Assignment of the absolute configuration of (-)-linarinic acid by theoretical calculation and asymmetric total synthesis

Abstract

The specific rotation of (-)-linarinic acid calculated using Hartree-Fock and density functional theory on 14 representative conformers of this molecule were all negative. The most stable conformer was found to be almost identical to the crystallographic structure. These results are consistent with the assumption that (-)-linarinic acid has a (1S)-configuration. An asymmetric total synthesis with starting products chosen on the basis of the theoretical calculations was found to corroborate the theoretical assignment. On the basis of the theoretical calculations of specific rotations and a total asymmetric synthesis, the absolute configuration of the natural product (-)-linarinic acid was determined to be 1S. © 2005 Elsevier Ltd. All rights reserved.