Ketopantolactone enantioselective reduction

Despite the progress made in the stereoselective synthesis of (R)-pantothenic acid since the mid-1980s, the commercial chemical synthesis still involves resolution of racemic pantolactone. Recent (ca 1997) synthetic efforts have been directed toward developing a method for enantioselective synthesis of (R)-pantolactone by either chemical or microbial reduction of ketopantolactone. Microbial reduction of ketopantolactone is a promising area for future research. 

Enantioselective reduction of ketopantolactone and methyl benzoylformate was also examined by the same authors. Quite recently, Bakos and coworkers reported an enantioselective hydrogenation of dehydroalanine using an in situ-produced [Rh (COD)(S)-MonoPhos)2]Bp4 complex on AI2O3 [83,84]. After the optimization of the flow reaction conditions, a highly enantioselective production of (R)-acetylalanine methyl ester (>99% conversion and 96-97% ee) was achieved. 

In a first step, JS ocardia asteroides selectively oxidizes only (3)-pantolactone to ketopantolactone (19), whereas the (R)-pantolactone remains unaffected (47). The accumulated ketopantolactone is stereospecificaHy reduced to (R)-pantolactone in a second step with Candidaparapsilosis (product concentration 72 g/L, 90% molar yield and 100% ee) (48). Racemic pantolactone can also be converted to (R)-pantolactone by one single microbe, ie, Jiodococcus erythropolis by enantioselective oxidation to (3)-pantolactone and subsequent stereospecific reduction in 90% yield and 94% ee (product concentration 18 g/L) (40). 

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