A Versatile Strategy for the Solid-Phase Synthesis of Penicillin Derivatives: Efficient Preparation of 2β-Methyl Substituted Penams as β-Lactamase Inhibitor Analogues

Abstract

A convenient solid-phase method for the synthesis of 2β-methyl substituted penicillins using commercially available resins is described. Functionalization of Merrifield and Wang resin bound penam derivatives was performed by penicillin sulfoxide rearrangement and the products were released from the supports under mild conditions. The utility of this methodology has been demonstrated by synthesizing a small library of penicillin derivatives in moderate to very good overall isolated yields for the multistep synthetic sequence.

Key words

solid-phase synthesis - combinatorial chemistry - penicillins - rearrangement - sulfoxides

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22

Oxidation of resin-bound 2β-(heterocyclyl)thiomethyl penicillins to the corresponding sulfones was not carried out; however, this reaction is expected to be difficult to achieve due to the presence of two or more sulfur atoms in the molecule.