Design and synthetic approach to a taxoid analogue.

Abstract

The design and synthetic strategy towards a taxoid analogue that contains the important functional groups required for biological activity is described. The key reactions include a directed ortho metalation and a tether controlled intramolecular Diels-Alder reaction. Commercially available 4-bromobenzyl bromide (20) was successfully converted to the benzamide (39) via a metal-halogen exchange reaction, followed by a directed ortho metalation reaction. Addition of iododiene (13) to the benzamide provided amide 59. This amide was then lactonized to 61 in quantitative yield. Reduction of the lactone has yielded the diol in good yield. Oxidation of the selectively protected diol would give aldehyde 93, which after Grignard addition will produce the Diels-Alder precursor 94.