A Short Synthesis of a Novel Ring-Expanded Purine and Its Nucleoside Analogue Containing the Imidazo[4,5-<i>e</i>][1,3]diazepine Ring Skeleton with Multiple Amino Substituents Attached to the 7-Membered Ring

Abstract

Abstract The synthesis of 4,6,8-triaminoimidazo[4,5-e][1,3]diazepine (1) and its nacleoside analogue (6) are reported. The heterocycle was prepared in a single step by condensation of 4,5-dicyanoimidazole with guanidine. The 5,7-fused ring structure of 1 was distinguished from the other possible 5:5-fused isomer 2 by preparing the 15N-labeled heterocycle (1∗) and exploring its 15N-1H coupling patterns in both 1H and 15N NMR spectra. These spectral patterns also enabled establishment of the triamino tautomeric form of 1 as assigned. Compound 1, a novel ring-expanded (“fat”) analogue of purine, is anticipated to be planar and aromatic as predicted by molecular modeling. The 1 -benzyl analogue (4), a protocol for the ribosyl analogue 6, was similarly prepared from 1-benzyl-4,5-dicyanoimidazole. The nucleoside 6 was prepared by the modified Vorbrülggen ribosylation of 1. The position of ribosylation was unequivocally established by an unambiguous synthesis of 6 from condensation of 1 -(2′,3′,5-tri-O-benzoyl-β-D-ribofuranosyl)-4,5-dicyanoimidazole (7) with guanidine in a solution of sodium methoxide in methanol. The nucleoside 7 was prepared by the Vorbrüggen ribosylation of 4,5-dicyanoimidazole.