Carbapenam derivatives synthesis

Since we were unable to obtain the succinaldehyde derivatives, e.g. 38 (ref. 26) that are needed for the above carbapenam derivatives, we confined ourselves to model experiments with malonaldehyde dimethyl acetal (ref. 23). In the meantime, we have found a convenient synthesis for succinal-dehyde diethyl acetal 38 (Scheme 8). Thus we now are able to continue our carbapenem syntheses via the cycloadducts 40. 

Schane 3.34 Synthesis of a carbapenam derivative via Suzuki-Miyaura cross-coupling. 

The synthesis of the carbapenam-3-carboxylic acid 36 <03JA15746> as well as a study on carbapenem biosynthesis have been documented <03JA8486>. The cephalosporin derivative 37 has been prepared and its use as a novel fluorogenic substrate for imaging P-lactamase gene expression demonstrated <03JA11146>. The nucleus of the carbacephem antibiotic loracarbef has been synthesized in a highly efficient and enantioselective fashion from 25,3iS-2-amino-3-hydroxy-6-heptenoic acid, which was derived from enzyme-catalyzed... 

A method for the enantioselective synthesis of the ftmctionalised carbapenam core 38 from D-serine-derived pyrrolidines has been reported <03JOC187>. Disubstituted pyrrolidines, obtained from the retro Dieckmann reaction of azabicyclo[2.2.1]heptan-2-one-1-carboxylic acid methyl esters, have been used as starting materials to develop concise syntheses of all four stereoisomers of carbapenam-3-carboxylic acid methyl esters <03JOC2889>. The synthesis of 1-methylcarbapenams 39 by intramolecular attack of lactam nitrogen on a 77 -propargylpalladium complex has been reported <03JOC8068>. 

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