Hans-Eckart Radunz

A CONVENIENT APPROACH TO HYDROXYETHYLENE DIPEPTIDE ISOSTERES AS BUILDING BLOCKS FOR ENZYME INHIBITORS

Abstract γ-Lactones 6,8,10 and the ester 9, precursors to the hydroxyethylene dipeptide isostere unit, were synthesized stereoselectively in two or three steps from α-amino-ketones in good yield. Peptides containing these isosteres are potent inhibitors of certain aspartyl proteinases. Alkylation of the (3S,4S)-substituted γ-lactone 6 afforded exclusively cis-alkylation, with regard to C-2 and C-4.

Microbial metabolism of the \-adrenoreceptor antagonist bisoprolol

Eighteen filamentous fungi and six actinomycetes species were screened for their ability to metabolize bisoprolol, a \-blocking drug. All strains of Cunninghamella tested accumulated metabolite M4 = EMD 46193 ([4-(2-hydroxy-3-isopropylaminopropoxy)benzyloxy]ethanol). Among the strains investigated only Gliocladium deliquescens excreted the corresponding carbonic acid M1 = EMD 44025 into the culture medium. Biotransformation of bisoprolol by fungi occurred only during growth in complex medium or with resting cells after cultivation in complex medium. The screened Actinomycetes showed no biotransformation of the drug.