Peptide analogs containing the pentacyclo[5,4,0,02,6,03,6,05,9]undecane scaffold: conformational analysis in solution

In order to evaluate the conformational preferences of depsipeptides attached to polycyclic compounds, we have investigated conformational preferences in solution by NMR spectroscopy and in the theoretical domain by dynamic simulation, semi-empirical and ab initio calculations. In CDCl3 solution, the polycyclic scaffolds 8 and 10 displayed different types of turn conformation while compounds 9, 11, (^)-12 and (^)-13 displayed a well-defined turn structure, characterized, respectively, by a eight-membered hydrogen-bonded ring and by a g-like strand hydrogen-bonded ring for each peptide chain. In a strong solvating medium such as DMSO-d6 the depsipeptide (^)-12 adopts a g-like strand hydrogen-bonded ring for one peptide chain and, for the other one, a bifurcated H-bond formed by a g-like strand and a non-classical C5-structure. Theoretical calculations, supported by the experimental data, made it possible to identify these conformations and were of great importance in the discussion of the observed results. q 2003 Elsevier B.V. All rights reserved.