CARBENICILLIN Chemical Properties

Boiling point:

737.8±60.0 °C(Predicted)

Density 

1.53±0.1 g/cm3(Predicted)

storage temp. 

−20°C

solubility 

Soluble in DMSO

form 

Powder

pka

pKa 2.22±0.05(H2O t = 25.0 I = 0.15 (KCl)) (Uncertain);3.25±0.02 (Uncertain)

CAS DataBase Reference

4697-36-3

Safety Information

Hazard Codes 

Xn

Risk Statements 

10-42/43

Safety Statements 

36/37-45-22

RIDADR 

UN 1170 3/PG 3

WGK Germany 

2

Hazardous Substances Data

4697-36-3(Hazardous Substances Data)

MSDS

• Language:English Provider:SigmaAldrich

CARBENICILLIN Usage And Synthesis

Brand Name(s) in US

Carbenicillin: Geopen, Pyopen
Carbenicillin indanyl sodium: Geocillin

Originator

Pyopen,Beecham,Switz.,1968

Uses

Antibacterial.

Definition

ChEBI: A penicillin antibiotic having a 6beta-2-carboxy-2-phenylacetamido side-chain.

Indications

Carbenicillin has a broad spectrum of antibacterial use with respect to Gram-negative and Gram-positive microorganisms. However, using this drug for infections caused by Grampositive microorganisms is pointless. It is used for diseases such as urinary tract infections, septicemia, endocarditis, meningitis, osteomelitis, peritonitis, purulent otitis, infected wounds, infected burns, and so on that are caused by Gram-negative microorganisms which are sensitive to such antibiotics. Synonyms of this drug are carindapen, pyopen, geopen, gripenin, and others.

Manufacturing Process

The required monobenzyl phenylmalonate, MP 68°C, was prepared by treating a mixture of phenylmalonic acid (18 g) and benzyl alcohol (13 g) in carbon tetrachloride (80 ml) with dry hydrogen chloride.
Monobenzyl phenylmalonate (13.3 g) in dry benzene (100 ml) was refluxed with thionyl chloride (6.45 g) for 90 minutes, then concentrated in vacuo. The residual oil was dissolved in dry acetone (50 ml) and added to a stirred, ice-cooled solution of 6-aminopenicillanic acid (9.7 g) in N sodium bicarbonate solution (135 ml), water (150 ml), and acetone (300 ml). The mixture was stirred for 30 minutes at 0°C and then for 90 minutes at room temperature, then concentrated under reduced pressure to remove acetone. The aqueous solution was brought to pH 2 with dilute hydrochloric acid and extracted with ether (3 x 100 ml). The ether solution was washed with water and then itself extracted with sufficient N sodium bicarbonate solution to give an aqueous phase of pH 7.5. The aqueous layer was separated and evaporated at low temperature and pressure to leave the impure sodium salt of alpha- (benzyloxycarbonyl) benzylpenicillin.
This crude product (15.8 g) in water (360 ml) was added to a prehydrogenated suspension of 10% palladium on charcoal (4 g) in water (400 ml), and hydrogenation was continued for 30 minutes. The catalyst was removed and the filtrate was adjusted to pH 7.5 with sodium bicarbonate, then evaporated at low temperature and pressure. The residue was purified by chromatography on a column of cellulose powder, eluting first with butanol/ethanol/water mixture and then with acetone/isopropanol/water. The main fraction was evaporated at low temperature and pressure to give a 32% yield of the sodium salt of alpha-carboxybenzylpenicillin as a white powder. The product was estimated by monometric assay with penicillinase to be 58% pure.

brand name

Geopen (Roerig); Pyopen (GlaxoSmithKline).

Therapeutic Function

Antibacterial

Antimicrobial activity

α-Carboxybenzylpenicillin; the first antipseudomonal penicillin to be developed. A semisynthetic carboxypenicillin supplied as the disodium salt for parenteral administration. The two esterified prodrug formulations, carindacillin (carbenicillin indanyl sodium) and carfecillin (carbenicillin carboxyphenyl ester) are no longer available.
It is the least active of the group 5 agents, even against Ps. aeruginosa (MIC 64 mg/L) with notably reduced activity against Gram-positive cocci. It is labile to many plasmidmediated β-lactamases, but is comparatively stable to class C chromosomal β-lactamases (pp. 228–230). Synergy is demonstrable with aminoglycosides against Ps. aeruginosa and other Gram-negative bacteria.
It is not orally absorbed, except in esterified form. A 1 g intramuscular injection achieves a plasma peak concentration of 20–30 mg/L after 0.5–1.5 h. The half-life is around 1 h. Plasma protein binding is 50–60%.
The drug is distributed in the extracellular fluid, providing concentrations up to 60% of those of the plasma. In patients with cystic fibrosis sputum concentrations may not reach inhibitory levels for Ps. aeruginosa. It does not cross the normal meninges but levels of up to 50% of those of the plasma can be found in patients with meningitis. Around 80% of the dose appears as unchanged drug in the urine, producing very high levels (2–4 g/L). It is more rapidly disposed of in patients with cystic fibrosis. Hypersensitivity reactions may occur, but these are less frequent and severe than those associated with benzylpenicillin. High blood levels sometimes cause a coagulation defect that has occasionally progressed to life-threatening bleeding in patients with impaired excretion while receiving 500 mg/kg per day or more. Reversible abnormalities of liver function apparently occur more commonly than with other antipseudomonal penicillins. Since large doses of the drug have to be used, convulsions can occur (as with other penicillins; p. 203) and, being administered as the disodium salt, electrolyte disturbances can result. It was formerly used for treatment of serious infections, especially those involving Ps. aeruginosa. It has extremely limited availability.

Biological Activity

carbenicillin is broad-spectrum semisynthetic penicillin derivative used parenterally.

Synthesis

Carbenicillin, [2S-(2|á,5|á,6|?)]-3,3-dimethyl-7-oxo-6-(2-carboxy-2- phenylacetamido)-4-thia-1-azabicyclo[3.2.0]-heptan-2-carboxylic acid (32.1.1.32), is synthesized by direct acylation of 6-APA in the presence of sodium bicarbonate by phenylmalonic acid monobenzyl ester chloride, which forms the benzyl ester of carbenicillin (32.1.1.31), the hydrogenolysis of which using palladium on carbon or calcium carbonate as catalyst gives the desired product (32.1.1.32).

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