A simple method for the assignment of the relative stereochemistry of 2-substituted clavams

Abstract

Bentley and Hunt’s empirical rule for the determination of the anti/syn relationship of protons attached to C-2 and C-5 atoms in 2-substituted clavams does not predict the correct stereochemistry in a series of 2-substituted clavams synthesised by us. In this paper we propose a simple method for determination of the relative stereochemistry of 2-substituted clavams based on nuclear Overhauser effect (NOE) experiments and assignment of the diastereotopicity of protons attached to the C-3 atom. Circular dichroism (CD) measurements and X-ray crystallography provide stereochemical and spectral assignments.