EXPLORATION OF HIGH-PRESSURE CYCLOADDUCTS OF FURANS AND CITRACONIC ANHYDRIDE AS PRECURSORS FOR CD-RING FRAGMENTS OF PACLITAXEL AND ITS ANALOGS

The high-pressure promoted Diels-Alder reactions between several furan s and citraconic anhydride have been studied and the cycloadducts obta ined have been explored in new straightforward routes to the CD-ring f ragment of paclitaxel. The reaction between furan and citraconic anhyd ride afforded the exo cycloadduct diastereoselectively, whereas a vari ety of 2-substituted furans afforded approximate 1:1 mixtures of exo r egioisomers. Separation of both regioisomers was accomplished after ei ther diastereoselective esterification or regioselective reduction of the anhydride function. Ether cleavage of the bicyclic compounds by ei ther high-pressure promoted ether cleavage or Boord elimination afford ed several potential CD-ring precursors which can be used in the total synthesis of paclitaxel analogues.