ANOMERIC EFFECT IN PURINE NUCLEOSIDES - EVALUATION OF THE STERIC EFFECT OF A PURINIC AGLYCON FROM THE PSEUDOROTATIONAL EQUILIBRIUM OF CYCLOPENTANE IN CARBOCYCLIC C-NUCLEOSIDE-1
M. Polak et al., ANOMERIC EFFECT IN PURINE NUCLEOSIDES - EVALUATION OF THE STERIC EFFECT OF A PURINIC AGLYCON FROM THE PSEUDOROTATIONAL EQUILIBRIUM OF CYCLOPENTANE IN CARBOCYCLIC C-NUCLEOSIDE-1, Journal of the American Chemical Society, 120(11), 1998, pp. 2508-2513
A variable temperature 600 MHz H-1 NMR conformational analysis of (3)J
(HH) coupling constants in pyrazolo[4,3-c]pyridine carbaribo-C-nucleos
ide 1 in D2O has shown that the carbocyclic nucleoside analogues in wh
ich the furanose ring is replaced by a cyclopentane are involved in a
two-state N reversible arrow S (north reversible arrow south) pseudoro
tational equilibrium, which is in the case of 1 strongly biased toward
an S-type conformation (P = 137 degrees, Psi(m) = 37 degrees, 90% at
298 K). The van't Hoff analysis of the population changes with tempera
ture has shown that the pseudorotational equilibrium in 1 is driven to
ward S by a Delta H degrees of -11.6 kJ mol(-1). The two-state dynamic
equilibrium is supported by ab initio calculations at HF, DFT, and MP
2 levels which showed two energy wells in the N and S regions of confo
rmational space. At the MP2/6-31(d) level the S-type conformer is pref
erred by 10.9 kJ mol(-1) over the local minimum in the N region of con
formational space, which is in excellent agreement with our experiment
al value from the conformational analysis of (3)J(HH), The N and S ene
rgy minima are separated with the energy barrier of 24.0 kJ mol(-1) at
the MP2 level, which suggests a rapid exchange on the NMR time scale
between the interconverting conformers. The experimental quantitative
estimate of Delta H(steric)degrees (-12.0 kJ mol(-1)) of the pyrazolop
yridine moiety, which has been assumed to be isosteric with the purine
moiety, has been used to calculate the energetic strengths of the O4'
-Cl'-N9 anomeric effects of adenine and guanine in N-nucleosides: 16.4
kJ mol(-1) in ddA and ddG, 14.7 kJ mol(-1) in dA, 16.4 kJ mol(-1) in
dG, 13.9 kJ mol(-1) in A, and 15.3 kJ mol(-1) in G.