SYNTHESES OF PACLITAXEL, ANALOGS AND INTERMEDIATES WITH VARIABLE A-RING SIDE CHAINS

摘要

An efficient protocol for the synthesis of paclitaxel, paclitaxel analogs andtheir intermediates is described. The process includes the attachment of thepaclitaxel A-ring side chain to baccatin III and for the synthesis ofpaclitaxel andpaclitaxel analogs with variable A-ring side chain structures. A rapid andhighlyefficient esterification of O-protected isoserine and 3-phenylisoserine acidshaving N-benzyloxycarbonyl groups to the C-13 hydroxyl of 7-O-protectedbaccatin III is followed by a deprotection-acylation sequence to makepaclitaxel,cephalomannine and various analogs, including photoaffinity labelingcandidates.The chemical process of the present invention for the production ofpaclitaxel,paclitaxel analogs and their intermediates may be generalized, then, as thecondensation of a compound of the general formula:(see formula I)with a taxane of the general structure:(see formula II)to give an intermediate of the general structure:(see formula III)