A Catalytic Asymmetric Route to Carbapenems

Abstract

Efficient syntheses of N-acetyl thienamycin and epithienamycin A in readily deprotected form are reported where three contiguous stereocenters are established in a single catalytic asymmetric azetidinone-forming reaction. These examples are a template for synthesizing C5/C6 cis or trans carbapenems with independent control of the C8 stereocenter. A library of oxidatively and sterochemically defined azetidinone precursors to a variety of naturally-occurring carbapenems and potential biosynthetic intermediates has been prepared to facilitate studies of carbapenem antibiotic biosynthesis.

Recent advances in the chemoselective reduction of functional groups mediated by samarium(ii) iodide: a single electron transfer approach

“…Several other noteworthy applications are listed in the reference section. [163][164][165][166][167]…”

New Directions in Ketene Chemistry: The Land of Opportunity

“…This methodology was originally developed for thestereoselective synthesis of β‐lactams with use of a chiral nucleophilic catalyst and kinetic base together with Et 3 N as a stoichiometric base, enhanced by an additional electrophilic catalyst. In a recent application the β‐lactam 2 (Scheme ) was prepared and used in a synthesis of thecarbapenem N ‐acetylthienamycin 3b. Ketenes are known to be formed as observable intermediates under similar conditions,2b but just as in Scheme a ketene enolate is involved in the step in which the stereochemistry of the product 2 is determined.…”

Non-Heme Iron Oxygenases Generate Natural Structural Diversity in Carbapenem Antibiotics

“…The first method provided the trans (3 S ,4 R )-configuration by alkylating the enolate of an azetidinone derived from L-aspartic acid 12. The second method employed a catalytic asymmetric azetidinone-forming reaction that produced either enantiomer of the cis 3,4-disubstituted azetidinones with independent control of the carbapenem C-8 sterocenter 13. These compounds could be used as precursors of cis or trans carbapenems.…”