合成路线1

The first part of a total synthesis of paclitaxel has been published: The silylation of tricyclic diol (I) (readily available from camphor) with triethylsilyl chloride (TESCl) gives compound (II), which is submitted to epoxy alcohol fragmentation followed by silylation to yield the silylated cyclic ketone (III). The magnesium enolate of (III) is submitted to an aldol condensation with 4-pentenal (IV) to afford the ketol (V), which is protected with COCl2 and EtOH, giving the carbonate ester (VI). The hydroxylation of (VI) with lithium diisopropylamide (LDA) and (+)-camphorsulfonyl oxaziridine (VII) yields the alpha-hydroxy ketone (VIII), which is reduced with Red-Al in toluene, affording the alpha-diol (IX). The reaction of (IX) with COCl2 in pyridine gives the cyclic carbonate (X), which is oxidized with the Swern oxidant to the ketone (XI). The rearrangement of (XI) with lithium 2,2,6,6-tetramethylpiperidide (LTMP) yields the hydroxy lactone (XII), which is reduced with samarium diiodide to the stable enol (XIII), which by treatment with silica gel gives a mixture of cis- and trans-oxolactones (cis-XIV + trans-XIV) that can be separated by crystallization. (trans-XIV) does not react with LTMP, but can be reverted to (XIII) with t-BuOK in order to increase the yield in (cis-XIV). On the other hand, the reaction of (cis-XIV) with LTMP and (+)-camphorsulfonyl oxaziridine (VII) affords a mixture of cis- and trans-hydroxy-oxolactones (cis-XV + trans-XV) that can be separated by chromatography. The reduction of (cis-XV) with Red-Al followed by a basic workup gives the alpha-diol with trans-configuration in the lactone ring (XVI), and the reduction of (trans-XV) with samarium diiodide affords the same alpha-diol isomer (XVI). This alpha-diol (XVI) is protected with COCl2 in pyridine to give the cyclic carbonate (XVII). (For the second part, see Holton, R.A. et al. J Amer Chem Soc 1994, 116(4): 1599).