Assignment of the absolute configuration of large molecules by ab initio calculation of the rotatory power within a small basis set scheme: the case of some biologically active natural products

Abstract

Ab initio calculations of the optical rotatory power (ORP) of some natural products 1– 12 showing interesting biological properties (they are antibiotics, antimalarials, aromas and fragrances) have been carried out by means of the Hartree–Fock (HF) and density functional theory methods and small basis sets, using available packages such as dalton 1.2 and gaussian 03. The results obtained fully support our previous conclusion [ J. Org. Chem. 2003, 68, 5186] that for aromatic and/or largely unsaturated molecules, if the [ α] D is determined in sign and order of magnitude by the lowest-energy Cotton effect(s), the result of such simplified ab initio calculations of the ORP is completely reliable. When possible (i.e., small size molecules) the prediction made using extended (with diffuse functions) basis sets affords practically similar values. Therefore, even large molecules (50–60 atoms) can be treated using common desktop computers: this result is very important from a practical point of view. Compounds 8 and 12 did not fulfil the above criterion and therefore require a more accurate treatment.