Pseudomonas cepacia lipase enantioselective acylation using

A chemoenzymatic methodology has been developed using indium-mediated allylation (and propargylation) of heterocyclic aldehydes under aqueous conditions followed by Pseudomonas cepacia lipase-catalyzed enantioselective acylation of racemic homoallylic and homo-propargylic alcohols in organic media.192... 

The natural products epothilone A and B are structurally different from taxol but have similar anticancer activity. Significantly, they have been reported to be much more active against cell lines exhibiting multiple-drug resistance [26], Taylor and co-workers at the University of Notre Dame have recently published an elegant, formal total synthesis of epothilone A [27], In this work, the authors used the CLC form of Burkholderia cepacia (formerly Pseudomonas cepacia) lipase (ChiroCLEC -PC) to resolve a key alcohol intermediate by selective acylation with vinyl acetate in /-butyl methyl ether (Fig. 6). The enantioselectivity was >20 1 at 47% conversion and efficiently provided gram quantities of the desired (R) alcohol. Since the unreacted (S) alcohol can easily be epimerized by a simple oxidation-reduction sequence and the catalyst reused without significant loss in activity, the method is ideally suited for scale-up. 

In an alternate process, enantioselective enzymatic acylation of racemic a-methyl-l,3-benzodioxole-5-ethanol (55, Fig. 17) was developed using Amano lipase PS-30 (lipase from Pseudomonas cepacia) with vinyl acetate as acylating agent in n-hexane benzene (2 1). This process gave (+)-56 in 54% yield with 80% ee and (-)-57 in 46% yield with 96% ee After separation of alcohol (+)-56 from acetate (-)-57 by methanolysis in the presence of K2CC)3, the acetate was converted to alcohol (-)-56 in 95% yield with 96% ee Mitsunobu inversion of (-)-56 provided (+)-56 in 94% yield with 96% ee The conversion of (.S )-alcohol 56 to (-)-talampanel was carried out in 54% overall yield (Easwar and Argade, 2003). 

In addition, Itoh and coworkers have reported that acylation of the alcohol was accomplished by three types of enzymes Candida Antarctica lipase (CAL, Novozym 435), lipase QL Alcalgenes sp.), and lipase PS Pseudomonas cepacia). Scheme 10.5. The desired acetate showed extremely high enantioselectivity, but no reaction took place when lipase (CRL, Candida rugosa) or Procine liver lipase (PPL) was used as the catalyst in the ionic liquid (Table 10.3). 

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