Studies towards the total synthesis of 1-deoxy-8-demethyl taxol.

摘要

The total synthesis towards 1-deoxytaxol analogs is described. The synthesis relies on new methods to install the C3-C4 bond and to achieve the tricyclic taxane ring skeleton.;The first section describes the formation of the C3-C4 bond via a highly stereoselective one pot tandem enone formation and Michael addition reaction. The precursor for the tandem reaction was prepared from a taxane AB-ring intermediate which was developed for the synthesis of 1-deoxytaxol analogs in our laboratory. An elimination reaction provided a transient alpha,beta-unsaturated ketone and the following intramolecular Michael addition reaction produced the desired C3-C4 bond-linked lactone as a single diastereomer.;Section two describes the highly efficient C-ring closure by consecutive Michael addition and aldol condensation reaction of the previously obtained lactone. Indeed, Michael addition with acrolein led to the corresponding aldehyde adduct. The aldehyde was then employed for the intramolecular aldol condensation reaction to give the crucial tricyclic taxane intermediate.;In the third section, preliminary studies describing the reactivity of the taxane intermediate towards the synthesis of 1,7-dideoxy-8-demethyltaxol are reported.