2133-34-8

Usage

Uses

Used in Pharmaceutical Industry:
(S)-(-)-2-Azetidinecarboxylic acid is used as a specific proline antagonist for the synthesis of abnormally high molecular weight polypeptides. It serves as a useful intermediate in the creation of these polypeptides, which can have significant implications in drug development and therapeutic applications.
Used in Research and Development:
In the field of research and development, (S)-(-)-2-Azetidinecarboxylic acid is utilized as a collagen synthesis inhibitor and a protein folding antagonist. These properties make it a valuable tool for studying the mechanisms of protein synthesis and folding, which can contribute to the understanding and treatment of various diseases related to protein misfolding.
Used in Analytical Chemistry:
(S)-(-)-2-Azetidinecarboxylic acid is employed as a standard in liquid chromatography-mass spectrometry (LC-MS). Its use as a standard aids in the accurate analysis and identification of other compounds in complex mixtures, ensuring precise and reliable results in various analytical applications.

Biochem/physiol Actions

Azetidine-2-carboxylic acid (AZC) triggers protein aggregation or upregulates the expression of an aggregation-prone mutant protein, upon interference with nascent protein folding.

Safety Profile

Moderately toxic by subcutaneousroute. An experimental teratogen. Other experimentalreproductive effects. When heated to decomposition itemits toxic fumes of NOx.

InChI:InChI=1/C4H7NO2/c6-4(7)3-1-2-5-3/h3,5H,1-2H2,(H,6,7)/t3-/m0/s1

Upstream product

• 485-80-3 S-adenosyl-L-methionine 
• 87-69-4 L-Tartaric acid 
• 921600-20-6 dimethyl (1'S)-1-(1'-methyl)benzylazetidine-2,2-dicarboxylate 
• 204274-33-9 (2S,1'S)-1-(1'-methyl)benzylazetidine-2-carboxylic acid 
• 249734-39-2 methyl (2S,αR)-N-α-methylbenzylazetidine-2-carboxylate 
• 869800-26-0 (S)-1-((S)-1-Phenyl-ethyl)-azetidine-2-carboxylic acid; hydrochloride 
• 247051-66-7 benzyl [1(1S,2S)]-1-(1-phenyl-ethyl)-azetidine-2-carboxylate 
• 69994-45-2 (2S)-1-benzoylazetidine-2-carboxylic acid 
• 307316-14-9 (R)-4-amino-2-chlorobutyric acid 
• 129740-14-3 tert-butyl (2S)-azetidine-2-carboxylate 

Downstream Products

• 96287-28-4 (S)-2-Azetidincarbonsaeure-ethylester-hydrochlorid 
• 34441-14-0 (2S:3'S:3''S)-N-[N-(3-amino-3-carboxypropyl)-3-amino-3-carboxypropyl]-azetidine-2-carboxylic acid 
• 80900-94-3 L-1-<3-(acetylthio)-1-oxopropyl>-2-azetidinecarboxylic acid 
• 51077-14-6 (S)-1-(t-butoxycarbonyl)azetidine-2-carboxylic acid 
• 25654-52-8 (2S)-1-(benzyloxycarbonyl)azetidine-2-carboxylic acid 
• 77856-45-2 (S)-azetidine-2-carboxylic acid benzyl ester 
• 55033-06-2 2(S),3'(S)-N-(3-amino-3-carboxypropyl)-azetidine-2-carboxylic acid 
• 30248-47-6 N-nitrosoazetidine-2-carboxylic acid 
• 128120-94-5 (S)-Azetidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-(2-oxo-2-phenyl-ethyl) ester 
• 69994-45-2 (2S)-1-benzoylazetidine-2-carboxylic acid 
• 958350-50-0 C₂₀H₂₈N₂O₇ 
• 90599-96-5 C₁₃H₂₂N₂O₆ 
• 153704-88-2 (S)-1-benzyl 2-tert-butyl azetidine-1,2-dicarboxylate 
• 37712-76-8 (S)-1-acetylazetidine-2-carboxylic acid 

Relevant academic research and scientific papers

Azetidine-Containing Alkaloids Produced by a Quorum-Sensing Regulated Nonribosomal Peptide Synthetase Pathway in Pseudomonas aeruginosa

Pseudomonas aeruginosa displays an impressive metabolic versatility, which ensures its survival in diverse environments. Reported herein is the identification of rare azetidine-containing alkaloids from P. aeruginosa PAO1, termed azetidomonamides, which are derived from a conserved, quorum-sensing regulated nonribosomal peptide synthetase (NRPS) pathway. Biosynthesis of the azetidine motif has been elucidated by gene inactivation, feeding experiments, and biochemical characterization in vitro, which involves a new S-adenosylmethionine-dependent enzyme to produce azetidine 2-carboxylic acid as an unusual building block of NRPS. The mutants of P. aeruginosa unable to produce azetidomonamides had an advantage in growth at high cell density in vitro and displayed rapid virulence in Galleria mellonella model, inferring functional roles of azetidomonamides in the host adaptation. This work opens the avenue to study the biological functions of azetidomonamides and related compounds in pathogenic and environmental bacteria.

Multigram-scale and column chromatography-free synthesis of L-azetidine-2-carboxylic acid for the synthesis of nicotianamine and its derivatives

Multigram-scale synthesis of L-azetidine-2-carboxylic acid from L-aspartic acid was achieved in 13 conventional synthetic steps, without the need for purification by silica-gel column chromatography and expensive reagents. Nicotianamine and its fluorescence-labeled derivatives could be obtained from this synthetic strategy.

Preparation of enantiopure 2-acylazetidines and their reactions with chloroformates

Enantiopure 1-phenylethylazetidine-2-carboxylates and 2-acylazetidines were prepared and reacted with chloroformates to yield α-chloro-γ-amino butyric acid esters and ketones from ring opening reaction of azetidinium ion intermediate in a completely regio- and stereoselective manner.

Efficient route to (S)-azetidine-2-carboxylic acid

A new and efficient route to (S)-azetidine-2-carboxylic acid (>99.9% ee) in five steps and total yield of 48% via malonic ester intermediates was established. As the key step, efficient four-membered ring formation (99%) was achieved from dimethyl (S)-(1′-methyl)benzylaminomalonate by treating with 1,2-dibromoethane (1.5 eq) and cesium carbonate (2 eq) in DMF. Krapcho dealkoxycarbonylation of dimethyl (1′S)-1-(1′-methyl) benzylazetidine-2,2-dicarboxylate, the product of this cyclization procedure, proceeded with preferential formation (2.7:1, 78% total yield) of the desired (2S,1′S)-monoester, with the help of a chiral auxiliary which was introduced on the nitrogen atom. The undesired (2R,1′S)-isomer could be converted to that with proper stereochemistry, by a deprotonation and subsequent reprotonation step. Finally, lipase-catalyzed preferential hydrolysis of the (2S,1′S)-monoester and subsequent deprotection provided enantiomerically pure (S)-azetidine-2-carboxylic acid in a 91% yield from the mixture of (2S,1′S)- and (2R,1′S)-isomers.

Practical asymmetric preparation of azetidine-2-carboxylic acid

Facile and straightforward syntheses of both enantiomers of azetidine-2-carboxylic acid are described. The syntheses depart from inexpensive chemicals and allow for the production, in five to six steps, of practical quantities of each enantiomer. Synthetic highlights include the construction of the azetidine ring using an intramolecular alkylation and the use of optically active α-methylbenzylamine as chiral auxiliary.

PROCESS FOR PRODUCING OPTICALLY ACTIVE AZETIDINE-2-CARBOXYLIC ACID

The present invention provides an efficient, simple, and commercially advantageous process for producing optically active azetidine-2-carboxylic acid, which is an important material for medicines. The process includes the steps of halogenating an optically active N-protected 4-amino-2-hydroxybutyric acid following inversion of the configuration to produce an optically active N-protected 4-amino-2-halobutyryl halide; hydrolyzing the halide; deprotecting the amino group of the hydrolyzed product to produce an optically active 4-amino-2-halobutyric acid; cyclizing the product in an alkaline aqueous solution; and then protecting the amino group of the cyclized product to produce an optically active N-protected azetidine-2-carboxylic acid. The present invention also provides an optically active N-protected 4-amino-2-halobutyryl halide represented by general formula (2): (wherein P represents a protective group for the primary amino group; * indicates that the carbon atom is asymmetric; and each of X and Y independently represents a halogen atom), which is useful for producing the optically active azetidine-2-carboxylic acid.

Process for cyclizing optically active 4-amino-2-halogenobutyric acids

The invention provides a process for producing optically active azetidine-2-carboxylic acid with good efficiency, expedience, and commercial advantage, which comprises cyclizing an optically active 4-amino-2-halogenobutyric acid in an optical yield of as high as 90% or more. It is a process for producing optically active azetidine-2-carboxylic acid of the general formula (2), in which * denotes an asymmetric carbon atom, which comprises cyclizing an optically active 4-amino-2-halogenobutyric acid of the general formula (1), in which X represents a halogen atom and * denotes an asymmetric carbon atom, in the presence of an oxide of an alkaline earth metal, a hydroxide of an alkaline earth metal excepting barium, or an organic amine.

PROCESS FOR PRODUCING OPTICALLY ACTIVE AZETIDINE-2-CARBOXYLIC ACIDS

An optically active N-protected azetidine-2-carboxylic acid (5) can be produced by preparing an optically active 4-amino-2-halobutyric acid (3), ???by halogenating an optically active 3-hydroxy-2-pyrrolidinone (1) with inversion of configuration to prepare an optically active 3-halo-2-pyrrolidinone (2) followed by hydrolysis or, ???by halogenating an optically active 4-amino-2-hydroxybutyric acid ester (6) with inversion of configuration to prepare an optically active 4-amino-2-halobutyric acid ester (7) followed by hydrolysis or, ???by halogenating the compound (6) with inversion of configuration to prepare the compound (7), cyclizing the same to prepare the compound (2) followed by hydrolysis,???further cyclizing the compound (3) followed by treating the reaction product with an amino group-protecting agent.The optical purity of the thus-obtained compound (5) can be improved further by recrystallization.

Synthesis of chiral bicyclic azetidine derivatives

(2S)-N-Benzoyl-2-azetidinecarboxylic acid was converted into several derivatives of (5R)-1-azabicycloheptane via lactamization of 3-((2R)-azetidine)propanoic acid, subsequent aldol reaction and reduction. The structures of three stereoisomers of (5R)-3-(hydroxy-(4-nitrophenyl)methyl)-1-azabicyclo[3.2.0]heptan-2-one were determined by X-ray crystallography.

Bioresolution of N-acylazetidine-2-carboxylic acids

PCT No. PCT/GB97/01916 Sec. 371 Date Dec. 15, 1998 Sec. 102(e) Date Dec. 15, 1998 PCT Filed Jul. 15, 1997 PCT Pub. No. WO98/02568 PCT Pub. Date Jan. 22, 1998Process for obtaining an enantiomerically enriched N-acylazetidine-2-carboxylic acid, wherein a racemic N-acylazetidine-2-carboxylic acid ester is contacted with an enzyme that displays enantiospecificity to form enantiomerically enriched N-acylazetidine-2-carboxylic acid.