80082-62-8

Upstream product

• 92973-27-8 2-benzyloxycarbonylamino-4-O-chloroacetyl-2-deoxy-3-O-mesyl-D-threonamide 
• 80582-04-3 (3S-trans)-3-[[(phenylmethoxy)carbonyl]amino]-4-methyl-2-azetidinone 
• 32503-27-8 tetra(n-butyl)ammonium hydrogensulfate 
• 80542-82-1 cis-3-benzyloxycarbonylamino-4-methylazetidin-2-one 
• 112026-37-6 ethyl 2-(benzyloxycarbonylamino)acetoacetate 
• 112026-40-1 cis-3-benzyloxycarbonylamino-N-(4-methoxyphenyl)-4-methylazetidin-2-one 
• 112026-39-8 ethyl 3-(p-anisidino)-2-(benzyloxycarbonylamino)butanoate 
• 112026-38-7 ethyl (p-anisidino)-2-(benzoyloxycarbonylamino)but-2-enoate 
• 13139-17-8 N-(Benzyloxycarbonyloxy)succinimide 
• 2052-49-5 tetra(n-butyl)ammonium hydroxide 
• 80082-65-1 (3S-trans)-3-Amino-4-methyl-2-oxo-1-azetidinesulfonic acid 
• 80582-09-8 (2R-cis)-3-amino-2-methyl-4-oxo-1-azetidine-sulfonic acid 
• 75315-63-8 N-(benzyloxycarbonyl)succinimide 
• 80082-51-5 N-benzyloxycarbonyl-O-methanesulfonyl-L-threonine amide 

Downstream Products

• 80082-65-1 (3S-trans)-3-Amino-4-methyl-2-oxo-1-azetidinesulfonic acid 
• 80582-04-3 (3S-trans)-3-[[(phenylmethoxy)carbonyl]amino]-4-methyl-2-azetidinone 
• 115887-91-7 cis-3-benzyloxycarbonylamino-4-methyl-2-oxoazetidine-1-sulphonic acid sodium salt 

Relevant academic research and scientific papers

Toward Orally Absorbed Prodrugs of the Antibiotic Aztreonam. Design of Novel Prodrugs of Sulfate Containing Drugs. Part 2

Aztreonam, first discovered in 1980, is an FDA approved, intravenous, monocyclic beta-lactam antibiotic. Aztreonam is active against Gram-negative bacteria and is still used today. The oral bioavailability of aztreonam in humans is less than 1%. Herein we describe the design and synthesis of potential oral prodrugs of aztreonam.

METHODS OF SYNTHESIZING AZTREONAM DERIVATIVES

Disclosed herein are aztreonam derivatives, therapeutic methods of using the aztreonam derivatives, and methods of synthesizing aztreonam derivatives. The aztreonam derivatives can be administered orally to provide orally bioavailable aztreonam.

AZTREONAM DERIVATIVES AND USES THEREOF

Disclosed herein are aztreonam derivatives, therapeutic methods of using the aztreonam derivatives, particularly in combination with β-lactamase inhibitors, and pharmaceutical compositions thereof. The aztreonam derivatives can be administered orally to provide orally bioavailable aztreonam.

Crystalline anhydrous aztreonam

The crystalline anhydrous form of [3S-[3α(Z), 4β]]-3-[[(2-amino-4-thiazolyl) [(1-carboxy-1-methylethoxy)imino]acetyl]amino]-4-methyl-2-oxo-1-azetidinesulfonic acid is prepared.

Stereoselective synthesis of cis-4-(substituted) monobactams from ethyl acetoacetate

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.

2-OXO-1-AZETIDINESULFONIC ACID SALTS

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.

Enantioselective Synthesis of (3S)-trans-4-(Substituted Methyl)monobactams from 2,3-O-Isopropylidene-D-glyceraldehyde

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.

Sulfamated amino acid amides

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.

Monobactams. Stereospecific Synthesis of (S)-3-Amino-2-oxoazetidine-1-sulfonic Acids

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.