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| | Cefmenoxime hydrochloride Basic information | | Synthesis |
| Product Name: | Cefmenoxime hydrochloride | | Synonyms: | 8-[2-(2-amino-1,3-thiazol-4-yl)-2-methoxyimino-acetyl]amino-4-[(1-methyltetrazol-5-yl)sulfanylmethyl]-7-oxo-2-thia-6-azabicyclo[4.2.0]oct-4-ene-5-carboxylic acid hydrochloride (2:1);7-[[(2-Amino-4-thiazolyl)(methoxyimino)acetyl]amino]-3-[[(1-methyl-1H-tetrazol-5-yl)thio]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid hemihydrochloride;7beta-[2-(2-Aminothiazol-4-yl)-(Z)-2-(methoxyiminoacetamido)]-3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]ceph-3-em-4-carboxylic acid hemihydrochloride;Bestcall;Bestron;Cemix;SCE-1365(free acid);Tacef | | CAS: | 75738-58-8 | | MF: | C16H18ClN9O5S3 | | MW: | 548.01 | | EINECS: | 278-299-4 | | Product Categories: | CEFMAX;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;Sulfur & Selenium Compounds | | Mol File: | 75738-58-8.mol |  |
| | Cefmenoxime hydrochloride Chemical Properties |
| Melting point | >175°C (dec.) | | storage temp. | under inert gas (nitrogen or Argon) at 2-8°C | | solubility | DMSO (Slightly, Heated), Methanol (Slightly) | | form | Solid | | color | Off-White to Pale Yellow | | InChIKey | HZYJYGJIOCXOTH-AJVJENPNNA-N | | SMILES | C(C1=C(CS[C@]2([H])[C@H](NC(=O)/C(/C3N=C(N)SC=3)=N\OC)C(=O)N12)CSC1=NN=NN1C)(=O)O.Cl |&1:5,7,r| |
| | Cefmenoxime hydrochloride Usage And Synthesis |
| Synthesis | The main methods for preparing cephalosporins include chemical synthesis and enzymatic methods, as well as other methods such as gene-regulated biosynthesis. However, chemical synthesis remains the dominant method, with semi-synthetic methods based on major antibiotic nuclei and methods that produce cephalosporins from penicillin through oxidation, ring expansion, and rearrangement being widely used. The structural formula of cefotaxime hydrochloride is as follows: [Image of cefotaxime hydrochloride structure shown in Figure 1] Due to the chemical instability of the cephalosporin nucleus, the more reactions it participates in, the more difficult it is to control the quality of the final product. Therefore, according to literature reports, cefotaxime hydrochloride can be synthesized via the following synthetic route.
Route A: This route involves reacting the core of 7-amino-3-(1-methyl-1H-tetrazole-5-thiomethyl)cephalosporanic acid salt (7-ACA-MMT) with a 4-halo-2-methoxyimino-butyric acid derivative, followed by cyclization with sulfur to obtain the target product.
Figure 2 shows the synthetic route A for cefotaxime hydrochloride.
This route is cumbersome and has a very low yield. The main raw material, the 4-halo-2-methoxyimino-butyric acid derivative, is not readily available in large quantities on the market. Its activation must be carried out at low temperatures for a long time, which is time-consuming and energy-intensive. Furthermore, it involves numerous side reactions, resulting in unsatisfactory product yield and purity. Therefore, this route was abandoned.
Route B: This involves first synthesizing 7-[2-(2-amino-4-thiazolyl)-2(Z)-methoxyiminoacetic acid (ATMAA, part B, abbreviated as aminothiazolyl) and 7-aminocephalosporanic acid (part C, abbreviated as 7-ACA) to obtain 7-[2-(2-amino-4-thiazolyl)-2(Z)-methoxyiminoacetic acid]aminocephalosporanic acid (abbreviated as cephalothiazolyl), and then reacting it with 1-methyl-5-mercapto-1H-tetrazole to synthesize the target product, cefotaxime.
Figure 3 shows the synthetic route B for cefotaxime hydrochloride.
Experiments revealed that the product produced by the reaction of cefotaxime acid with 1-methyl-5-mercapto-1H-tetrazole (MMT) via this route was of poor quality and had a low yield. The main reason for this was believed to be the prolonged (3.5 h) immersion of the 7-ACA cephalosporin nucleus in aqueous solution at 55–60 °C, which partially destroyed the nucleus, darkened the system color, and resulted in a lower purity product, significantly increasing the difficulty of subsequent purification. Route C: This route involves synthesizing 7-aminocephalosporanic acid (7-ACA) with 1-methyl-5-mercapto-1H-tetrazole (MMT) to obtain 7-amino-3-(1-methyl-1H-tetrazole-5-thiomethyl)cephalosporanic acid salt (7-ACA-MMT), which is then condensed with 2-(2-amino-4-thiazolyl)-2(Z)-methoxyiminoacetic acid-2-benzothiazolyl thioester (MAEM, abbreviated as AE-active ester) to obtain the target compound, cefotaxime.
Figure 4 shows the synthetic route C for cefotaxime hydrochloride.
This route is simple to operate, and after experimental investigation, the yield and quality are relatively ideal, making it a suitable route for the synthesis of the target compound. | | Description | Cef menoxime hydrochloride is a third generation cephalosporin antibiotic.
Structurally, it possesses the (1-methyl-lH-tetrazol-5-yl)thiomethyl moiety in
the 3-position; like several other compounds containing this structural element
(moxalactam, cefoperazone, cefamandol), bleeding linked to vitamin K interaction
has been reported. Cefmenoxime has activity similar to cefotiuime, ceftizoxime
and moxalactam against E.coli, C. diversus, Klebsiella, P. Mirabilis, Salmonella,
Shigella, Neiseria spp., S. pyogenes, S. Pneumoniae, and g. influenzae. It is
relatively ineffective against Pseudomonas and Bacteroidea. | | Originator | Takeda (Japan) | | Uses | A third generation cephalosporin antibiotic with strong antimicrobial activities against Streptococcus pneumoniae, Haemophilus influenzae and Moraxella subgenus Branhamella catarrhalis that were 3 major aerobic bacteria from sinusitis. | | Uses | antibacterial | | Definition | ChEBI: The hemihydrochloride salt of cefmenoxime. | | Brand name | Cefmax (TAP);TACEF;BESTCALL. | | General Description | Cefmenoxime was synthesized by Takeda Pharmaceutical Co. in 1978. It contains aminothiazole and methoxyimino groups in the 7-acyl position and a methyltetrazole group at the 3 position of the cephem nucleus. Cefmenoxime has a wide activity spectrum against gram-positive and gram-negative bacteria, including anaerobes, except Staphylococcus aureus. Cefmenoxime is a member of the so-called third-generation cephalosporins, a recently introduced class of clinically important antibiotics. |
| | Cefmenoxime hydrochloride Preparation Products And Raw materials |
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