129792-01-4Relevant academic research and scientific papers
A new synthesis of 6-oxopenicillanates by ozonolysis of 6-diazopenicillanates
Ursini,Pellicciari,Tamburini,Carlesso,Gaviraghi
, p. 363 - 364 (1992)
In this paper we describe a convenient new procedure for preparing 6-oxopenicillanates, via ozonization of the corresponding 6-diazo derivatives.
BETA-LACTAMASE INHIBITORY COMPOUNDS
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Page/Page column 48, (2010/02/17)
Inhibitors of the enzyme beta-lactamase are provided. The compounds are adapted to inhibit beta-lactamase as produced by beta-lactam resistant bacterial strains. Methods of treatment of beta-lactam resistant bacterial infections in patients are provided.
Design, synthesis, and crystal structures of 6-alkylidene-2′- substituted penicillanic acid sulfones as potent inhibitors of acinetobacter baumannii OXA-24 carbapenemase
Bou, German,Santillana, Elena,Sheri, Anjaneyulu,Beceiro, Alejandro,Sampson, Jared M.,Kalp, Matthew,Bethel, Christopher R.,Distler, Anne M.,Drawz, Sarah M.,Pagadala, Sundar Ram Reddy,Van Den Akker, Focco,Bonomo, Robert A.,Romero, Antonio,Buynak, John D.
supporting information; scheme or table, p. 13320 - 13331 (2010/12/18)
Class D β-lactamases represent a growing and diverse class of penicillin-inactivating enzymes that are usually resistant to commercial β-lactamase inhibitors. As many such enzymes are found in multi-drug resistant (MDR) Acinetobacter baumannii and Pseudomonas aeruginosa, novel β-lactamase inhibitors are urgently needed. Five unique 6-alkylidene-2′-substituted penicillanic acid sulfones (1-5) were synthesized and tested against OXA-24, a clinically important β-lactamase that inactivates carbapenems and is found in A. baumannii. Based upon the roles Tyr112 and Met223 play in the OXA-24 β-lactamase, we also engineered two variants (Tyr112Ala and Tyr112Ala,Met223Ala) to test the hypothesis that the hydrophobic tunnel formed by these residues influences inhibitor recognition. IC50 values against OXA-24 and two OXA-24 β-lactamase variants ranged from 10 ± 1 (4 vs WT) to 338 ± 20 nM (5 vs Tyr112Ala, Met223Ala). Compound 4 possessed the lowest Ki (500 ± 80 nM vs WT), and 1 possessed the highest inactivation efficiency (kinact/ Ki = 0.21 ± 0.02 μM-1 s-1). Electrospray ionization mass spectrometry revealed a single covalent adduct, suggesting the formation of an acyl-enzyme intermediate. X-ray structures of OXA-24 complexed to four inhibitors (2.0-2.6 A) reveal the formation of stable bicyclic aromatic intermediates with their carbonyl oxygen in the oxyanion hole. These data provide the first structural evidence that 6-alkylidene-2′-substituted penicillin sulfones are effective mechanism-based inactivators of class D β-lactamases. Their unique chemistry makes them developmental candidates. Mechanisms for class D hydrolysis and inhibition are discussed, and a pathway for the evolution of the BlaR1 sensor of Staphylococcus aureus to the class D β-lactamases is proposed.
Penicillins as β-lactamase-dependent prodrugs: Enabling role of a vinyl ester exocyclic to the lactam ring
Ruddle, Carol C.,Smyth, Timothy P.
, p. 2332 - 2333 (2007/10/03)
Incorporation of a vinyl ester exocyclic to the β-lactam ring of a penicillin nucleus enables this to act as a β-lactamase-dependent prodrug - rapid release of the (unactivated) alkoxy component of the vinyl ester is triggered by enzyme-catalysed hydrolys
Process for the preparation of α-oxolactams
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, (2008/06/13)
A method for preparing an α-oxolactam comprising, reacting a corresponding α-diazolactam with an oxygen donor, in the presence of a transition metal catalyst, to yield the corresponding α-oxolactam.
The synthesis and evaluation of 6-alkylidene-2'β-substituted penam sulfones as β-lactamase inhibitors
Buynak, John D.,A Srinivasa, Rao,Doppalapudi, Venkata Ramana,Adam, Greg,Petersen, Peter J.,Nidamarthy, Sirishkumar D.
, p. 1997 - 2002 (2007/10/03)
Penicillin sulfones, which structurally incorporate both a 6-position alkylidene substituent and a 2'β substituent, have been synthesized and evaluated as inhibitors of class C and class A serine β-lactamases. Incorporation of the 2'β-substituent generall
A convenient method for the production of 6-oxopenicillinates and 7- oxocephalosporinates
Buynak, John D.,Rao, A. Srinivasa,Nidamarthy, Sirishkumar D.
, p. 4945 - 4946 (2007/10/03)
A convenient and economical method for the preparation of 6- oxopenicillinates and 7-oxocephalosporinates from the corresponding amines is presented. These ketones are key intermediates in the synthesis of inhibitors of β-lactamase and elastase.
Synthesis of 6-Vinylidenepenams
Buynak, John D.,Borate, H. B.,Lamb, Grady W.,Khasnis, Dipti D.,Husting, Chad,et al.
, p. 1325 - 1335 (2007/10/02)
The preparation of unique penicillin derivatives containing an exocyclic allene at the 6 position (6-vinylidenepenams) is described.The synthetic scheme utilizes 6-oxopenicillinates as intermediates which stereospecifically add acetylide anions forming pr
