Studies on the total synthesis of putative intermediates in the biosynthesis of taxol

Abstract

The exploration of several strategies for the synthesis of taxoids useful for studying the biosynthesis of taxol is presented. The approaches described include attempts to access the taxane carbon skeleton through closure of the B-ring across the C-2 – C-3 bond or the C-10 – C-11 bond, as well as attempts to form the A- and B-rings using an intramolecular Diels-Alder reaction. Attempts to close the C-2 – C-3 bond employed an ally! silane to attack either a ketone, aldehyde, or acetal to close the B-ring in an intramolecular Sakurai reaction. The preparation of four substrates suited to undergo this type of ring closure is described. Attempts to close the B-ring across the C-10 – C-11 bond focused on converting a vinyl halide to the corresponding vinyl chromium or vinyl palladium and closing the Bring through either a Nozaki-Hiyama-Kishi reaction or a Heck reaction. The preparation of six substrates suited to undergo ring closure through this means is described. Attempts to form the A- and B-rings using an intramolecular Diels-Alder reaction were made. The preparation of three substrates suited to undergo ring closure through this means is described.