合成路线1

A total synthesis of paclitaxel has been reported: 1) The starting material is the previously known bicyclic diol ester (I), which is silylated with tert-butyldimethylsilyl trifluoromethylsulfonyl (TBSTf) and reduced with LiAlH4 in ether at 0 C to give the hydroxy lactone (II). The reaction of (II) with camphorsulfonic acid (CSA) and then with tert-butyldiphenylsilyl chloride (TPSCl) followed by a treatment with benzyl bromide and KH in ether yields the fully protected lactone (III), which is reductively opened with LiAlH4 in ether at 25 C (a simultaneous partial desilylation takes place), affording the triol (IV). The reaction of (IV) with 2,2-dimethoxypropane and CSA gives the acetonide (V), which is oxidized with tetrapropylammonium perruthenate (TPAP) to the aldehyde (VI). The condensation of (VI) with the previously known sulfonyl hydrazone (VII) by means of BuLi in THF gives the methanol derivative (VIII), which is epoxidized with VO(AcAc)2 and tert-butyl hydroperoxide in benzene, yielding the epoxide (IX). Opening of the epoxide (IX) with LiAlH4 in ether affords the 1,2-diol (X), which is treated with phosgene and KH to give the cyclic carbonate (XI). The desilylation of (XI) with tetrabutylammonium fluoride (TBAF) followed by oxidation with TPAP in acetonitrile/dichloromethane yields the dialdehyde (XII), which is cyclized by means of TiCl3 and Zn-Cu, affording the racemic vicinal diol (XIII); the suitable active enantiomer is obtained by optical resolution with 1(S)-(-)-camphanic acid chloride. Selective acetylation of (XIII) with acetic anhydride and dimethylaminopyridine (DMAP) followed by oxidation with TPAP and N-methylmorpholine N-oxide (NMO) gives the acetoxy ketone (XIV). The hydroboration of (XIV) with BH3 followed by oxidation with H2O2 and hydrolysis of the acetonide group with HCl yields the trihydroxy compound (XV).