Whole-Cell Biotransformation of m -Ethyltoluene into 1 S ,6 R -5-Ethyl-1,6-dihydroxycyclohexa-2,4-diene-1-carboxylic Acid as an Approach to the C-Ring of the Binary Indole�Indoline Alkaloid Vinblastine.

Abstract

The title compound 3, a potential building block for the construction of analogues of the clinically important anticancer agent vinblastine (1), has been prepared in an efficient manner through a whole-cell biotransformation of m-ethyltoluene (4) using the microorganism Pseudomonas putida BGXM1 which expresses the enzyme toluate dioxygenase (TADO). Metabolite 3 was readily converted into derivatives 5-8 using conventional chemical techniques and the structure, including absolute stereochemistry, of the last of these was established by single-crystal X-ray analysis.