合成路线1

A new total synthesis of paclitaxel has been described: This synthesis starts from 2-methyl-2-(3-oxobutyl)cyclohexane-1,3-dione (I), which by a multistep synthesis (Helv Chim Acta 1950, 33: 2215) yields (S)-Wieland Miesher ketone (II). This compound is converted by a known process (J Org Chem 1992, 57: 3274) to the ketal (III), which by reaction with trimethylsulfonium iodide and potassium hexamethyldisilazide (KHMDS) affords the hydromethyl derivative (IV). The cyclization of (IV) according to J Org Chem 1992, 57: 3274 yields the oxetane derivative (V), which is benzylated and deprotected, affording the ketone (VI). A multistep ring cleavage of (VI) according to Angew Chem Int Ed Engl 1995, 34: 452 gives the aldehyde (VII), which is condensed with the lithium compound (VIII) (obtained from the corresponding iodo compound (IX) and BuLi) to afford the dienic ketone (X). The epoxidation of (X) with m-chloroperbenzoic acid (m-CPBA) followed by reduction with H2 over Pd/C yields compound (XI) with a tertiary hydroxy group, which by reaction with carbonyl diimidazole (CDI) and NaH affords the cyclic carbonate (XII). The reduction of (XII) with L-selectride in THF gives the saturated ketone (XIII), which is converted to the corresponding vinyl trifluoromethanesulfonate (XIV) by known methods. The cleavage of the dimethyl acetal group with pyridinium p-toluenesulfonate (PPTS) followed by chain elongation with methylenetriphenylphosphorane affords the allyl derivative (XV), which is submitted to cyclization with palladium triphenylphosphine complex, affording compound (XVI) with the basic ring system of paclitaxel. The previous change of the tert-butyldimethylsilyl (TBDMS) protecting group to a triethylsilyl (TES) group (less difficult to remove when the functionality of the tetracyclic structure is more complex) is performed with tetrabutylammonium fluoride (TBAF) and TES-Tf, yielding compound (XVII). The epoxidation of (XVII) with m-CPBA as usual affords epoxide (XVIII).