Determination of the (2E,4E)-Geometryof the 3,5-Dimethyl-2,4-diene System of Antibiotic 1233A by NMR Comparison with the Four Geometrical Isomers of Methyl 3,5-Dimethyl-2,4-heptadienoate

Abstract

(2E,4E)-geometry was assigned to 1233A [(7R,2ʹR,3ʹR)-11-[3ʹ-(hydroxymethyl)-4ʹ-oxo-2ʹ-oxetanoyl]-3,5,7-trimethyl-2,4-undecadienoic acid (1a)], an inhibitor of cholesterol biosynthesis. Both the 1H- and 13C-NMR spectra of 1a and methyl ester 1b were compared with those of the four geometrical isomers of methyl 3,5-dimethyl-2,4-heptadienoate (2). NOE experiments on 1b revealed the presence of a remarkable NOE between the proton at C-2 and those of the C-17 methyl group. Similar NOE was also observed with (2E,4E)-2. This fact suggests the predominant existence of stable s-cis-rotamers at the single bond between C-3 and C-4 of 1b and of (2E,4E)-2. Some MM2 calculations were attempted to show the presence of two types of stable conformers in the case of the 3,5-dimethyl-2,4-dienoate system.