113823-60-2

Upstream product

• 149-30-4 2-Mercaptobenzothiazole 
• 123285-25-6 diphenylmethyl (4R)-6,6-dibromo-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo<3.2.0>heptane-2-carboxylate 4-oxide 
• 100298-37-1 benzhydryl 6,6-dibromopenicillanate 1-oxide 

Downstream Products

• 137813-70-8 benzhydryl 2β-chloromethyl-6,6-dibromopenicillanate 1α-oxide 
• 137813-71-9 benzhydryl 2β-chloromethyl-6,6-dibromopenicillanate 1β-oxide 
• 137813-73-1 (R)-2-[(R)-2-(Benzothiazol-2-yldisulfanyl)-4-oxo-azetidin-1-yl]-3-chloromethyl-but-3-enoic acid benzhydryl ester 
• 137813-79-7 (2S,3R,5R)-3-Acetoxymethyl-3-chloromethyl-4,4,7-trioxo-4λ⁶-thia-1-aza-bicyclo[3.2.0]heptane-2-carboxylic acid benzhydryl ester 
• 137813-77-5 (2S,3S,5R)-3-Bromomethyl-3-chloromethyl-4,4,7-trioxo-4λ⁶-thia-1-aza-bicyclo[3.2.0]heptane-2-carboxylic acid benzhydryl ester 
• 137813-75-3 (2S,5R)-3,3-Bis-chloromethyl-4,4,7-trioxo-4λ⁶-thia-1-aza-bicyclo[3.2.0]heptane-2-carboxylic acid benzhydryl ester 
• 137813-78-6 (2S,3R,5R)-3-Acetoxymethyl-3-chloromethyl-7-oxo-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carboxylic acid benzhydryl ester 
• 137813-72-0 benzhydryl 2β-chloromethyl-6,6-dihydropenicillanate 1α-oxide 
• 137813-76-4 (2S,3S,5R)-3-Bromomethyl-3-chloromethyl-7-oxo-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carboxylic acid benzhydryl ester 
• 137813-74-2 (2S,5R)-3,3-Bis-chloromethyl-7-oxo-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carboxylic acid benzhydryl ester 
• 113823-59-9 benzhydryl 2β-chloromethyl-6,6-dibromopenicillanate 

Relevant academic research and scientific papers

Rational design of a β-lactamase inhibitor achieved via stabilization of the trans-enamine intermediate: 1.28 A crystal structure of wt SHV-1 complex with a penam sulfone

β-Lactamases are one of the major causes of antibiotic resistance in Gram negative bacteria. The continuing evolution of β-lactamases that are capable of hydrolyzing our most potent β-lactams presents a vexing clinical problem, in particular since a number of them are resistant to inhibitors. The efficient inhibition of these enzymes is therefore of great clinical importance. Building upon our previous structural studies that examined tazobactam trapped as a trans-enamine intermediate in a deacylation deficient SHV variant, we designed a novel penam sulfone derivative that forms a more stable trans-enamine intermediate. We report here the 1.28 A resolution crystal structure of wt SHV-1 in complex with a rationally designed penam sulfone, SA2-13. The compound is covalently bound to the active site of wt SHV-1 similar to tazobactam yet forms an additional salt-bridge with K234 and hydrogen bonds with S130 and T235 to stabilize the frans-enamine intermediate. Kinetic measurements show that SA2-13, once reacted with SHV-1 β-lactamase, is about 10-fold slower at being released from the enzyme compared to tazobactam. Stabilizing the trans-enamine intermediate represents a novel strategy for the rational design of mechanism-based class A β-lactamase inhibitors.

SYNTHESIS AND BETA-LACTAMASE INHIBITORY ACTIVITY OF 2,2-BIS(MONOSUBSTITUTED) METHYLPENICILLIN SULFONES

A series of 2,2-bis(monosubstituted) methylpenicillin sulfones were prepared from 6,6-dibromopenicillanate by a double sulfoxide rearrangement. β-Lactamase inhibitory activity of 2,2-bis(chloromethyl)penicillanic acid sulfone was studied and its activity