- A rapid and cheap synthesis of cephalosporins
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A fast, cheap and pollution free microwave assisted method for the synthesis of cephalosporin and its comparison with conventional method in terms of yield and reaction time were described.
- Kidwai, Mazaahir,Bhushan, Kumar Ranjan,Misra, Preeti
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Read Online
- Cefazedone synthesis method
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The invention discloses a cefazedone synthesis method. A compound II reacts with 7-ACA to prepare a compound III, and the compound III reacts with a compound IV to prepare the final product cefazedone. The method has the advantages of simple reaction process, easiness in operation, high total yield and high purity of the product, few byproducts, and suitableness for industrial production.
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Paragraph 0024-0032
(2019/12/25)
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- Preparation technology of cefazedone sodium
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The invention belongs to the technical field of medicine, and discloses a preparation technology of cefazedone sodium. 3,5-dichloropyridone acetic acid and pivaloyl chloride are taken as the raw materials to synthesize mixed acid anhydrides; and then cefazedone sodium is obtained after salt forming reactions between mixed acid anhydrides and an intermediate prepared from 7-aminocephalosporanic acid and thiol tetrazole. A mixed solvent is used in 3-substitution, the reaction becomes more stable and softer, the byproducts are reduced; in acylation reactions, mixed acid anhydrides are used, the activity is high, 7-acylation reactions are promoted, and thus the yield and purity of cefazedone sodium are high.
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Page/Page column 6-9
(2019/05/08)
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- A head west spore alkone sodium synthetic method (by machine translation)
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The invention belongs to the field of medical technology, discloses a head-west spore alkone sodium synthetic method. In order to 3, 5 - dichloro pyridone acetic acid and two sulfur thioalcohol thiazole as raw material synthetic active ester, with the 7 - amino cephalosporanic acid and mercapto tetrazole generated intermediate reaction, into west spore alkone sodium salt obtained by the head. The invention in 3 - substituted using mixed in the solvent, the reaction is more stable and smooth, reducing the generation of by-products, in the acylation reaction using the active ester, active high, conducive to the 7 - position of the acylation reaction, the resulting west spore alkone sodium yield and purity are relatively high. (by machine translation)
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Paragraph 0034; 0035; 0038; 0039; 0042; 0043; 0046; 0047
(2019/04/26)
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- Preparation method of cefazedone sodium compound
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The invention discloses a preparation method of a cefazedone sodium compound. 7-ACA and a compound III react to prepare a compound IV, and the compound IV and a compound V have an amidation reaction,and are salified and refined to obtain a competitive product of cefazedone sodium (I). The process route of the reaction is simple, the total yield and the purity are high, and the method is suitablefor industrial production.
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Paragraph 0017; 0030-0038
(2018/08/04)
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- Cephalosporins anti-infective drug preparation method
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The invention relates to a preparation method for a cephalosporin anti-infective drug-cefazedone sodium, belonging to the field of pharmaceutical synthesis. According to the invention, the method uses GCLE as a raw material to substitute 7-ACA and overcomes the defects of low yield, high pollution and the like in prior art; the preparation method with mild reaction conditions, little side reaction and simple process is provided; meanwhile, the method has the advantages of cheap and easily-available raw materials, low cost, high product yield, high product purity and applicability to industrial production.
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Paragraph 0018; 0031; 0032; 0040; 0041; 0049; 0050
(2018/03/01)
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- Preparation method of cefazolin sodium with previous research quality and medicine preparation of cefazolin sodium
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The invention discloses a preparation method of cefazolin sodium with previous research quality. The preparation method is characterized by comprising the following steps: (1) adding a boron trifluoride-dimethyl carbonate solution into dimethyl carbonate; stirring and adding 2-sulfydryl-5-methyl-1,3,4-thiadiazole and 7-ACA (Acetic Acid) to react; after the reaction is finished, adding dimethyl formamide and dropwise adding hydrochloric acid; adjusting the temperature to 25 to 35 DEG C and reacting for 60 minutes; filtering and washing with acetone; drying in vacuum to obtain a TDA (Toluene Diamine) crude product; (2) preparing mixed anhydride from dichloromethane, tetrazolyl acetic acid, triethylamine and pivaloyl chloride; (3) adding the TDA crude product into a dichloromethane solvent; cooling and dropwise adding tetramethyl guanidine; dropwise adding the mixed anhydride to react, and purifying and refining a crystal through a low-temperature acetonitrile-water extraction process after extraction and crystallization. With the adoption of the preparation method provided by the invention, the moisture content of the product can be reduced and residues of the solvent can be reduced; the increasing of related substances can be effectively reduced, a freeze-drying technology is not used and the production efficiency is improved.
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Paragraph 0022-0024
(2017/02/23)
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- On the substrate preference of glutaryl acylases
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The substrate preferences of three acylases - two wild-type enzymes and an evolved variant obtained by directed evolution - which are prototypical enzymes for glutaryl-7-ACA acylase and cephalosporin C acylase subfamilies, have been investigated. A preliminary screening of enzymes' performances on a large set of substrates has been carried out by a colorimetric assay performed in 96-well plates and by a pH-Stat monitoring the hydrolytic activities. Subsequently, kinetic data for selected substrates have been determined, thus elucidating the substrate preference of members of glutaryl-7-ACA acylase vs. cephalosporin C acylase subfamilies. These achievements pave the way to the ability of choosing the best enzyme for the hydrolysis of different compounds of industrial importance.
- Rosini, Elena,Monelli, Claudia Stella,Pollegioni, Loredano,Riva, Sergio,Monti, Daniela
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experimental part
p. 52 - 58
(2012/04/11)
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- Glutaryl Acylases: One-Reaction Enzymes or Versatile Enantioselective Biocatalysts?
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A significant broad substrate specificity, that crosses over the usual β-lactam derivatives, has been observed with an industrial glutaryl-7-aminocephalosporanic acid acylase (GA). This enzyme possesses significant enantioselective amidase and even esterase activity, with a stereopreference for the S-enantiomer. The easy separation of products from unreacted reagents, possessing different physical-chemical properties, is achieved by solvent extraction, avoiding chromatography or distillation during reaction work-up.
- Raimondi, Stefano,Monti, Daniela,Pagnoni, Ugo Maria,Riva, Sergio
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p. 783 - 789
(2007/10/03)
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- Process for preparing cephalosporin intermediates
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Processes for the preparation of stable, crystalline cephalosporin intermediates of the formula STR1 wherein X is HI or HCl, and Nu and Nu≈ are certain N-containing heterocyclic rings attached via a sulfur atom or a ring nitrogen atom, respectively, which are substantially free of the Δ2 isomer; processes for intermediates in the preparation of the above compounds; and processes for the preparation of broad-spectrum cephalosporin antibiotics.
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- Use of Bistrimethylsilylated Intermediates in the Preparation of Semisynthetic 7-Amino-3-substituted-cephems. Expedient Syntheses of a New 3-cephalosporin
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Several "one-pot" methods for conversion of 7-ACA (6) to a variety of 7-amino-3-(ammoniomethyl)- or 7-amino-3-methyl>cephalosporin derivatives via bistrimethylsilylated intermediates are presented.For example, bistrimethylsilylation of 7-ACA (6) in 1,1,2-trichlorotrifluoroethane (Freon TF) using HMDS and 3 mol percent TMSI, followed by treatment with 1.15 equiv of TMSI and subsequent reactions with tertiary alicyclic or heteroaromatic amines or heteroaromatic thiols, led to the desired products in good yields.Alternatively, novel reaction of the bistrimethylsilylated derivative 15 with amine/TMSI adducts in Freon TF at 35 deg C provided an alternative approach to some 7-amino-3-(ammoniomethyl)cephalosporins.The solvent dependence of Δ3/Δ2 isomer ratios in quaternization reactions of 11 with N-methylpyrrolidine is presented.Hypotheses for the explanation of experimental results observed on reaction of 15 in Freon TF with amine/TMSI adducts are presented.Acylation of 17 (X = Cl, I) with 8 in aqueous THF provided 18 (BMY-28142) as its sulfate salt in overall yields of 18percent and 43percent, respectively, from 7-ACA (6).
- Walker, Donald G.,Brodfuehrer, Paul R.,Brundidge, Steven P.,Shih, Kun Mao,Sapino, Chester
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p. 983 - 991
(2007/10/02)
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- Cephalosporin intermediates
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Stable, crystalline cephalosporin intermediates of the formula STR1 wherein X is HI or HCl and Nu and Nu≈ are certain N-containing heterocyclic rings attached via a sulfur atom or a ring nitrogen atom, respectively, which are substantially free of the Δ2 isomer; processes for, and intermediates in, the preparation of the above compounds; and processes for the preparation of broad-spectrum cephalosporin antibiotics.
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- Process for the preparation of 3-substituted 7-aminocephalosporanic acids
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A 3-substituted 7-aminocephalosporanic acid of formula: STR1 where R1 is hydrogen, methyl of methoxy, Y is nitrogen, oxygen sulphur or a sulphoxide group, R2 is a group selected from among azide or from a radical having the formula R3 --S-- where R3 may be, among others, alkyl, aliphatic acyl, methyl and chlorine or methoxy substituted aromatic acyl, is prepared. A compound of formula STR2 (X being chlorine, carbamoyloxy or acetoxy) is added to a medium constituted by water, a compound which may be nitric acid or a compound of formula R3 --SH and a tertiary organic base. With a reaction isoelectric pH regulator, the mixture takes on a specific process pH analytical profile, the compounds of said mixture being reacted together at particular temperatures and with a specific process time.
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- Process for the preparation of solutions of 7-aminocephalosporanic acids
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A process for the preparation of solutions of 7-aminocephalosporanic acids wherein there is obtained a salt of the general formula III: STR1 where R1 may be a group selected from among hydrogen, methyl, or a low molecular weight alkoxy, R2 is a group selected from among methyl, methoxy, azido, chlorine, carbamoylmethyl, acetoxy, thiomethyl, phenylthiomethyl and others, x means from 3 to 5 carbon atoms and y means from 2 to 4 carbon atoms is disclosed. The process is based on the reaction of a compound of formula I STR2 with a bicyclic amidine.
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- Novel oximes
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Novel syn isomers of 3-substituted-7-amino-thiazolyl-acetamido-cephalosporanic acid compounds of the formula STR1 wherein R is selected from the group consisting of alkyl of 1 to 5 carbon atoms, cycloalkyl of 3 to 5 carbon atoms and --CH2 --S--R1, R1 is selected from the group consisting of 2-methyl-1,3,4-thiadiazolyl, 1-methyl tetrazolyl, acyl of an organic carboxylic acid of 2 to 4 carbon atoms and STR2 R2 is selected from the group consisting of alkyl and alkoxy of 1 to 4 carbon atoms and A is selected from the group consisting of hydrogen, alkali metal, alkaline earth metal, magnesium and a non-toxic, pharmaceutically acceptable organic amine having antibiotic activity and novel intermediates and process for their preparation.
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- Cephalosporin antibiotics
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Novel cephalosporin antibiotic derivatives.
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- Cephalosporin antibiotics
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Novel cephalosporin antibiotic derivatives.
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- Cephalosporin antibiotics
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Novel cephalosporin antibiotic derivatives.
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- 3-Heterothio[(thioalkyl)thioacetyl]cephalosporanic derivatives
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3-Heterothio[(thioalkyl)thioacetyl]cephalosporin derivatives which have the formula STR1 wherein R is hydrogen, lower alkyl, phenyl-lower alkyl, tri(lower alkyl)silyl, a salt forming ion, or the group STR2 R 1 is hydrogen, lower alkyl, phenyl, thienyl of furyl; R2 and R6 each is hydrogen or lower alkyl; R3 and R5 each is lower alkyl, phenyl or phenyl-lower alkyl; and R4 is a five- or six-membered nitrogen and/or sulfur or oxygen-containing ring system; are useful as antibacterial agents.
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- 3-Heterothiomethyl-7α-methoxy-7β-tetrazolylmethylthioacetamido-3-cephem derivatives
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7α-Methoxy-7β-tetrazolylmethylthioacetamido-3-cephem derivatives which have a heterothiomethyl substituent in the 3-position are novel compounds which are useful as antimicrobial agents.
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- Isothiourea substituted cephalosporin derivatives
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Novel cephalosporin and penicillin antibiotic derivatives.
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- 3-Heterothio derivatives of (carbamoylthioacetyl)cephalosporins
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3-Heterothio(carbamoylthioacetyl)cephalosporin derivatives of the general formula EQU1 wherein R is hydrogen, lower alkyl, phenyl-lower alkyl, tri(lower alkyl)silyl, a salt forming ion or the group EQU2 R1 is hydrogen, lower alkyl, phenyl, thienyl, or pyridyl; R2 is lower alkyl or phenyl-lower alkyl; R3 is a five or six membered nitrogen, sulfur and/or oxygen containing ring system; and R4 is lower alkyl, phenyl or phenyl-lower alkyl; are useful as antibacterial agents.
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- 3-Heterothio derivatives of [(alkoxycarbonyl)oxyacetyl]cephalosporins
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3-Heterothio derivatives of [(alkoxycarbonyl)oxyacetyl]cephalosporins which have the formula SPC1 tri(lower Wherein R1 is hydrogen, lower alkyl, phenyl, phenyl-lower alkyl or certain heterocyclic groups; R2 is lower alkyl; R3 is hydrogen, lower alkyl, tri(lower alkyl)silyl, tri(lowe alkyl)stannyl, a salt forming ion, or EQU1 R is lower alkyl, phenyl, or phenyl-lower alkyl; R4 is a five-membered nitrogen and sulfur or oxygen-containing ring system; are useful as antibacterial agents.
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- 3-Heterothio derivatives of (α-thiocarbonylamino) cephalosporins
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3-Heterothio(α-thiocarbonylamino)cephalosporin derivatives of the general formula STR1 wherein R is hydrogen, lower alkyl, phenyl-lower alkyl, tri(lower alkyl)silyl, trihaloethyl, a salt forming ion or the group STR2 R1 is hydrogen, lower alkyl, cyclo-lower alkyl, unsaturated cyclo-lower alkyl, phenyl, substituted phenyl or thienyl; R2 and R5 each is hydrogen or lower alkyl; R3 is a five or six membered nitrogen, sulfur and/or oxygen containing ring system; and R4 is lower alkyl, phenyl or phenyl-lower alkyl; are useful as antibacterial agents.
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- 3-Tetrazolyl and other derivatives of [[(alkoxy)thiocarbonyl]oxy]acetyl cephalosporins
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3-Heterothio derivatives of [[(alkoxy)thiocarbonyl]oxy]acetyl cephalosporins having the formula EQU1 wherein R is hydrogen, lower alkyl, phenyl-lower alkyl, tri(lower alkyl)stannyl, tri(lower alkyl)silyl, a salt forming ion or the group EQU2 R1 is hydrogen, lower alkyl, phenyl, pyridyl, thienyl or furyl; R2 is lower alkyl or phenyl-lower alkyl; R3 is 1-oxopyridinyl or a five membered heterocycle containing only nitrogen and carbon or nitrogen, carbon and oxygen or sulfur in the ring; R4 is lower alkyl, phenyl or phenyl-lower alkyl; are useful as antibacterial agents.
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- 3-Alkylthio and 3-heterothio derivatives of [[(thioalkoxy)thiocarbonyl]oxy]acetyl cephalosporins
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3-Alkylthio- and 3-heterothio derivatives of [[(thioalkoxy)thiocarbonyl]oxyl]acetylcephalosporins having the general formula EQU1 wherein R is hydrogen, lower alkyl, phenyl-lower alkyl, tri(lower alkyl)stannyl, tri(lower alkyl)silyl, a salt forming ion or the group EQU2 R1 is hydrogen, lower alkyl, phenyl, pyridyl, thienyl or furyl; R2 is lower alkyl or phenyl-lower alkyl; R3 is lower alkyl, a five-membered heterocycle containing only nitrogen and carbon or nitrogen, carbon and oxygen or sulfur in the ring or pyridine-N-oxide; R4 is lower alkyl, phenyl or phenyl-lower alkyl; are useful as antibacterial agents.
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- 3-Heterothio[(oxyalkyl)thioacetyl]cephalosporin derivatives
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3-Heterothio[(oxyalkyl)thioacetyl] cephalosporin derivatives which have the formula EQU1 wherein R is hydrogen, lower alkyl, phenyl-lower alkyl, tri (lower alkyl) silyl, a salt forming ion, or the group EQU2 R1 is hydrogen, lower alkyl, phenyl, thienyl or furyl; R2 and R6 each is hydrogen or lower alkyl; R3 and R5 is lower alkyl, phenyl or phenyl-lower alkyl; and R4 is a five- or six-member nitrogen and/or sulfur or oxygen-containing ring system; are useful as antibacterial agents.
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