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

Abstract: Various intramolecular [4 + 21 cycloaddition strategies directed toward the eventual total synthesis of the potent anti tumor agent paclitaxel (Taxolm) 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 diene-dienophile combination from which the desired tricyclic nucleus may be constructed by Lewis acid catalyzed cycloaddition