23155-02-4 Usage
Mode of action
The N-acetylmuramic acid component of the bacterial cell wall is derived from N-acetylglucosamine by the addition of a lactic acid substituent derived from phosphoenolpyruvate. Fosfomycin blocks this reaction by inhibiting the pyruvyl transferase enzyme involved. The antibiotic enters bacteria by utilizing active transport mechanisms for α-glycerophosphate and glucose-6-phosphate. Glucose-6-phosphate induces the hexose phosphate transport pathway in some organisms (notably Escherichia coli) and potentiates the activity of fosfomycin against these bacteria.
Chemical Properties
Water-soluble crystals.
Originator
Fosfocin,Crinos,Italy,1977
Uses
Antibacterial.
Definition
ChEBI: A phosphonic acid having an (R,S)-1,2-epoxypropyl group attached to phosphorus.
Manufacturing Process
(A) The preparation of [(1-chloroethoxy)chloromethyl]phosphonic acid:
Acetaldehyde (1.1 mol) and hydroxymethylphosphonic acid (1 mol) in 500 ml
of benzene are saturated with hydrogen chloride gas at 10°C to 15°C. The
mixture is aged at 25°C for 24 hr, the solvent distilled out in vacuo and the
residue flushed three times with benzene to remove all traces of hydrogen chloride. The residue is taken up in benzene (500 ml), treated with tert-butyl
hypochlorite (0.8 mol) and azobisisobutyronitrile (0.8 mm) at 40°C until
titration shows the absence of hypochlorite and the solution is then
evaporated to yield [(1-chloroethoxy)chloromethyl] phosphonic acid in the
form of an oil.
(B) The preparation of (cis-1,2-epoxypropyl)phosphonic acid: [(1-
chloroethoxy)chloromethyl] phosphonic acid (1.0 g) is added with stirring to
tetrahydrofuran (50 ml) to which has been added a crystal of iodine and a
zinc-copper couple (15.0 g). The mixture is then heated under reflux for 24 hr
and the resulting solution filtered to yield (cis-1,2-epoxypropyl)-phosphonic
acid.
There is also a fermentation route to Fosfomycin as noted by Kleeman and
Engel.
Therapeutic Function
Antibiotic
Clinical Use
Phosphomycin, introduced in 1972, inhibits enolpyruvial transferase, an enzyme catalyzing an early step in
bacterial cell wall biosynthesis. Inhibition results in reduced synthesis of peptidoglycan, an important
component in the bacterial cell wall. Phosphomycin is bactericidal against Escherichi a coli and Enterobacter
faecali s infections.
Drug interactions
Potentially hazardous interactions with other drugs
Metoclopramide: increases gastrointestinal motility
and therefore lowers the serum concentration and
urinary excretion of fosfomycin.
Metabolism
Fosfomycin undergoes no biotransformation and is
excreted mainly unchanged through the kidneys. This
results in very high urinary concentrations (up to 3
mg/mL) within 2-4 hours of a dose. Therapeutic
concentrations of 200-300 mcg/mL in urine are usually
maintained for at least 36 hours, and can last from 48-72
hours.
Check Digit Verification of cas no
The CAS Registry Mumber 23155-02-4 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 2,3,1,5 and 5 respectively; the second part has 2 digits, 0 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 23155-02:
(7*2)+(6*3)+(5*1)+(4*5)+(3*5)+(2*0)+(1*2)=74
74 % 10 = 4
So 23155-02-4 is a valid CAS Registry Number.
InChI:InChI=1/C3H7O4P/c1-2-3(7-2)8(4,5)6/h2-3H,1H3,(H2,4,5,6)/t2-,3+/m0/s1
23155-02-4Relevant articles and documents
Studies on the biosynthesis of fosfomycin. Conversion of 2-hydroxyethylphosphonic acid and 2-aminoethylphosphonic acid to fosfomycin
Imai,Seto,Ogawa,et al.
, p. 873 - 874 (1985)
-
A new non-chloride method of synthesis of antibacterial antibiotic fosfomycin based on the principles of green chemistry
Belakhov,Garabadzhiu
, p. 2974 - 2977 (2017/07/07)
A new non-chloride method for synthesis of antibacterial antibiotic fosfomycin, which is based on principles of green chemistry, has been developed.
Apparatus And Methods For Delivering A Plurality Of Medicaments For Management Of Co-Morbid Diseases, Illnesses Or Conditions
-
, (2010/09/07)
A method and apparatus for delivering a plurality of medicaments in a single delivery vehicle for the management of co-morbid diseases, illnesses and conditions. The present invention provides a novel delivery process for many medicaments. Medicaments may be encapsulated and stored separately within a larger capsule until the time of ingestion, consumption, or the like. Benefits of the present invention include maintaining separation of distinct ingredients within a single capsule and the capability to control the time release of multiple ingredients within the capsule.
Indirect evidence for the biosynthesis of (1S,2S)-epoxypropylphosphonic acid as a co-metabolite of fosfomycin [(1R,2S)-1,2-epoxypropylphosphonic acid] by Streptomyces fradiae
Simov, Biljana Peric,Wuggenig, Frank,Laemmerhofer, Michael,Lindner, Wolfgang,Zarbl, Elfriede,Hammerschmidt, Friedrich
, p. 1139 - 1142 (2007/10/03)
Treatment of the culture broth of fosfomycin (1) producing Streptomyces fradae with ammonia gives 2-3% of the C-1 epimeric compound 5, as well as the known (1R,2R)-2-amino-1-hydroxypropylphosphonic acid (3) derived from fosfomycin. The configuration of 5 was determined by capillary electrophoresis employing a quinine carbamate-type chiral selector and by synthesis from a monoprotected 1,2-dihydroxypropylphosphonate of known absolute configuration. It is postulated that (1S,2R)-2-amino-1-hydroxypropylphosphonic acid (5) is derived by ring opening of a trans-epoxide, formed as a co-metabolite of fosfomycin (cis-epoxide), with ammonia. Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002.