34444-01-4 Usage
Description
7-[(2-Hydroxy-2-phenylacetyl)amino]-3-[(1-methyltetrazol-5-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid is a complex organic compound with a unique chemical structure. It is characterized by its molecular formula and various functional groups, which contribute to its potential applications in different industries.
Uses
Used in Pharmaceutical Industry:
7-[(2-Hydroxy-2-phenylacetyl)amino]-3-[(1-methyltetrazol-5-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid is used as an intermediate for the preparation of Phenylephrine Glucuronide, a medication with potential applications in treating conditions such as hypotension and nasal congestion.
Used in Antibacterial Applications:
In the pharmaceutical industry, 7-[(2-Hydroxy-2-phenylacetyl)amino]-3-[(1-methyltetrazol-5-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid is also used in the development of Cefamandole, a second-generation cephalosporin antibiotic with potent antibacterial activity. Cefamandole is effective against a wide range of bacterial infections and has similar pharmacological actions to other cephalosporin antibiotics like cefuroxime and cefamandole.
Used in Chemical Synthesis:
7-[(2-Hydroxy-2-phenylacetyl)amino]-3-[(1-methyltetrazol-5-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, due to its unique chemical structure, can be utilized as a key intermediate in the synthesis of various other complex organic compounds, potentially leading to the development of new drugs and materials.
Chemical Properties:
7-[(2-Hydroxy-2-phenylacetyl)amino]-3-[(1-methyltetrazol-5-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid is characterized by its off-white foam appearance, which may be indicative of its physical properties and potential applications in various industries.
Brand Name:
Under the brand name Mandol (Lilly), 7-[(2-Hydroxy-2-phenylacetyl)amino]-3-[(1-methyltetrazol-5-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid may be marketed and distributed for its pharmaceutical applications.
Originator
Mandokef,Lilly,W. Germany,1977
Manufacturing Process
To 21.6 kg (17.8 l) of 98% formic acid was added 1.14 kg (7.5 mols) of D-(-)-
mandelic acid and the reaction mixture was heated for 4 hours at 70°C with
stirring. The excess formic acid was evaporated off in vacuo and the residual
syrup was dissolved in 6 l of benzene. The solution was washed twice with 6 l
portions of water and was dried over magnesium sulfate. The drying agent
was filtered and washed with 1.5 l of benzene, the washes being added to the
filtrate. The dried filtrate was evaporated in vacuo to obtain the D-(-)-
mandelic acid formate ether as a syrup. The product can be crystallized from
cyclohexane to yield material melting at about 55°C to 58°C.The mandelic acid formate ester obtained as a syrup as described above is
stirred for 2 hours with 2.9 kg (~1.75 l) of thionyl chloride at a temperature
of about 70°C. The excess thionyl chloride is removed by evaporation and the
residual green solution is vacuum distilled. The product, O-formyl mandeloyl
chloride, distills over at 127°C to 130°C (15 mm) or at 108°C to 112°C (7
mm).To 13 l of ethyl acetate were added 85.1 g (2.59 mols) of 7-amino-3-(1-
methyl-1H-tetrazol-5-ylthiomethyl)-3-cephem-4-carboxylic acid and 1,361 g
(10.37 mols) of monotrimethylsilyl acetamide, and the mixture was stirred at
50°C until a clear solution was obtained. The solution was cooled to 20°C and
514 g (2.59 mold of O-formyl mandeloyl chloride was added at a rate such
that the temperature of the reaction solution was maintained between about
20°C to 25% with ice-cooling.The reaction mixture was stirred for 1.5 hours at about room temperature
after the addition of the mandeloyl chloride was completed. Five liters of
water were then added to the reaction mixture and the diluted mixture was
stirred for about 10 minutes. The organic layer was separated and was
washed twice with water. The combined washes are extracted with 1.5 l of
ethyl acetate and the extract is combined with the washed organic layer. The
whole was dried over magnesium sulfate, filtered and evaporated in vacuo on
a 25°C water bath to yield 1,460 g of product, 7-(D-2-formyloxy-2-
phenylacetamido)-3-(1-methyl-1H-tetrazol-5-ylthiomethyl)-3-cephem-4-
carboxylic acid, as a yellow foam.The product was dissolved in 5 l of acetone and the solution was mixed with a
solution of 430 g (2.59 mols) of sodium 2-ethylhexanoate in 5.4 l of acetone.
The combined solutions were seeded and stirred in an ice bath for 1.5 hours.
The crystalline precipitate of sodium 7-(D-2-formyloxy-2-phenylacetamido)-3-
(1-methyl-1H-tetrazol-5-ylthiomethyl)-3-cephem-4-carboxylate was filtered
and washed with 5 l of acetone. The crystalline salt was dried overnight in a
vacuum oven at 40°C to yield 1,060 g (80%)of product, melting at 182°C to
184°C.
Therapeutic Function
Antibiotic
Antimicrobial activity
A semisynthetic cephalosporin supplied as the nafate, an
antibacterially inactive ester hydrolyzed in the body to cefamandole.
It is active against common pathogenic bacteria
, but there is considerable strain variation in
susceptibility. It is somewhat more stable than other group 1
agents to enterobacterial β-lactamases. Acinetobacter,
Serratia and Pseudomonas spp. are often resistant. Some
anaerobic Gram-negative rods are susceptible but B. fragilis
is resistant.
A 1 g intramuscular dose achieves a plasma concentration
of 20–35 mg/L after 1 h. It is widely distributed in body tissues.
CSF levels are poor in the absence of meningeal inflammation.
Therapeutically effective concentrations (c. 9 mg/kg)
are found in bone after an intravenous dose of 2 g. Protein
binding is 65–80%.
Renal excretion with a plasma half-life of around
50 min is mainly by both glomerular and tubular routes.
A small amount is excreted in the bile and concentrations
around 150–250 mg/L are found in T-tube bile following
a 1 g intravenous dose. Only about 5% is removed by
hemodialysis.
Cefamandole is one of the analogs containing the methylthiotetrazole
side chain associated with bleeding .
Rare renal damage or enhancement of existing renal damage
has been described. Thrombophlebitis on intravenous administration
is relatively common.
Experience in the treatment of a variety of infections and
for surgical prophylaxis has been mixed and it is no longer
recommended.
Synthesis
Cefamandole, 7-D-mandelamido-3-[[(1-methyl-1H-tetrazol-5-yl)thio]
methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-2-carboxylic acid (32.1.2.25), is synthesized from 7-aminocephalosporanic acid.
Protecting free amino group in 7-aminocephalosporanic acid by formylation with formic
acid in the presence of acetic anhydride produces 7-formamidocephalosporanic acid
(32.1.2.23). The acetoxy group of this compound is replaced by a reaction with 1-methyl-
1,2,3,4-tetrazol-5-thiol, after which the N-formyl protection is removed by hydrochloric
acid, giving 7-amino-3-(1-methyl-1,2,3,4-tetrazol-5-yl)-thiomethyl-3-cefem-4-carboxylic
acid (32.1.2.24). Reacting this with a mixed anhydride synthesized from mandelic acid and
phosgene gives the desired cefamandole (32.1.2.25).
Check Digit Verification of cas no
The CAS Registry Mumber 34444-01-4 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 3,4,4,4 and 4 respectively; the second part has 2 digits, 0 and 1 respectively.
Calculate Digit Verification of CAS Registry Number 34444-01:
(7*3)+(6*4)+(5*4)+(4*4)+(3*4)+(2*0)+(1*1)=94
94 % 10 = 4
So 34444-01-4 is a valid CAS Registry Number.
InChI:InChI=1/C19H18N6O6S2.Na/c1-24-19(21-22-23-24)33-8-11-7-32-17-12(16(28)25(17)13(11)18(29)30)20-15(27)14(31-9-26)10-5-3-2-4-6-10;/h2-6,9,12,14,17H,7-8H2,1H3,(H,20,27)(H,29,30);/q;+1/p-1
34444-01-4Relevant articles and documents
PROCESS FOR THE PREPARATION OF CEFAMANDOLE NAFATE
-
Page/Page column 9, (2013/05/09)
The present invention relates to a process for the preparation of cefamandole nafate from cefamandole and to the use thereof in the manufacture of a medicament for treatment of a bacterial disease.
Coupling of Site-Directed mutagenesis and immobilization for the rational design of more efficient biocatalysts: The case of immobilized 3G3K PGA from E. coli
Serra, Immacolata,Ceechini, Davide A.,UbiaIi, Daniela,Manazza, Elena M.,Albertini, Alessandra M.,Terreni, Marco
experimental part, p. 1384 - 1389 (2009/08/07)
We have investigated the synthetic performance of the immobilized 3G3K mutant of the Penicillin G acylase (PGA) from E. coli obtained by site-directed mutagenesis. The 3G3K mutant, characterized by a tag consisting of three lysines alternating with three
Modulation of penicillin acylase properties via immobilization techniques: One-pot chemoenzymatic synthesis of Cephamandole from Cephalosporin C
Terreni, Marco,Pagani, Giuseppe,Ubiali, Daniela,Fernandez-Lafuente, Roberto,Mateo, Cesar,Guisan, Jose M.
, p. 2429 - 2432 (2007/10/03)
The modulation of penicillin G acylase (PGA) properties via immobilization techniques has been performed studying the acylation of 7-aminocephalosporanic acid with R-mandelic acid methyl ester. PGA from Escherichia coli, immobilized onto agarose activated
