Introduction of substituents to the 7(8)-position of 7-deazaadenosine (tubercidin): conversion to toyocamycin.

ABSTRACT

Treatment of 2',3',5'-tri-O-acetyl-7-deazaadenosine with C1SCN gave the 7-thiocyanato derivative, which was converted to 7-methylthio and 7-methyl-sulfone derivatives. The thio-Claisen rearrangement and desulfurization of 7-allylthio derivative afforded 7-propyl-7-deazaadenosine. The 7-methylsulfone derivative gave the 8-cyano compound by treatment with NaCN. The action of nitrating agent on triacetyltubercidin gave a mixture of the 7- and 8-nitro derivatives. The Mannich reaction of tubercidin gave the 7-morpholinomethyl derivative which was converted to the methyl, formyl, hydroxymethyl, or cyano derivatives in good yield. The conversion of tubercidin to toyocamycin was thus accomplished. Some physical and biological properties of these substituted tubercidins were presented.