Efficient and practical synthesis of a potent anti-MRSA beta-methylcarbapenem containing a releasable side chain

Humphrey GR; Miller RA; Pye PJ; Rossen K; Reamer RA; Maliakal A; Ceglia SS; Grabowski EJJ; Volante RP; Reider PJ

Journal of the American Chemical Society, Vol.121, No.49, 11261-11266, 1999

Humphrey GR, Miller RA, Pye PJ, Rossen K, Reamer RA, Maliakal A, Ceglia SS, Grabowski EJJ, Volante RP, Reider PJ

We describe a convergent synthesis of the MRSA beta-methyl carbapenem 1, wherein the molecule is assembled from the naphthosultam side chain 2 and the allylic carbonate of the beta-Me carbapenem piece 6. The beta-Me stereochemistry of 6 is set up in a novel titanium enolate addition into the TBDMS acetoxy azetidinone 5. The benzenesulfonate salt of 1 is endowed with exceptional stability.