From tartrate to taxoids: A double, intramolecular Diels-Alder strategy

Abstract

Various intramolecular [4 + 2] cycloaddition strategies directed toward the eventual total synthesis of the potent anti tumor agent paclitaxel (Taxol®) are outlined. The initial model studies employed a substituted cyclohexene to hold the dienophile and the diene in proximity for the cycloaddition to yield the requisite tricyclo[9.3.1.03,8]pentadecene skeleton. Routes to ring A building blocks and the appropriate dienes have been developed and elaborated into more highly substituted Diels-Alder precursors. Unfortunately, these failed to cyclize and a new strategy has been selected in which a tartrate "tether control group" both directed the initial cycloaddition to a substituted decalin and imparted the required asymmetry. Ring cleavage followed by selective functional group manipulation will afford a new dienedienophile combination from which the desired tricyclic nucleus may be constructed by Lewis acid catalyzed cycloaddition.