis of the resulting keto azide 9 at 80 °C provided the corresponding isocyanate 10, which was then converted into 2,2-bis(benzyloxymethyl)cyclopropylurea 11 and 2,2-bis(benzyloxymethyl)cyclopropylamine 13. The racemic 2,2-bis(hydroxymethyl)cyclopropylpyrimidine nucleosides 16, 21, 22, 23, 26, 29, and 31 and the purine nucleosides 39 and 41 were prepared from compounds 11 and 13, respectively; they showed no antiviral activity against HSV-1, HSV-2, HCMV, and HIV-1 in cell culture.