CHEMOENZYMATIC SYNTHESIS OF 4 DIASTEREOMERS OF (6-FLUORO-2-CHROMANYL)OXIRANE - AN INTERMEDIATE OF A POTENT BETA-BLOCKER

The synthesis of optically active 5-acetoxy-3-(p-fluorophenoxy)-1-pent anol 4, for the synthesis of the potent beta-blocker R-67555, bis[2-(2 -chromanyl-6-fluoro)-2-hydroxyethyl]amine 1, was investigated. The ace tylation of 3-(p-fluorophenoxy)-1,5-pentanediol 5a using lipozyme and the hydrolysis of 1,5-diacetoxy-3-(p-fluorophenoxy)pentane 5b using li pase Amano P yielded (3S)- and (3R)-5-acetoxy-3-(p-fluorophenoxy)-1-pe ntanol 4, respectively, with high enantiomeric excess. Four diastereom ers of (6-fluoro-2-chromanyl)oxirane 2, important intermediates for th e synthesis of R-67555, were synthesized by chemical methods using (S) -4 and (R)-4. (C) 1997 Published by Elsevier Science B.V.