A chemoenzymatic approach to the synthesis of the stereoisomers of a beta-adrenergic receptor antagonist

The four stereoisomers of Delta(2)-isoxazoline 2, a beta-adrenergic recepto r antagonist structurally related to Falintolol i, were prepared by an enzy me-catalyzed kinetic resolution of the unsaturated secondary alcohol (+/-)- 7 followed by its cycloaddition to pyruvonitrile oxide. Through this strate gy, diastereomeric aminoalcohols (+)-2a/(-)-2b and (-)-2a/(c)-2b were obtai ned in 99 and 92% enantiomeric excess, respectively. The absolute configura tion to the target compounds was assigned via chemical correlation to the e nantiomers of epoxides 4a and 4b, whose stereochemistry had been previously established. (C) 2000 Elsevier Science Ltd. All rights reserved.