BMS-247243 

BMS-247243 is a β-lactam antibiotic against methicillin-resistant Staphylococcus aureus. This section introduces its synthesis method and biological properties. A practical synthetic method was developed to exchange iodide ions with chloride ions to form 4-thiopyridinol 6b with C-3 side chain, thereby effectively synthesizing methyl ester 12b with C-7 side chain. The reaction of 14 with methylthiolate lithium salt was catalyzed by Bu4NCl to form methyl ester 12b in high yield. Reaction with thiolate dianion gave the corresponding Michael addition byproduct, resulting in a decrease in the quality of thermodynamic product 12b. The diester 17 was synthesized by acid chlorination acylation of 16 with 12b in a two-phase system, avoiding the troublesome deprotection work such as using DCC or EDAC. During the TFA reaction to remove the protecting group 17, the bis acid 20 was unexpectedly obtained. The bis acid 19 reacted with 4-thiopyridinol 6b to form BMS-247243 in moderate yield. Alternatively, efficient coupling of diester 17 with 4-thiopyridinol 6b afforded crystalline diester 21 with little contamination from isomer 22. Double deprotection of diester 21 followed by crystallization afforded the bis-zwitterion BMS-247243 in high yield.

838.84

C₃₆H₄₁Cl₂N₅O₈S₃

307316-55-8

[O-]C(C1=C(CSC2=CC(C)=[N+](CCC[N+]3(CCOCC3)C)C(C)=C2)CS[C@@]([C@@H]4NC(CSC5=C(C=C(C(Cl)=C5)/C=C/C(NCC([O-])=O)=O)Cl)=O)([H])N1C4=O)=O

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. A Practical Synthesis of an Anti-Methicillin Resistant Staphylococcus aureus Cephalosporin BMS-247243