36923-27-0

Upstream product

• 35500-75-5 (1R)-3-phenoxymethyl-(1rH,5cH)-4-thia-2,6-diaza-bicyclo[3.2.0]hept-2-en-7-one 
• 59203-76-8 (R)-3-methyl-2-((1R)-7-oxo-3-phenoxymethyl-(1rH,5cH)-4-thia-2,6-diaza-bicyclo[3.2.0]hept-2-en-6-yl)-but-3-enoic acid methyl ester 
• 2315-05-1 methyl (2S,5R,6R)-3,3-dimethyl-7-oxo-6-(2-phenoxyacetamido)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate 
• 380412-96-4 (4S,6R,7R)-4-Hydroxy-8-oxo-7-(2-phenoxy-acetylamino)-5-thia-1-aza-bicyclo[4.2.0]octane-2,2-dicarboxylic acid dimethyl ester 
• 147162-34-3 2-Allyl-2-((1R,5R)-7-oxo-3-phenoxymethyl-4-thia-2,6-diaza-bicyclo[3.2.0]hept-2-en-6-yl)-malonic acid dimethyl ester 
• 380412-95-3 2-(2-Oxo-ethyl)-2-((1R,5R)-7-oxo-3-phenoxymethyl-4-thia-2,6-diaza-bicyclo[3.2.0]hept-2-en-6-yl)-malonic acid dimethyl ester 
• 147162-33-2 2-((1R,5R)-7-Oxo-3-phenoxymethyl-4-thia-2,6-diaza-bicyclo[3.2.0]hept-2-en-6-yl)-malonic acid dimethyl ester 
• 132-98-9 penicillin V potassium 
• 10209-03-7 methyl 6β-phenoxyacetamidopenicillanate-1β-sulfoxide 
• 380412-94-2 3-methyl-2-((1R)-7-oxo-3-phenoxymethyl-(1rH,5cH)-4-thia-2,6-diaza-bicyclo[3.2.0]hept-2-en-6-yl)-but-2-enoic acid methyl ester 
• 380412-97-5 (6R,7R)-8-Oxo-7-(2-phenoxy-acetylamino)-5-thia-1-aza-bicyclo[4.2.0]oct-3-ene-2,2-dicarboxylic acid dimethyl ester 
• 64836-37-9 p-nitrobenzyl (2R,3R)-7-phenoxyacetylaminoceph-3-em-4-carboxylate 

Relevant academic research and scientific papers

Synthesis and decarboxylation of Δ2-cephem-4,4-dicarboxylic acids

Penicillin V was converted in 14 steps into Δ2-cephems having hydrogen at C-3, hydrogen or methyl at C-2, and two methoxycarbonyl, two benzyloxycarbonyl, or one methoxycarbonyl and one benzyloxycarbonyl substituent at C-4. Deprotection of these Δ2-cephem-4,4-dicarboxylic acid esters by alkaline hydrolysis (in the case of methyl esters) or hydrogenolysis (in the case of benzyl esters) led in all cases to rapid decarboxylation of the Δ2-cephem-4,4-dicarboxylic acid or Δ2-cephem-4,4-dicarboxylic acid monoester. With hydrogen at C-2, hydrolysis of the dimethyl ester with 1 equiv of base produced a Δ2-cephem. With 2 equiv of base, and with all compounds having methyl at C-2, hydrolysis or hydrogenolysis afforded 4α-substituted-Δ2-cephems. In contrast, simpler benzyl or methyl acetamidomalonates could be deprotected without difficulty to afford stable malonic acids. Reasons for the differences in ease of decarboxylation were examined using semiempirical (AM1) and ab initio (3-21G) molecular orbital calculations. The decarboxylation barriers of unionized cephem or acetamido malonic acids were found to be high (35-40 kcal mol-1). Although the monoanion of acetamidomalonic acid retained a high barrier, the epimeric monoanions of a Δ2-cephem malonic acid decarboxylated with barriers of only 2 kcal mol-1.

A New Preparative Route to 3-Unsubstituted Cephalosporins from Penicillin V

p-Nitrobenzyl (2R,3R)-2-(benzothiazol-2'-yldithio)-α-isopropylidene-4-oxo-3-phenoxyacetylaminoazetidine-1-acetate (7), readily prepared from penicillin V, can be converted into the corresponding 2-allylthio compound (2) by addition of allyl bromide and sodium borohydride at a low temperature.This compound (2) on treatment with ozone, followed by cyclization with trimethyl phosphite, produces a 3H-ceph-3-em ester (4).The ester can be easily de-esterified to the free acid (1b).