Clavulanic acid

Base Information

• Chemical Name: Clavulanic acid
• CAS No.: 58001-44-8
• Molecular Formula: C8H9NO5
• Molecular Weight: 199.163
• Hs Code.: 2934995000
• Mol file: 58001-44-8.mol

Synonyms:(Z)-(2R,5R)-3-(2-Hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo(3.2.0)heptane-2-carboxylic acid;Acide clavulanique;Acidum clavulanicum;Antibiotic MM 14151;BRL 14151;BRN 0787059;Clavulansaeure;MM 14151;UNII-23521W1S24;

Chemical Property of Clavulanic acid

Chemical Property:

• Appearance/Colour: Colorless needle-like crystal
• Vapor Pressure: 3.45E-14mmHg at 25°C
• Refractive Index: 1.644
• Boiling Point: 545.8 °C at 760 mmHg
• PKA: 3.68±0.20(Predicted)
• Flash Point: 283.9 °C
• PSA: 87.07000
• Density: 1.65 g/cm³
• LogP: -1.15770

Purity/Quality:

98%,99%, ^*data from raw suppliers

Clavulanic acid ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Description: Clavulanic acid is a mold product with only weak intrinsic antibacterial activity, but it is an excellent irreversible inhibitor of most β-lactamases. It is believed to acylate the active site serine by mimicking the normal substrate. Hydrolysis occurs with some β-lactamases, but in many cases, subsequent reactions occur that inhibit the enzyme irreversibly. This leads to its classification as a mechanism-based inhibitor (or so-called suicide substrate). The precise chemistry is not well understood, but when clavulanic acid is added to ampicillin and amoxicillin preparations, the potency against β-lactamase–producing strains is markedly enhanced.
• Uses: beta-lactamase inhibitor
• Therapeutic Function: Antibacterial
• Clinical Use: Clavulanic acid is an antibiotic isolated from Streptomycesclavuligeris. Structurally, it is a 1-oxopenam lacking the6-acylamino side chain of penicillins but possessing a 2-hydroxyethylidene moiety at C-2. Clavulanic acid exhibitsvery weak antibacterial activity, comparable with that of6-APA and, therefore, is not useful as an antibiotic. Itis, however, a potent inhibitor of S. aureus β-lactamaseand plasmid-mediated β-lactamases elaborated by Gramnegativebacilli.Combinations of amoxicillin and the potassium saltof clavulanic acid are available (Augmentin) in variousfixed-dose oral dosage forms intended for the treatment ofskin, respiratory, ear, and urinary tract infections causedby -lactamase–producing bacterial strains. These combinationsare effective against β-lactamase–producingstrains of S. aureus, E. coli, K. pneumoniae, Enterobacter,H. influenzae, Moraxella catarrhalis, and Haemophilusducreyi, which are resistant to amoxicillin alone. The oral bioavailability of amoxicillin and potassium clavulanate issimilar. Clavulanic acid is acid-stable. It cannot undergo penicillanicacid formation because it lacks an amide side chain.Potassium clavulanate and the extended-spectrum penicillinticarcillin have been combined in a fixed-dose, injectableform for the control of serious infections caused byβ-lactamase–producing bacterial strains. This combinationhas been recommended for septicemia, lower respiratory tractinfections, and urinary tract infections caused by β-lactamase–producing Klebsiella spp., E. coli, P. aeruginosa,and other Pseudomonas spp., Citrobacter spp., Enterobacterspp., S. marcescens, and S. aureus. It also is used in bone andjoint infections caused by these organisms. The combinationcontains 3 g of ticarcillin disodium and 100 mg of potassiumclavulanate in a sterile powder for injection (Timentin).

Technology Process of Clavulanic acid

There total 10 articles about Clavulanic acid which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 84.0%

Benzyl Clavulanate (57943-84-7) → clavulanic acid (58001-44-8)

Guidance literature:

With hydrogen; palladium on activated charcoal; In ethanol; for 0.75h; under 760 Torr; Ambient temperature;

Reference yield: 73.0%

→ Clavulanic acid 2-amino-2-methylpropane salt + clavulanic acid (58001-44-8)

Guidance literature:

Reference yield:

methyl clavulanate (57943-82-5) → clavulanic acid (58001-44-8)

Guidance literature:

Multi-step reaction with 3 steps

1: 70 percent / sodium hydroxide / H₂O / 1.17 h / 0 °C

2: 69 percent / dimethylformamide / 1.5 h / Ambient temperature

3: 84 percent / H₂ / palladium on carbon / ethanol / 0.75 h / 760 Torr / Ambient temperature

With sodium hydroxide; hydrogen; palladium on activated charcoal; In ethanol; water; N,N-dimethyl-formamide;

upstream raw materials:

(5RS)-<5-(3)H>-L-ornithine

Benzyl Clavulanate

Ornithin-dihydrochlorid

methyl clavulanate

Downstream raw materials:

methyl clavulanate

1-benzyloxycarbonylamino-4-hydroxybutan-2-one

(Z)-(3S,5R)-2-(2-hydroxyethylidene)-3-(m-chlorobenzoyloxy)clavam

N-benzylclavulanamide

Refernces

Preparation of 2-exomethylene penam and penicillin-2-carboxylate systems

10.1039/c39870000081

The research details the preparation of penicillin-2-carboxylate systems and their conversion into 2-methylene penam and 2-methyl penem systems through a decarboxylative Pummerer reaction. The purpose of this study was to synthesize the 2-exomethylene penam system, which serves as a structural bridge between penicillin and clavulanic acid, and was previously unknown. The researchers successfully synthesized this system and demonstrated its conversion to other penicillin derivatives. Key chemicals used in the process included penicillin V, various oxidants, dimethyl sulphoxide (DMSO), oxalyl chloride, pyridine, 2,6-lutidine, molecular sieves, and phosphorus tribromide in dimethylformamide (DMF). The conclusions drawn from the study indicated that the synthesized compounds, including the 2-exomethylene penam system and the dicarboxylate (12), showed comparable antibacterial activity to penicillin V, while the amide (21) exhibited an order of magnitude lower in activity.

A FACILE SYNTHESIS OF BENZYL 3,7-DIOXO-1-AZABICYCLO<3.2.0>HEPTANE-2-CARBOXYLATE. A POTENTIAL PRECURSOR OF THIENAMYCIN AND CLAVULANIC ACID ANALOGS

10.1016/S0040-4039(01)81957-2

The study presents a novel, high-yield synthesis of the 1-carbapenam ring system, a precursor to thienamycin and clavulanic acid analogs. The entire carbon framework is introduced in a single step from simple precursors. Benzyl sorbate is isomerized to 3,5-hexadienoate, which reacts with chlorosulfonyl isocyanate to form B-lactam. This compound is then converted to an iodo-hydrin, reduced to an alcohol, and oxidized to a ketoester. The ketoester undergoes diazo group transfer and rhodium-catalyzed ring closure to form the final product. The study also explores the synthesis of o-nitrobenzyl ester derivatives and attempts to convert these compounds to the corresponding acids, though these attempts were unsuccessful due to decomposition. The synthesized compounds are analyzed using various techniques, including IR, NMR, and mass spectrometry.