78964-85-9

Basic information

• Product Name: Fosfomycin tromethamine
• Synonyms: (3-methyloxiranyl)-phosphonicaci(2r-cis)-phosphonicacicompd.with2-amino-2-(hydroxy;fosfomycincompd.withtrometamol;fosfomycintrometamolsalt;methyl)-1,3-propanediol(1:1);monuril;tromethamine-fosfomycin;z1282;FOSFOMYCIN TROMETAMOL
• CAS NO: 78964-85-9
• Molecular Formula: C₃H₇O₄P*C₄H₁₁NO₃
• Molecular Weight: 259.19
• EINECS: 279-018-8
• Product Categories: API;Antibiotics
• Mol File: 78964-85-9.mol
• Article Data: 5

Chemical Properties

• Boiling Point: 357 °C at 760 mmHg
• Flash Point: 169.7 °C
• Appearance: /
• Vapor Pressure: 1.57E-06mmHg at 25°C
• Storage Temp.: Hygroscopic, Refrigerator, under inert atmosphere
• Solubility: Very soluble in water, slightly soluble in ethanol (96 per cent) and in methanol, practically insoluble in acetone.
• Stability: Hygroscopic
• CAS DataBase Reference: Fosfomycin tromethamine(CAS DataBase Reference)
• NIST Chemistry Reference: Fosfomycin tromethamine(78964-85-9)
• EPA Substance Registry System: Fosfomycin tromethamine(78964-85-9)

Safety Data

• Hazardous Substances Data: 78964-85-9(Hazardous Substances Data)

Usage

Description

Fosfomycin tromethamine, also known as Monurol, is a phosphonic acid derivative that was initially isolated from fermentations of Streptomyces spp. It is a broad-spectrum, bactericidal antibacterial that inhibits the growth of various bacteria, including E. coli, S. aureus, and other species. The tromethamine salt form enhances its water solubility, allowing for oral administration. Fosfomycin covalently inactivates the first enzyme in the bacterial cell wall biosynthesis pathway, UDP-N-acetylglucosamine enolpyruvyl transferase (MurA), through alkylation of the cysteine-115 residue. It is available as a white to off-white powder and is marketed under the brand name Monurol by Zambon.

Uses

Used in Pharmaceutical Industry:
Fosfomycin tromethamine is used as an antibiotic compound for the treatment of urinary tract infections. It is particularly effective against E. coli, S. aureus, and other bacteria, with in vitro efficacy similar to that of norfloxacin and trimethoprim-sulfamethoxazole. Fosfomycin is recommended as single-dose therapy for uncomplicated urinary tract infections.
Additionally, fosfomycin has potential applications in other industries, such as:
Used in Research and Development:
Fosfomycin tromethamine can be used as a research tool to study the mechanisms of bacterial cell wall biosynthesis and the development of antibiotic resistance. This knowledge can contribute to the development of new antibacterial agents and strategies to combat drug-resistant infections.
Used in Veterinary Medicine:
Fosfomycin tromethamine may also be utilized in veterinary medicine for the treatment of bacterial infections in animals, similar to its application in human medicine. This can help in controlling bacterial infections in livestock and pets, ensuring their health and well-being.

InChI:InChI=1/C4H11NO3.C3H7O4P/c5-4(1-6,2-7)3-8;1-2-3(7-2)8(4,5)6/h6-8H,1-3,5H2;2-3H,1H3,(H2,4,5,6)/t;2-,3+/m.1/s1

Synthetic route

fosfomycin bis tromethamine → fosfomycin trometamol (78964-85-9)

Conditions	Yield
With acetic anhydride In methanol at 20 - 30℃; for 1.33333h;	95.1%

fosfomycin bis-tromethamine → fosfomycin trometamol (78964-85-9)

Conditions	Yield
Stage #1: fosfomycin bis-tromethamine In methanol at 20℃; for 0.25h; Stage #2: With Cyclohexyl isocyanate In methanol at 20℃; for 0.633333h; Reagent/catalyst;	90.5%

(1R,2S)-(-)-cis-1,2-epoxypropyl phosphoric acid-R-(+)-α-phenethylamine salt + 2-amino-2-hydroxymethyl-1,3-propanediol (77-86-1) → fosfomycin trometamol (78964-85-9)

Conditions	Yield
Stage #1: (1R,2S)-(-)-cis-1,2-epoxypropyl phosphoric acid-R-(+)-α-phenethylamine salt; 2-amino-2-hydroxymethyl-1,3-propanediol In methanol at 20℃; for 0.25h; Stage #2: With Cyclohexyl isocyanate In methanol at 20 - 33℃; for 0.633333h; Reagent/catalyst;	86.2%

C3H7O4P*C8H11N*C4H11NO3 → fosfomycin trometamol (78964-85-9)

Conditions	Yield
With methanesulfonic acid In ethanol at 48 - 50℃; for 0.833333h; Reagent/catalyst; Temperature;	72.3%
With methanesulfonic acid In ethanol at 48 - 50℃; for 0.833333h; Temperature;

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;

Upstream product

• 77-86-1 2-amino-2-hydroxymethyl-1,3-propanediol 
• 855392-18-6 2-amino-2-hydroxymethyl-propane-1,3-diol; hydrogenoxalate 
• 26016-99-9 phosphomycin disodium salt 

Relevant articles and documents

Preparing method of fosfomycin trometamol

The invention belongs to the technical field of medicinal chemistry, and particularly relates to a preparing method of fosfomycin trometamol. The method includes the following steps of firstly, addingfosfomycin diaminoglycol to methyl alcohol, dropwise adding acetic anhydride or propionic anhydride at a room temperature, and removing the methyl alcohol after a stirring reaction to obtain white solid; secondly, adding absolute ethyl alcohol to the obtained white solid, conducting cooling and filtering, conducting washing with ethyl alcohol, and conducting vacuum drying to obtain the fosfomycintrometamol. According to the preparing method, the acetic anhydride which is low in price and low in toxicity is adopted as the raw material, cost is low, three wastes are few, the environment protection pressure is small, the yield is high, operation is simple and convenient, and the method is suitable for industrial production; in the preparing method, no low-temperature ion exchange column isneeded, the fosfomycin diaminoglycol and acetic anhydride react at a room temperature, the reaction conditions are mild, and energy consumption is low.

Method for conveniently preparing fosfomycin trometamol

The invention discloses a synthesis method of fosfomycin trometamol. The method comprises the following steps: (1), taking fosfomycin phenylethylamine salt and tromethamine as raw material to preparefosfomycin bis (alpha-methylbenzylamine/tromethamine) salt, adding an alcoholic solution of methanesulfonic acid or para-toluenesulfonic acid in a stirring condition, stirring and performing cooling crystallization after dropwise adding is accomplished, and filtering to obtain a crude wet product; and (2), refining the crude product to obtain a refined product, and performing vacuum drying, so asto obtain a refined dried product. The method is simple to operate and mild in reaction condition, and ensures that both the product purity and the yield achieve high levels.

A process for the preparation of fosfomycin salts

A process for the preparation of fosfomycin trometamol, which comprises the reaction between fosfomycin disodium salt and a tromethamine acid salt with a carboxylic acid in a substantially anhydrous alcoholic solvent.