Synthesis of isopenicillin derivatives in the absence of living cells

摘要

Isopenicillin derivatives having antimicrobial properties and a general formula of: where R, R1, and R2 are hydrogen, methyl, ethyl, propyl, isopropyl, or halogenated methyl, ethyl, propyl or isopropyl radicals and R3 is +TR are produced in a cell-free system using an extract from Cephalosporium acremonium. The starting materials for the synthesis consist of tripeptides composed of unsubstituted or beta -substituted D-valine, unsubstituted or substituted L cysteine, and L- alpha -aminoadipic acid or its analogues. Certain enzymes in the cell-free extract are inactivated so that conversion does not proceed past the isopenicillin stage.