26016-99-9

Basic information

• Product Name: Disodium phosphonomycin
• Synonyms: [(2R,3S)-3-Methyloxiran-2-yl]phosphonic acid disodium salt;Fosfomycin sodium;disodium [(2R,3S)-3-methyloxiran-2-yl]-bis(oxidanidyl)-oxo-$l^{5}-phosphane;disodium [(2R,3S)-3-methyloxiran-2-yl]-dioxido-oxo-$l^{5}-phosphane;disodium keto-[(2R,3S)-3-methyloxiran-2-yl]-dioxido-phosphorane;Sodium ((2S,3R)-3-methyloxiran-2-yl)phosphonate;2S)-1;(1,2-epoxypropyl)-,disodiumsalt(1r,2s)(-)-phosphonicaci
• CAS NO: 26016-99-9
• Molecular Formula: C₃H₅O₄P*2Na
• Molecular Weight: 182.02
• EINECS: 247-409-2
• Product Categories: API;antibiotic;Antibiotics;chiral;Antibiotic Explorer;Intermediates & Fine Chemicals;Pharmaceuticals;Peptide Synthesis/Antibiotics
• Mol File: 26016-99-9.mol

Chemical Properties

• Melting Point: >300°C
• Boiling Point: 342.7oC at 760 mmHg
• Flash Point: 161°C
• Appearance: white solid
• Vapor Pressure: 1.34E-05mmHg at 25°C
• Storage Temp.: 2-8°C
• Solubility: H2O: 50 mg/mL, clear, colorless
• Water Solubility: Freely soluble in water or aqueous solution
• BRN: 4604425
• CAS DataBase Reference: Disodium phosphonomycin(CAS DataBase Reference)
• NIST Chemistry Reference: Disodium phosphonomycin(26016-99-9)
• EPA Substance Registry System: Disodium phosphonomycin(26016-99-9)

Safety Data

• Hazard Codes: F,C
• Statements: 11-34
• Safety Statements: 16-26-36/37/39-45
• WGK Germany: 2
• RTECS: SZ7902000
• F: 10-21
• Hazardous Substances Data: 26016-99-9(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Disodium phosphonomycin is used as an antibiotic for the treatment of infections caused by Staphylococcus aureus, Escherichia coli, Proteus, and Shigella. It is effective in treating uncomplicated urinary tract infections and reducing nephrotoxicity and ototoxicity of platinum-containing anti-tumor agents.
Used in Medical Research:
Disodium phosphonomycin is used for susceptibility studies of Klebsiella pneumoniae and to study in vitro susceptibility testing procedures for fosfomycin tromethamine. This helps in understanding the effectiveness of the antibiotic against different bacterial strains and contributes to the development of new treatments.
Used in Curariform Muscle Relaxants:
Disodium phosphonomycin is used as a curariform muscle relaxant, which helps in inducing muscle paralysis during surgical procedures. This allows for better control and precision during surgeries, improving patient outcomes.
Used in Inhibiting Bacterial Cell Wall Synthesis:
Disodium phosphonomycin is used as an inhibitor of MurA, an enzyme responsible for synthesizing N-acetylmuramic acid or NAM, a major component of peptidoglycan. By preventing peptidoglycan synthesis, it effectively inhibits bacterial cell wall formation, leading to the death of the bacteria.

Appearance Properties

It appears as a white crystalline powder at room temperature, hygroscopic, easily soluble in water, heated while dissolving. Fosfomycin Sodium can combine with a bacterial cell wall synthesis enzyme, hinder bacterial cell wall synthesis related substances utilizing at the first reaction, which in turn has a bactericidal effect. have antibacterial effect for Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Neisseria gonorrhoeae, Proteus mirabilis, Salmonella typhi, Serratia bacteria, most Pseudomonas aeruginosa, Streptococcus pyogenes, Streptococcus faecalis, part indole-positive Proteus and certain Klebsiella, Enterobacter bacteria. The main clinical applications of Fosfomycin Sodium include: urinary tract treatment of sensitive Gram-negative bacteria caused urinary system, infection of skin and soft tissue, respiratory, intestinal and other parts. It can also be combined with other antibiotics, the treatment of severe infections caused by susceptible strains such as sepsis, pulmonary, meningeal infections, peritonitis, adnexitis, intrauterine infections, pelvic inflammatory disease, osteomyelitis. Also in combination with vancomycin for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infection.

Pharmacological effects

1. Broad spectrum antibiotic, high bioavailability, rapid absorption, strong anti-bacterial, not diet affected. Fosfomycin Sodium displays effects on killing Gram-positive and Gram-negative bacteria, especially Pseudomonas aeruginosa, Proteus, Salmonella, and exhibit excellent antibacterial activity for a variety of drug-resistant Staphylococcus aureus and Escherichia coli. For usage in animals, there is no drug resistance and cross-resistance. Clinical effect is good. 2. Rapid sterilization: This product is a rapid fungicide, its role is still evident after 1-2 hours. About 25% of the E. coli were killed at 1 hour after exposured to Fosfomycin Sodium (12.5μg/ml), and all died within 4-6 hours. Pseudomonas aeruginosa and Staphylococcus aureus were also all killed at 4 and 8 hours. 3. Low toxicity, little irritation on the body, no acute toxicity and adverse reactions, no increased burden on the kidney. 4. Low residue: the eliminate time for the muscles and organs to reach the residual standard is 48-72 hours. The above information is edited by the lookchem of Tian Ye.

Indications

Mainly used for Staphylococcus aureus, streptococcus, E. coli, Salmonella and other gram-negative bacteria caused acute and chronic bowel disease treatment in chickens, ducks, pigs.

Usage and dosage

Used in water for livestock and poultry: every 100kg of water added the product 5-10 grams, 2 times a day, once every three days. Used in animal spices: 10-15 g of the product added to per 100kg feed, 2 times a day, once every three days.

Combination therapy

For the treatment of intestinal infections, Fosfomycin Sodium can combine with β-lactam, aminoglycoside. For the treatment of respiratory and lung infections, combining with macrolides, β-lactam. For staph infections, better combined with erythromycin, rifampin. For the treatment of acute respiratory infections, sepsis, peritonitis ect., increase the dose. Need to combine with β-lactams or aminoglycosides.

Detection Indicator

No. Test item Export standard CP2000 Edition 1 Traits: A white crystalline powder, odorless, taste salty white crystalline powder, odorless, salty taste 2 Discriminator: Positive reaction Positive reaction 3 Specific rotation °-4.2 ~-5.5-4.2 ~-5.5 4 Heavy Metal ≤0.0010% 0≤.0010% 5 Content ≥700μ/mg ≥700μ/mg 6 Alkalinity 9.0-10.5 9.0-10.5 7 Weight loss on drying ≤1.0% ≤1.5% (water) 8 Solution clarity ≤No. 3/4 turbidity standards solution ≤No. 1 turbidity standard solution 9 Color of the solution ≤Yellow No. 1 ≤ Yellow No. 1 10 Glycols ≤0.50% ≤0.50% 11 Clarity of solution: can not be detected, in compliance with (a gross point ≤8/g, wherein a color point ≤2/g) 12 W ≤0.002%- 13 phosphorus content-16.2-17.9% 14 Sterile: Subject to compliance 15 Heat source/ bacterial endotoxin: compliance (heat source) compliance (bacterial endotoxin) 16 α-phenylethylamine ≤0.01%- 17 Residual amount of methanol: real 18 Residual amount of ethanol: Real The above information is the main export detection index of fosfomycin.

Precautions

1. This product is mainly used for pigs, chickens, fish; application for other animals should medication under veterinary guidance. 2. Fosfomycin Sodiumand β-lactams, aminoglycosides, macrocyclic acid esters have a synergistic effect of combination therapy, and can reduce or delay the occurrence of bacterial resistance.

InChI:InChI=1/C3H7O4P.2Na/c1-2-3(7-2)8(4,5)6;;/h2-3H,1H3,(H2,4,5,6);;/q;2*+1/p-2/t2-,3+;;/m0../s1

Synthetic route

syn-(1R,2S)-1-chloro-2-hydroxypropane phosphonic acid disodium salt → phosphomycin disodium salt (26016-99-9)

Conditions	Yield
With sodium hydroxide for 1h;	90%

dibenzyl (1R,2S)-1,2-epoxypropylphosphonate (172585-28-3) → phosphomycin disodium salt (26016-99-9)

Conditions	Yield
With Dowex 50WX8 (Na form); hydrogen; cyclohexylamine; palladium on activated charcoal In methanol	76%

(1-bromo-2-hydroxypropyl)phosphonic acid (119007-50-0) → phosphomycin disodium salt (26016-99-9)

Conditions	Yield
With sodium methylate In methanol	1.91 g

(1R,2S)-1-chloro-2-hydroxypropanephosphonic acid (640716-21-8) → phosphomycin disodium salt (26016-99-9)

Conditions	Yield
With sodium hydroxide In methanol pH=9 - 10;

disodium (1S,2S)-2-hydroxy-1-methanesulphonyloxypropyl phosphonate → phosphomycin disodium salt (26016-99-9)

Conditions	Yield
With sodium hydroxide In water
With sodium hydroxide In water
With sodium hydroxide In water

phosphomycin disodium salt (26016-99-9) + cyclohexylamine (108-91-8) → ((1R,2R)-1,2-Dihydroxy-propyl)-phosphonic acid; compound with cyclohexylamine (132125-61-2)

Conditions	Yield
With sulfuric acid at 50℃; for 48h;	60%

phosphomycin disodium salt (26016-99-9) → (1S,2S)-(+)-(1-Amino-2-hydroxypropyl)phosphonsaeure (128708-51-0) + (1R,2R)-(-)-(2-Amino-1-hydroxypropyl)phosphonsaeure (84601-12-7)

Conditions	Yield
With ammonia at 60℃;	A 42% B 58%

2-amino-2-hydroxymethyl-propane-1,3-diol; hydrogenoxalate (855392-18-6) + phosphomycin disodium salt (26016-99-9) → fosfomycin trometamol (78964-85-9)

Conditions	Yield
In methanol at 20 - 65℃; for 3 - 4h;

dimethyltin dichloride (753-73-1) + phosphomycin disodium salt (26016-99-9) → Me2Sn((1R,2S)-1,2-epoxypropylphosphonate)

Conditions	Yield
In methanol 1:1 mixt. stirred for 24 h at 40°C; pptd. on cooling, septd., recrystd. (benzene/chloroform=1/1), dried overP4O10 (vac.), elem. anal.;

trimethyltin(IV)chloride (1066-45-1) + phosphomycin disodium salt (26016-99-9) → (Me3Sn)2((1R,2S)-1,2-epoxypropylphosphonate)

Conditions	Yield
In methanol stoich. mixt. stirred for 24 h at 40°C; pptd. on cooling, septd., recrystd. (benzene/chloroform=1/1), dried overP4O10 (vac.), elem. anal.;

dibutyltin chloride (683-18-1) + phosphomycin disodium salt (26016-99-9) → Bu2Sn((1R,2S)-1,2-epoxypropylphosphonate)

Conditions	Yield
In methanol 1:1 mixt. stirred for 24 h at 40°C; pptd. on cooling, septd., recrystd. (benzene/chloroform=1/1), dried overP4O10 (vac.), elem. anal.;

phosphomycin disodium salt (26016-99-9) + triphenyltin chloride (639-58-7) → (Ph3Sn)2((1R,2S)-1,2-epoxypropylphosphonate)

Conditions	Yield
In methanol stoich. mixt. stirred for 24 h at 40°C; pptd. on cooling, septd., recrystd. (benzene/chloroform=1/1), dried overP4O10 (vac.), elem. anal.;

phosphomycin disodium salt (26016-99-9) → fosfomycin (23155-02-4)

Conditions	Yield
With Dowex 50x8, H(+) In water

phosphomycin disodium salt (26016-99-9) → (1R,2R) (1,2-dihydroxypropyl)phosphonate + (1S,2S) (1,2-dihydroxypropyl)phosphonate

Conditions	Yield
With water; sodium hydroxide at 90℃; for 24h;

Upstream product

• 640716-21-8 (1R,2S)-1-chloro-2-hydroxypropanephosphonic acid 
• 172585-28-3 dibenzyl (1R,2S)-1,2-epoxypropylphosphonate 
• 119007-50-0 (1-bromo-2-hydroxypropyl)phosphonic acid 

Downstream Products

• 23155-02-4 fosfomycin 
• 78964-85-9 fosfomycin trometamol 
• 132125-61-2 ((1R,2R)-1,2-Dihydroxy-propyl)-phosphonic acid; compound with cyclohexylamine 

Relevant articles and documents

Asymmetric synthesis of (-)-fosfomycin and its trans-(1S,2S)-diastereomer using a biocatalytic reduction as the key step

Fosfomycin is a gram positive and gram negative antibiotic that contains an asymmetric epoxide. An enzyme library was screened for its ability to reduce dimethyl(1-chloro-2-oxopropyl)phosphonate to the corresponding asymmetric chlorohydrin. Homology models were built in MOE, which were shown to accurately model the enzyme-substrate complex displaying the stereoselectivity that we observed. Two enzymes, YDR368w and YHR104w, were chosen for the scale up and synthesis of fosfomycin and its trans-(1S,2S)-diastereomer.

Enzymatic synthesis of phosphocarnitine, phosphogabob and fosfomycin

Phosphocarnitine was conveniently obtained from easily available diethyl 3-chloro-2-oxopropanephosphonates, followed by subsequent reduction, Mucor miehei lipase (IM) mediated resolution, amination and dealkylation. Candida antarctica lipase B (CALB) serv

Silicon Directed Asymmetric Synthesis of (1R,2S)-(-)-(1,2-Epoxypropyl)phosphonic Acid (Fosfomycin) from (S)-Lactaldehyde

The title compound is obtained in high diastereomeric purity based on the stereoselective addition of trimethylsilyldibenzylphosphite (TMSDBP) to O-triisopropylsilyloxy (S)-lactaldehyde.

Process for the preparation of intermediates for the synthesis of fosfomycin

A process is described for the preparation of intermediates useful in the synthesis of Fosfomycin. More particularly, an enantioselective process is described for the preparation of derivatives of (1S,2S)-1,2-dihydroxypropyl-phosphonic acid of formula STR1 wherein R2 and R3 have the meanings reported in the specification.

Process for the preparation of intermediates for the synthesis of fosfomycin

A process is described for the preparation of intermediates useful in the synthesis of Fosfomycin. More particularly, an enantioselective process is described for the preparation of derivatives of (1S,2S)-1,2-dihydroxypropyl--phosphonic acid of formula wherein R2 and R3 have the meanings reported in the specification.

Process for the preparation of antibiotics

Intermediate compounds of formula wherein R and R1 are the same or different and each represents a lower alkoxy or a -N(R2)2 group and both R2, independently, represent a hydrogen atom or a lower alkyl; the carbon atoms marked by an asterisk are both in R or S configuration;, allow to obtain enantioselectively the antibiotic known as Fosfomycin by an epoxidation reaction, carried out in the one or two steps, and a hydrolysis reaction.