Carbocyclic 4-Deazaformycins

Abstract

The preparation of carbocyclic 4-deazaformycin and its 5′-homoanalogue from a common vinyl precursor, and its N-1 and N-2 methyl derivatives is reported. The syntheses began with a highly stereoselective SN2 reaction between lithio 4-picolines and a protected 2,3-dihydroxy-4-vinylcyclopentyl triflate. The requisite fused pyrazole ring was created by an intramolecular diazonium reaction that was followed by vinyl transformation into the hydroxymethyl and the hydroxyethyl groups. The N-methyl derivatives arose by standard methylation conditions and the resultant N-Me regiochemistry was assigned by homo- and heteronuclear NMR spectroscopy.