Synthesis and structural study of carbocyclic analogues of 1,2-disubstituted nucleosides

Abstract

The compounds ( ± )-cis-and ( ± )-trans-9-[(2-hydroxymethyl) cyclopentyl]guanine (1 and 2 respectively) were efficiently synthesized by the construction of the purine base on the primary amino group of cis-and trans-2-aminocyclopentylmethanol. The 3D structures of these two 1,2-disubstituted carbanucleosides in DMSO were determined using molecular dynamics calculations with experimental NMR restraints on the basis of the information obtained from a ROESY spectrum. These structures were compared with those obtained in vacuo using molecular dynamics and AM1 semiempirical calculations. The global structures of the two compounds are very similar in the two environments studied, meaning that the structural determination in the gas phase can be extrapolated to molecular simulation studies in solution for compounds of this type.

Interplay of thermochemistry and Structural Chemistry, the journal (volume 17, 2006) and the discipline

“…In the next paper Martinez-Bisbal et al [259] report on the syntheses and experimental and theoretical structural analysis of (±)-cis-and (±)-trans-9-[(2-hydroxymethyl) cyclopentyl]guanine and showed that that for compounds of this type the structural determination in the gas phase can be extrapolated to molecular simulation studies in solution. The enthalpy of formation of these species and that of the related natural nucleoside, guanosine, remain unknown.…”