Penam carboxylic acid synthesis

Penam Sulfone B-Lactamase Inhibitors. Natural product discoveries stimulated the rational design of p-lactamase inhibitors based on the readily accessible penicillin nucleus. An early success was penicillanic acid sulfone, (2(5)-cis)-3,3-dimethyl-7-oxo-4,4-dioxide-4-thia-l-a2abicyclo [3.2.0]heptane-2-carboxylic acid [68373-14-8] (sulbactam) (25, R = = H, R" = R" = CH ), CgH NO S. The synthesis (118), microbiology (119—121),... 

The synthesis of tazobactam from 6-APA (Scheme 6.15) proceeded via the 2- -(chloromethyl)penam ester (81 a), which was first prepared by Gottstein and co-workers [47] during the synthesis of 2-/S-(chloromethyl)-2-a-methylpenam-3a-carboxylic acid 1,1-dioxide (29). 6-APA (8) was converted to 6a-bromopenicillanic acid (77) by treatment with sodium nitrite and hydrobromic acid. Oxidation with peracetic acid in the presence of benzophenone hydrazone gave benzhydryl 6a-bromopenicillanate-l-oxide (78) and reduction with zinc and acetic acid gave benzhydryl penicillanate-1-oxide (79). The unsymmetrical azetidinone disulphide (80) was obtained by heating with 2-mercaptobenzothiazole reaction with copper (II) chloride... 

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