Dr. Sari Deketelaere, Dr. Carlos Díez-Poza, Margot Aelbrecht, Jonas Mortier, Bram Van Den Bossche, Dr. Jorick Franceus, Prof. Dr. Tom Desmet, Prof. Dr. Kristof Van Hecke, Prof. Dr. Christian V. Stevens, Prof. Dr. Matthias D'hooghe
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Synthesis of Pyrrolidine-fused β-lactams as Potential β-lactamase Inhibitors
A synthetic protocol for the preparation of novel 3,4-pyrrolidine-fused β-lactams was developed. The proposed 2,6-diazabicyclo[3.2.0]heptan-7-one scaffolds were constructed through an amido group-induced, potassium tert-butoxide-promoted intramolecular ring closure of 3-acylamino-4-oxiranyl-β-lactams as the key reaction step. Alternatively, the desired cyclization was also effected by means of a scandium triflate-mediated catalytic approach. In this way, a set of stereodefined 3,4-pyrrolidine-fused β-lactams was synthesized, which were preliminary evaluated as β-lactamase inhibitors. These first-line biological assessments led to the identification of a 2-benzoyl-6-(4-methoxyphenyl)-substituted diazabicyclo structure as an eligible starting point for further β-lactamase inhibitor optimization studies.
期刊介绍:
Organic chemistry is the fundamental science that stands at the heart of chemistry, biology, and materials science. Research in these areas is vigorous and truly international, with three major regions making almost equal contributions: America, Europe and Asia. Asia now has its own top international organic chemistry journal—the Asian Journal of Organic Chemistry (AsianJOC)
The AsianJOC is designed to be a top-ranked international research journal and publishes primary research as well as critical secondary information from authors across the world. The journal covers organic chemistry in its entirety. Authors and readers come from academia, the chemical industry, and government laboratories.