ACYCLIC PURINE NUCLEOSIDE ANALOGS - COMPUTATIONAL AND NMR-STUDIES OF CONFORMATIONAL BEHAVIOR

The conformational space of N-7- and N-9-(2-hydroxypropyl)-6-(N-pyrrol yl)purine as well as of N-7- and N-9-(2,3-dihydroxypropyl)-6-(N-pyrrol yl)purine has been studied by molecular mechanics (MMX force field) an d semiempirical (PM3) calculations. Eight local minima were obtained f or the N-7-(2-hydroxypropyl) regioisomer by the MMX force field and re optimised by the PM3 method to locate the global minimum. The conforma tion of the N-7-(2,3-dihydroxypropyl) regioisomer is locked by intramo lecular H-bonding and therefore more rigid. The results of theoretical calculations are in agreement with H-1 and C-13 NMR analysis of subst ituent chemical shifts, C-H and H-H coupling constants and connectivit ies in 2D homo- and heteronuclear correlation spectra. (C) 1997 Elsevi er Science B.V.