Two-phase synthesis of (−)-taxuyunnanine D

ABSTRACT: The first successful effort to replicate the beginning of the Taxol oxidase phase in the laboratory is reported, culminating in the total synthesis of taxuyunna-nine D, itself a natural product. Through a combination of computational modeling, reagent screening, and oxidation sequence analysis, the first three of eight C−H oxidations (at the allylic sites corresponding to C-5, C-10, and C-13) required to reach Taxol from taxadiene were accom-plished. This work lays a foundation for an eventual total synthesis of Taxol capable of delivering not only the natural product but also analogs inaccessible via bioengineering. Only eight C−H oxygenation events separate theminimally oxidized hydrocarbon taxadiene (1) from Taxol (2).1 Known by enzymologists as the oxidase phase, the approximate order of oxidation is proposed to occur at C-5, C