MRSA carbapenem

The first time we encountered the Sugasawa reaction was in the early 1990s, when we worked on anti-MRSA carbapenem projects. We were very interested in this... 

Design and Development of Practical Syntheses of MRSA Carbapenems... 

Process research efforts relative to the design of a practical synthesis of a structurally complex MRSA carbapenem (1) culminated in the establishment of two distinct synAeses. The first is based on a unique Stille coupling between a carbapenem enol triflate and a stannatrane appended via a methylene spacer to a complex and extended heteroaromatic side chain. The second is founded upon a novel n-allyl palladium reaction to incorporate die entire complex side chain. Details on die development of both methods are described. 

Figure 2, Medicinal chemistry route to the MRSA carbapenem.

Local treatment of skin and soft tissue infections with antibiotic-containing ointments or solutions should not be used because it leads to allergic reactions and rapid development of bacterial resistance. In settings where MRSA or resistant Enterobacte-riaceae (like ESBL s gram negative bacteria with extended spectrum beta lactames) or Pseudomonas spp. occur, the empiric use of vancomycin and a carbapenem can be necessary. The risk of transmission of these organisms should be minimalised by hygienic and isolation measures. 

Activated sulfonamides and other activated amines were used in a series of Mitsunobu reactions to prepare analogs of 2-(sulfanamido)methyl carbapenems (124) as potential anti-MRSA compounds. The basic reaction scheme and some of the activated amines that were used are shown in the figure below. Additional examples can be found in the original paper. 

Empiric therapy should be tailored to each institution s resistance profile, but usually will include vancomycin (or cefazolin if low prevalence of MRSA) plus another antibiotic with Gram-negative coverage (e.g., third-generation cephalosporin, carbapenem, or p-lactam/p-lactamase inhibitor). If methicillin-susceptible S. aureus is found as the causative pathogen, then cefazolin or flucloxa-cillin/oxacillin should be the treatment of choice. In general, we prefer antibiotics that need to be administered after dialysis only. The most commonly utilized postdialysis antibiotic regimens include vancomycin, teicoplanin, cefazolin. 

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