- Synthesis method of aztreonam monocyclic mother nucleus
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The invention discloses a synthesis method of an aztreonam monocyclic mother nucleus, and mainly relates to the technical field of pharmaceutical and chemical industry. The method comprises the stepsthat L-threonine is subjected to methyl esterification; terbutyloxycarbonyl anhydride is used for performing amino BOC protection; ammonia water is subjected to ammonolysis; under the catalysis of a solid basic catalyst, methyl-sulfuric-acyl reaction and sulfonation are performed; cyclization, deprotection and acidification are performed to obtain the aztreonam monocyclic mother nucleus. The raw materials are cheap and can be easily obtained; the yield is high; the cost is low; the synthesis method belongs to a green, energy-saving and environment-friendly practical technology.
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Paragraph 0046; 0050; 0051
(2019/06/13)
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- Synthetic method for aztreonam mother nucleus
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The invention provides a synthetic method for an aztreonam mother nucleus. The method uses sulfamic acid and ethyl bromoacetate as starting raw materials and produces the aztreonam mother nucleus through a chiral prosthetic group-induced 2+2 addition reaction. The method has the advantages of low price of raw materials and high yield, and does not use the high-risk chemical chlorosulfonic acid.
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Paragraph 0007; 0019
(2018/09/08)
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- Aztreonam primary ring synthesis method
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The invention discloses a synthesis method of an aztreonam main ring, which comprises the following steps: by using L-threonine as a raw material, carrying out amino protection, converting carboxyl group into amido sulfonic acid, carrying out cyclization reaction, and finally deprotecting to obtain the aztreonam main ring. The method is simple to operate and lower in cost, and the total yield is 48.7%. The produced aztreonam main ring is white solid powder, the specific rotatory power is -45 degrees, and the HPLC (high performance liquid chromatography) purity is 98.5% above. The quality of the product is high, and thus, the method is suitable for industrial production.
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Paragraph 0019; 0040; 0041
(2017/08/25)
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- Ammonia curved the monocyclic parent nucleus method for the preparation of
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The invention relates to a preparation of Aztreonam monocyclic parent nucleus method, in the method using benzyl chloroformate under strongly acidic conditions the protection, the sodium carbonate is used to carry out closed-loop reaction, the reaction is stable, is greatly improved yield, total yield of 48% the advantages.
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Paragraph 0030; 0035
(2017/01/26)
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- USEFUL COMBINATIONS OF MONOBACTAM ANTIBIOTICS WITH BETA-LACTAMASE INHIBITORS
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A pharmaceutical composition, comprising a combination of an antibiotically active compound of the formula (I): with a ?-lactamase inhibitor of one of the formulae (II) to (XIII) are active against Gram-negative bacteria, in particular such bacteria which have become resistant against antibiotics such as aztreonam, carumonam and tigemonam. Optionally the compositions may comprise another ?-lactamase inhibitor of one of the formulae (II) to (XIII), particularly of formula (V) or formula (VI).
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Page/Page column 98-99; 101-104
(2010/11/27)
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- Regioselective activation of aminothiazole(iminoxyacetic acid)acetic acid: An efficient synthesis of the monobactam aztreonam
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An efficient synthesis of the monobactam aztreonam [[2S-[2α,3β(Z)]]-3[[(2-amino-4-thiazolyl)[(1-carboxy-1- methylethoxy)imino]acetyl]amino]-2-methyl-4-oxo-1-azetidinesulfonic acid] (1) by acylation of α-aminoazetidinone 22 with the regioselectively activated aminothiazoleiminoxyacetic diacid 15 or 18 is described. Reaction of benzhydryl ester 10 with N-hydroxy-benzotriazole and dicyclohexylcarbodiimide followed by ester deprotection formed the monoacid amide 15. Alternatively, chemoselective transient silylation of the diacid 9 followed by activation with N-hydroxysuccinimide formed active ester 18. Acylation of α-aminoazetidinone 22 with amide 15 or ester 18 produced aztreonam (1) in 75-85% yield.
- Singh, Janak,Denzel, Theodor W.,Fox, Rita,Kissick, Thomas P.,Herter, Rolf,Wurdinger, Joseph,Schierling, Peter,Papaioannou, Chris G.,Moniot, Jerome L.,Mueller, Richard H.,Cimarusti, Christopher M.
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p. 863 - 868
(2013/09/06)
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- Process and intermediates for beta-lactams having aminothiazole(iminooxyacetic acid)acetic acid sidechains
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Disclosed herein are processes for preparing a compound of the formula STR1 in which a novel compound of the formula STR2 is reacted with a beta lactam of the formula STR3 by treatment with a base, wherein the symbols are as defined in the specification.
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- Stereoselective synthesis of cis-4-(substituted) monobactams from ethyl acetoacetate
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The stereoselective synthesis of cis-3-amino-4-methyl-2-oxoazetidine-1-sulphonic acid (25) from ethyl acetoacetate is described. Nitrosation of this compound and reduction of the resulting oxime gave the corresponding amine, which after treatment with different acyl halides, yielded the acylamino derivatives (6)-(8). Condensation with p-anisidine gave the enamines (12)-(14), which were then reduced to the β-amino acid esters (15)-(17). Stereoselective cyclization with Grignard reagents as base, and appropriate deprotection and sulphonation of the resulting β-lactams (18)-(20), led to the title compounds.
- Fernandez-Resa, Piedad,Herranz, Rosario,Conde, Santiago,Arribas, Enrique
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- Enantioselective Synthesis of (3S)-trans-4-(Substituted Methyl)monobactams from 2,3-O-Isopropylidene-D-glyceraldehyde
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The enantioselective synthesis of various (3S)-trans-4-(substituted methyl)-2-oxoazetidine-1-sulphonic acid derivatives from 2,3-O-isopropylidene-D-glyceraldehyde is described.Reaction of this aldehyde with trimethylsilyl cyanide gave a 80:20 ratio of the corresponding threo and erythro α-amino-nitriles, which by amino protection and subsequent treatment with basic hydrogen peroxide provided the corresponding α-amino carboxamides.Successive selective protection, activation, sulphonation and, finally, stereospecific cyclization of the threo α-carboxamide yielded (2S,4R)-3-benzyloxycarbonylamino-4-hydroxymethyl-2-oxoazetidine-1-sulphonic acid, an intermediate for the synthesis of the corresponding 4-acyloxymethyl-, 4-carbamoyloxymethyl-, 4-methylsulphonyloxy-methyl-, 4-iodomethyl-, and 4-methyl-2-oxozetidines.
- Herranz, Rosario,Conde, Santiago,Fernandez-Resa, Piedad,Arribas, Enrique
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p. 649 - 656
(2007/10/02)
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- 2-OXO-1-AZETIDINESULFONIC ACID SALTS
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Antibacterial activity is exhibited by beta-lactams having a sulfonic acid salt substituent in the 1-position and an amino or acylamino substituent in the 3-position.
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- (S)-3-Isocyanato-2-oxo-1-azetidinesulfonic acids
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3-Isocyanato-2-oxo-1-azetidinesulfonic acid salts are novel intermediates which are useful in processes for the preparation of 3-amino-2-oxo-1-azetidinesulfonic acid salts and 3-acylamino-2-oxo-1-azetidinesulfonic acid salts.
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- 4-alkylated monobactams. Chiral synthesis and antibacterial activity
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The synthesis of 4-alkylated monobactams by a variety of procedures is described. Two complementary procedures have been developed for the chiral synthesis of monobactams: (1) sulfonation of 4-alkyl-3-(protected)amino-2-azetidinones with various complexes of SO3; and (2) cyclization of β-mesyloxyacyl sulfamates derived from β-alkyl-β-hydroxy-α-amino acids. The most general procedure involves introduction of the alkyl group via a Grignard reaction on 6-APA-derived sulfones 23 or 24 followed by sulfonation. For the specific case of (3S,trans-)-3-amino-4-methylmonobactamic acid (48), cyclization of the β-mesyloxyacyl sulfamate 40 derived from (L)-threonine is the preferred route. The introduction of 4-alkyl groups into monobactams results in a decrease in activity against gram-positive bacteria, an increase in activity against gram-negative bacteria, and an increase in β-lactamase stability. Increasing the size of the alkyl group beyond methyl results in diminished intrinsic antibacterial activity. 4β-Alkylmonobactams display better β-lactamase stability than their 4α-counterparts.
- Cimarusti,Bonner,Breuer,et al.
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p. 2577 - 2589
(2007/10/02)
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- Sulfamated amino acid amides
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The process of this invention provides for the conversion of amino acid amides having the formula STR1 to 3-amino-2-oxo-1-azetidinesulfonic acid salts having the formula STR2 wherein one of R2 and R3 is hydrogen and the other is hydrogen, alkyl, cycloalkyl, phenyl or substituted phenyl and M≈ is hydrogen or a cation.
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- Monobactams. Stereospecific Synthesis of (S)-3-Amino-2-oxoazetidine-1-sulfonic Acids
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A facile, stereospecific synthesis of 3-amino-2-oxoazetidine-1-sulfonic acids (monobactams) by the cyclization of acyl sulfamates derived from β-hydroxy amino acids is described.
- Floyd, David M.,Fritz, Alan W.,Cimarusti, Christopher M.
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p. 176 - 178
(2007/10/02)
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- Monobactams. Preparation of (S)-3-Amino-2-oxoazetidine-1-sulfonic Acids from L-α-Amino-β-hydroxy Acids via Their Hydroxamic Esters
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The cyclization of the O-methylhydroxamates 13-15 afforded excellent yields of the 1-methoxyazetidinones 16-18.Reductive cleavage of the methoxy group gave N-1-unsubstituted azetidinones 9, 19, and 20 which were sulfonated and deprotected, yielding zwitterions 29-31.These materials serve as general intermediates for the preparation of a large variety of monobactam antimicrobial agents.
- Floyd, David M.,Fritz, Alan W.,Pluscec, Josip,Weaver, Eugene R.,Cimarusti, Christopher M.
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p. 5160 - 5167
(2007/10/02)
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