Hansenula fabianii

Another enzymatic approach to obtain the desired stereochemistry in the side chain is shown in Scheme 17.13. The keto ester precursor 10 of the side chain ethyl ester can be reduced to the hydroxy (2R,3S) ester 11 using either of the yeasts Hansenula polymorpha SC 13865 or Hansenula fabianii SC 13894. Screening a variety of strains from our cultme collection revealed many other strains that could carry out the reduction reaction, but the best yields and ee s using whole cells were obtained with the two strains of Hansenula. Of four possible reduction products, the desired product 11 is obtained with 95 to 99% ee and 80 to 90% yield. Because of rapid ketone/enol tautomerism, the enzymatic reduction can work as a dynamic resolution and fix the stereochemistry at both the 2- and 3-positions. 

Figure ll.lOf shows the synthesis of chiral C-13 paclitaxel side chain, key precursor for the paclitaxel S5mthetic process by a preparative-scale reduction of aminoketoester by Hansenula fabianii SC 13894 2R,3S)- N-benzoyl-3-phenylisoserine ethyl ester was obtained in 88% yield with 95% ee [63]. 

SCHEME 33.12. Synthesis of paclitaxel side chain using reduction of aminoketoester with Hansenula fabianii SC 13894. 

Hat-shaped ascospores Hansenula anomala fabianii jadinii... 

Hansenula (anomala, fabianii, jadinii) b No ascospore formation. 

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