24138-28-1

Usage

Uses

Used in Pharmaceutical Industry:
[2S-(2alpha,5alpha,6alpha)]-6-bromo-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid is used as an intermediate in the synthesis of Tazobactam Sodium Salt-13C2,15N1. [2S-(2alpha,5alpha,6alpha)]-6-bromo-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid is a labeled analogue of Tazobactam Sodium Salt (T010100), which is a β-Lactamase inhibitor. It is commonly used in combination with β-lactam antibiotics to enhance their effectiveness by inhibiting the action of β-lactamase enzymes, which can break down and render the antibiotics ineffective.

Upstream product

• 551-16-6 6-Aminopenicillanic Acid 
• 24158-88-1 6,6-dibromopenicillanic acid 
• 21794-93-4 6-aminopenicillanic acid 
• 24158-88-1 6,6-Dibromopenicillanic acid 
• 551-16-6 6-aminopenicillanic acid 

Downstream Products

• 62263-89-2 Benzyl 6α-bromopenicillanate 
• 26631-90-3 brobactam 
• 87-53-6 penicillanic acid 
• 74189-25-6 diphenylmethyl 6α-bromopenicillanate 
• 100239-31-4 p-nitrobenzyl 6-bromopenicillanate 
• 122661-93-2 2α-methyl-2β-[(1,2,3-triazol-1-yl)methyl]penicillin-3α-carboxylic acid diphenylmethyl ester 
• 85573-72-4 (R)-2-[2-(benzothiazol-2-yldisulfanyl)-4-oxo-azetidin-1-yl]-3-methyl-butyl-3-enoic acid benzhydryl ester 
• 89786-04-9 tazobactam 
• 87579-78-0 diphenylmethyl (2S,5R,6R)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate 4-oxide 
• 80353-26-0 6α-bromopenicillan-3α-carboxylic acid diphenylmethyl ester-1β-oxide 
• 62263-72-3 (2S,5R)-Benzyl 3,3-Dimethyl-7-oxo-4-thia-1-azabicyclo<3.2.0>heptane-2-carboxylate 
• 73968-83-9 benzhydryl 6,6-dihydropenicillate 
• 76946-53-7 (2S,4R,5R)-3,3-Dimethyl-4,7-dioxo-4λ⁴-thia-1-aza-bicyclo[3.2.0]heptane-2-carboxylic acid benzyl ester 
• 303730-72-5 benzyl (2S)-2-[(4S)-4-chloro-2-oxazetidin-1-yl]-2-(1-chlorothio-1-methylethyl)-acetate 

Relevant academic research and scientific papers

Application of Continuous Flow in Tazobactam Synthesis

Tazobactam is a β-lactamase inhibitor. In this work, a combination of continuous flow and batch experiments for the synthesis of tazobactam has been developed. The first three steps and the preparation of the peroxyacetic acid are continuously carried out in the microreactors, which improves the procedure safety and efficiency. There is also a final step of the deprotection reaction in the microreactor, which can increase the yield and reduce the formation of impurities. Under optimized process conditions, the total yield of the target product reached 37.09% (30.93% in batch). The continuous flow method not only greatly reduces the reaction time but also significantly improves procedure safety and increases the yield.

Crystal structures of KPC-2 β-lactamase in complex with 3-nitrophenyl boronic acid and the penam sulfone PSR-3-226

Class A carbapenemases are a major threat to the potency of carbapenem antibiotics. A widespread carbapenemase, KPC-2, is not easily inhibited by β-lactamase inhibitors (i.e., clavulanic acid, sulbactam, and tazobactam). To explore different mechanisms of inhibition of KPC-2, we determined the crystal structures of KPC-2 with two β-lactamase inhibitors that follow different inactivation pathways and kinetics. The first complex is that of a small boronic acid compound, 3-nitrophenyl boronic acid (3-NPBA), bound to KPC-2 with 1.62-A resolution. 3-NPBA demonstrated a Km value of 1.0±0.1 μM (mean±standard error) for KPC-2 and blocks the active site by making a reversible covalent interaction with the catalytic S70 residue. The two boron hydroxyl atoms of 3-NPBA are positioned in the oxyanion hole and the deacylation water pocket, respectively. In addition, the aromatic ring of 3-NPBA provides an edge-to-face interaction with W105 in the active site. The structure of KPC-2 with the penam sulfone PSR-3-226 was determined at 1.26-A resolution. PSR-3-226 displayed a Km value of 3.8±0.4 μM for KPC-2, and the inactivation rate constant (k inact) was 0.034±0.003 s-1. When covalently bound to S70, PSR-3-226 forms a trans-enamine intermediate in the KPC-2 active site. The predominant active site interactions are generated via the carbonyl oxygen, which resides in the oxyanion hole, and the carboxyl moiety of PSR-3-226, which interacts with N132, N170, and E166. 3-NPBA and PSR-3-226 are the first β-lactamase inhibitors to be trapped as an acyl-enzyme complex with KPC-2. The structural and inhibitory insights gained here could aid in the design of potent KPC-2 inhibitors. Copyright

Process for preparation of penam derivatives

The invention relates to novel processes for preparing penam derivatives, such as Tazobactam and derivatives thereof. The processes according to the invention encompass procedures for the protection and deprotection of the carboxylic group as well as for the oxidation of the sulphur moiety of penam derivatives. Additionally, the present invention relates to new intermediates for the production of penam derivatives, allowing the desired penam-derivatives to be formulated with high purity and in good yields.

A new approach to the synthesis of tazobactam using an organosilver compound

Tazobactam (9) was synthesized in 8 steps from the readily accessible 6-APA. By the first use of silver triazole as reactant, the formation of the isomer 7 was avoided and a total yield of 50%, which was two to three times higher than that of reported procedures for 9, was obtained. Georg Thieme Verlag Stuttgart.

PROCESS FOR PREPARING 6-ALKYLIDENE PENEM DERIVATIVES

The present invention provides a process of making compounds of Formula (I), which are useful for the treatment of bacterial infection or disease.

Synthesis of (5R)-(Z)-6-(1-Methyl-1,2,3-triazol-4-ylmethylene)penem-3-carboxylic Acid, a Potent Broad Spectrum β-Lactamase Inhibitor, from 6-Aminopenicillamic Acid

(5R)-(Z)-6-(1-Methyl-1,2,3-triazol-4-ylmethylene)penem-3-carboxylic acid 34 (BRL 42715) has been prepared from 6-aminopenicillanic acid 4 (6-APA) by short stereoselective and efficient route via the novel intermediate, p-methoxybenzyl (5R,6S)-6-bromopenem-3-carboxylate 17.Elaboration of 6-APA 4 to the azetidinone disulfide 10 by established methodology, followed by reductive formylation provided the crystalline C-4 formylthio-azetidinone derivative 29.Cyclization of the oxalimide 28, obtained by ozonolysis of the formylthio derivative 29, to the crystalline 6α-bromopenem ester 17 was effected by way of the phosphine-mediated carbonyl-carbonyl coupling reaction.Sequential tretment of bromopenem 17 with lithium diphenylamide, 1-methyl-1,2,3-triazole-4-carbaldehyde, and acetic anhydride gave a diastereomeric mixture of acylated bromohydrins 32; reductive elimination of this mixture afforded a separable mixture of (Z)- and (E)-triazolylmethylenepenem esters, 33 and 35 respectively.Lewis acid-mediated deprotection of ester 33 provided (5R)-(Z)-6-(1-methyl-1,2,3-triazol-4-ylmethylene)penem-3-carboxylic acid 34 (BRL 42715) as a crystalline sodium salt monohydrate.The 6-heterocyclilmethylene penems, represented by BRL 42715, are potent inhibitors of bacterial β-lactamases and their combination with an appropriate penicillin or cephalosporin results in good synergistic activity against a broad range of β-lactamase-producing bacteria.

Microwave-Induced Organic Reaction Enhancement Chemistry. 2. Simplified Techniques

A variety of organic reactions have been conducted efficiently in a few minutes in unsealed vessels at ambient pressure in unmodified microwave ovens by using selected organic solvents.

BICYCLIC IMIDAZOLIDINONES AS POTENTIAL ANTIBIOTICS

The bicyclic imidazolidinones 5 topologically related to the penicillin family, are susceptible to form a stable carbamate with serine-D,D-peptidases.A series of N-7 acylated or sulfonylated (2R,5R)-3,3-dimethyl-8-oxo-4-thia-7,1-diazabicyclooctane-2-carboxylates 12-21 have been prepared.None of these novel penicillin analogs exhibited antibacterial activity.

EFFICIENT PREPARATION OF PENICILLANATE ESTER: A REDUCTIVE DEBROMINATION OF BROMOPENICILLANATE ESTER AND BROMOPENICILLANATE-S,S-DIOXIDE ESTER WITH TRI-N-BUTYLPHOSPHINE

Benzyl bromopenicillanate (5) and benzyl bromopenicillanate-S,S-dioxide (6) were subject to a reductive debromination in an effect of tri-n-butylphosphine furnishing benzyl penicillanate (7) and benzyl penicillanate-S,S-dioxide (8) in 50percent and 81percent yield respectively.

Process for 6-(aminomethyl)penicillanic acid 1,1-dioxide and derivatives thereof

A process for the preparation of beta-lactamase inhibiting 6-alpha-(aminomethyl)penicillanic acid 1,1-dioxide and derivatives. R- and S-1-(ethoxycarbonyloxy)ethyl 6-alpha-(aminomethyl)penicillanate 1,1-dioxide are specifically described.