Taxol- phenylisoserine precursor

Synthesis of (2i ,3V)-Phenylisoserine Precursor of the Taxol and Taxotere Side Chains... 

Furthermore, two enantiocomplementary baker s yeast enzymes were also used for the reduction of an ct-chloro-jS-keto ester to yield precursors for both enantiomers of the N-benzoyl phenylisoserine Taxol side chain (Fig. 10.10). These results demonstrate the power of genomic fusion protein libraries to identify appropriate biocatalysts rapidly and expedite process development. ... 

Taxol, the drug of choice for treating certain types of ovarian and breast cancers, contains an N-benzoyl (2R,35)-phenylisoserine unit as the side chain. A precursor of the ethyl ester of this unit (2R,35)-135 is ethyl (25,3R)-2-chloro-3-hydroxy-3-phenylpropanoate 134 (Scheme 57.40), which has been prepared with very high yield (91 %) by means of the DYRKR of rac-133 mediated by the reductase YDL124w (a Saccharomyces cerevisiae reductase). " The facile enolization of the substrate under the reaction conditions (30°C, pH constant of 5.6) in addition... 

Another key precursor for the taxol semisynthetic process is the preparation of chiral C-13 taxol side chain. Two different stereoselective enzymatic processes were developed for the preparation of chiral C-13 taxol side chain syntiion [51-54]. In one process, the stereoselective microbial reduction of 2-keto-3-(iV-benzoylamino)-3-phenylpropionic acid ethyl ester 40 to yield (2/ ,5S)-(—)-iV-benzoyl-3-phenylisoserine ethyl ester 41a was dem-... 

---