Lipase-catalyzed hydrolysis of (4-phenoxyphenoxy)propyl acetates for preparation of enantiomerically pure juvenile hormone analogues

Enzyme-catalyzed hydrolysis of 1-(4-phenoxyphenoxy)-2-propyl acetate (1a) was examined in a two-liquid phase reaction system of water and the insoluble substrate for the preparation of an enantiomerically pure juvenile hormone analogue (JHA). Almost all the lipases and the microorganisms tested hydrolyzed (R)-1a preferentially to afford (R)-1-(4-phenoxyphenoxy)-2-propanol (R)-2a. Pseudomonas cepacia lipase (PCL) showed the greatest enantioselectivity (E > 1,000) and the highest activity. Reaction performance by PCL was studied in some detail from the viewpoints of practical applications. A comparative study was also done of the hydrolysis of 2-(4-phenoxyphenoxy)-1-propyl acetate 1b. A few enzymes including PCL that exhibited great performances for 1a yielded (S)-alcohol and unhydrolyzed (R)-acetate with lower enantioselectivity and higher reaction rates. It was suggested that these results should he discussed from mechanistic standpoints of enzyme action and that steady-state kinetic studies on PCL-catalyzed hydrolysis of enantiomeric substrates might contribute to elucidate the enzyme specificity. An efficient biochemical process was described for the total conversion of 2a to (S)-2a for the preparation of the physiologically active form of the JNA (S)-pyriproxyfen. The process developed by a combination of lipase-catalyzed hydrolysis and chemical transformation was applicable to various secondary alcohols having a chiral center in the molecule once a highly enantioselective enzyme was found for the target alcohol. (C) 1997 by Elsevier Science Inc.