13250-12-9

Usage

Uses

Used in Pharmaceutical Chemistry:
(R)-(-)-2-Aminobutane is used as a chiral auxiliary for [application reason] in the synthesis of various pharmaceutical compounds. Its ability to determine enantiomeric excess makes it a valuable tool in the development of enantiomerically pure drugs, which is crucial for ensuring the desired therapeutic effects and minimizing potential side effects.
Used in Organic Synthesis:
(R)-(-)-2-Aminobutane is used as a chiral auxiliary for [application reason] in the synthesis of complex organic molecules. Its stereochemistry can be exploited to control the stereoselectivity of various reactions, leading to the formation of desired enantiomers with high purity.
Used in the Synthesis of Aminodiphosphine Ligands:
(R)-(-)-2-Aminobutane is used as a substrate to prepare (R)-(?)-sec-butylbis(2-hydroxyethyl)amine, an intermediate for the synthesis of aminodiphosphine ligands. These ligands are important in homogeneous catalysis and can be used in various industrial applications, such as the production of fine chemicals and pharmaceuticals.
Used in the Study of Mitsunobu Reaction:
(R)-(-)-2-Aminobutane serves as a substrate to demonstrate the stereochemistry of the Mitsunobu reaction in the synthesis of secondary amines. Understanding the stereochemical outcome of this reaction is essential for the development of enantiomerically pure secondary amines, which are important building blocks in the synthesis of various biologically active compounds.
Used in the Study of Singlet-Triplet Transitions in Circular Dichroism:
(R)-(-)-2-Aminobutane acts as a model compound in the study of singlet-triplet transitions in circular dichroism. This research area is important for understanding the electronic structure of chiral molecules and can provide valuable insights into the development of new chiral materials and sensors.

Purification Methods

Dry it over solid NaOH overnight and fractionate it through a short helices packed column. The L-hydrogen tartrate salt has m 139-140o (from H2O), the 1H2O has m 96o []D +18.1o (c 11, H2O), the hydrochloride has m 152o [ ] 21 -1.1o (c 13, H2O) and the benzoyl derivative crystallises from EtOH as needles with m 97o, [] 21 -34.9o (c 11, H2O). [Bruck et al. J Chem Soc 921 1956,Kjaer & Hansen Acta Chem Scand 11 898 1957.] [Beilstein 4 H 161, 4 I 372, 4 III 308, 4 IV 617.] The S -(+)-enantiomer has has same properties except for the optical rotation which has the opposite sign.

InChI:InChI=1/C4H11N/c1-3-4(2)5/h4H,3,5H2,1-2H3/t4-/m0/s1

Upstream product

• 96-29-7 ethyl methyl ketone oxime 
• 131491-44-6 (S)-2-butyl azide 
• 98289-88-4 (R)-(-)-2-benzyloxycarbonylaminobutane 
• 33966-50-6 SEC-BUTYLAMINE 
• 141-78-6 ethyl acetate 
• 111-62-6 oleic acid ethyl ester 
• 106-32-1 octanoic acid ethyl ester 
• 110-38-3 decanoic acid ethyl ester 
• 627-90-7 ethyl undecanoate 
• 105-54-4 butanoic acid ethyl ester 
• 143-07-7 lauric acid 
• 952524-02-6 (S)-1-benzoyl-2-(α-acetoxyethyl)benzimidazole 
• 113-24-6 sodium pyruvate 
• 3852-09-3 methyl 3-methoxypropionate 

Downstream Products

• 25991-45-1 1-(R)-sec-butyl-piperidine 
• 129991-09-9 (R)-N-Boc-2-aminobutane 
• 110012-91-4 (R)-(+)-N-carbobenzoxy-2-<(1-methylpropyl)amino>ethylamine 
• 39076-02-3 ((R)-sec-Butyl)-carbamic acid methyl ester 
• 546120-59-6 (R)-N-((R)-sec-Butyl)-2-(4-chloro-2-methyl-phenoxy)-propionamide 
• 89840-66-4 ((1R)-1-methylpropyl)((2-nitrophenyl)sulfonyl)amine 
• 869307-60-8 N-benzyloxycarbonyl-(2S)-aminobutyryl-L-proline (R)-sec-butylamide 
• 63-91-2 L-phenylalanine 
• 673-06-3 D-(R)-phenylalanine 
• 556-02-5 tyrosine 
• 60-18-4 L-tyrosine 
• 59-92-7 levodopa 

Relevant academic research and scientific papers

Preparation of (R)-amines from racemic amines with an (S)-amine transaminase from Bacillus megaterium

Screening was carried out to identify strains useful for the preparation of (R)-1-cyclopropylethylamine and (R)-sec-butylamine by resolution of the racemic amines with an (S)-specific transaminase. Several Bacillus megaterium strains from our culture collection as well as several soil isolates were found to have the desired activity for the resolution of the racemic amines to give the (R)-enantiomers. Using an extract of the best strain, Bacillus megaterium SC6394, the reaction was shown to be a trans-amination requiring pyruvate as amino acceptor and pyridoxal phosphate as a cofactor. Initial batches of both amines were produced using whole cells of Bacillus megaterium SC6394. The transaminase was purified to homogeneity to obtain N-terminal as well as internal amino acid sequences. The sequences were used to design polymerase chain reaction (PCR) primers to enable cloning and expression of the trans-aminase in E. coli SC16578. In contrast to the original B. megaterium process, pH control and aeration were not required for the resolution of sec-butyl-amine and an excess of pyruvate was not consumed by the recombinant cells. The resolution of sec-butylamine (0.68M) using whole cells of E. coli SC16578 was scaled up to give (R)-sec-butylamine·1/2 H2SO 4 in 46.6% isolated yield with 99.2% ee. An alternative isolation procedure was also used to isolate (R)-secbutylamine as the free base.

Identification of novel thermostable ω-transaminase and its application for enzymatic synthesis of chiral amines at high temperature

A novel thermostable ω-transaminase from Thermomicrobium roseum which showed broad substrate specificity and high enantioselectivity was identified, expressed and biochemically characterized. The advantage of this enzyme to remove volatile inhibitory by-products was demonstrated by performing asymmetric synthesis and kinetic resolution at high temperature.

Enzymatic resolution of sec-butylamine

Resolution of (±)-sec-butylamine by Candida antarctica lipase provided a very low enantiomeric excess of the residual amine when either ethyl or vinyl butyrate was used as the acylating agent. The enantiomeric excess was increased by using ethyl esters of long chain fatty acids. The rate of the reaction was increased by using methyl t-butyl ether as a solvent. (S)-sec-Butylamine of very high enantiomeric excess was obtained by C. antarctica lipase catalyzed acylation with ethyl decanoate in methyl t-butyl ether.

Simultaneous Preparation of (S)-2-Aminobutane and d -Alanine or d -Homoalanine via Biocatalytic Transamination at High Substrate Concentration

(S)-2-Aminobutane, d-alanine, and d-homoalanine are important intermediates for the production of various active pharmaceutical ingredients and food additives. The preparation of these small chiral amine or amino acids with high water solubility still demands searching for efficient methods. In this work, we identified an ω-transaminase (ω-TA) from Sinirhodobacter hungdaonensis (ShdTA) that catalyzed the kinetic resolution of racemic 2-aminobutane at a concentration of 800 mM using pyruvate as the amino acceptor, leading to the simultaneous isolation of enantiopure (S)-2-aminobutane and d-alanine in 46% and 90% yield, respectively. In addition, (S)-2-aminobutane (98% ee) and d-homoalanine (99% ee) were isolated in 45% and 93% yield, respectively, in the kinetic resolution of racemic 2-aminobutane at a concentration of 400 mM coupled with deamination of l-threonine by threonine deaminase. We thus developed a biocatalytic process for the practical synthesis of these valuable small chiral amine and d-amino acids.

Ruthenium Catalyzed Direct Asymmetric Reductive Amination of Simple Aliphatic Ketones Using Ammonium Iodide and Hydrogen

The direct conversion of ketones into chiral primary amines is a key transformation in chemistry. Here, we present a ruthenium catalyzed asymmetric reductive amination (ARA) of purely aliphatic ketones with good yields and moderate enantioselectivity: up to 99 percent yield and 74 percent ee. The strategy involves [Ru(PPh3)3H(CO)Cl] in combination with the ligand (S,S)-f-binaphane as the catalyst, NH4I as the amine source and H2 as the reductant. This is a straightforward and user-friendly process to access industrially relevant chiral aliphatic primary amines. Although the enantioselectivity with this approach is only moderate, to the extent of our knowledge, the maximum ee of 74 percent achieved with this system is the highest reported till now apart from enzyme catalysis for the direct transformation of ketones into chiral aliphatic primary amines.

Separate Sets of Mutations Enhance Activity and Substrate Scope of Amine Dehydrogenase

Mutations were introduced into the leucine amine dehydrogenase (L-AmDH) derived from G. stearothermophilus leucine dehydrogenase (LeuDH) with the goals of increased activity and expanded substrate acceptance. A triple variant (L-AmDH-TV) including D32A, F101S, and C290V showed an average of 2.5-fold higher activity toward aliphatic ketones and an 8.0 °C increase in melting temperature. L-AmDH-TV did not show significant changes in relative activity for different substrates. In contrast, L39A, L39G, A112G, and T133G in varied combinations added to L-AmDH-TV changed the shape of the substrate binding pocket. L-AmDH-TV was not active on ketones larger than 2-hexanone. L39A and L39G enabled activity for straight-chain ketones as large as 2-decanone and in combination with A112G enabled activity toward longer branched ketones including 5-methyl-2-octanone.

Deracemization of Racemic Amines to Enantiopure (R)- and (S)-amines by Biocatalytic Cascade Employing ω-Transaminase and Amine Dehydrogenase

A one-pot deracemization strategy for α-chiral amines is reported involving an enantioselective deamination to the corresponding ketone followed by a stereoselective amination by enantiocomplementary biocatalysts. Notably, this cascade employing a ω-transaminase and amine dehydrogenase enabled the access to both (R)-and (S)-amine products, just by controlling the directions of the reactions catalyzed by them. A wide range of (R)-and (S)-amines was obtained with excellent conversions (>80 %) and enantiomeric excess (>99 % ee). Finally, preparative scale syntheses led to obtain enantiopure (R)- and (S)-13 with the isolated yields of 53 and 75 %, respectively.

(R)- SELECTIVE AMINATION

The present invention relates to a method for the enzymatic synthesis of enantiomerically enriched (R)-amines of general formula [1][c] from the corresponding ketones of the general formula [1][a] by using novel transaminases. These novel transaminases are selected from two different groups: either from a group of some 20 proteins with sequences as specified herein, or from a group of proteins having transaminase activity and isolated from a microorganism selected from the group of organisms consisting of Rahnella aquatilis, Ochrobactrum anthropi, Ochrobactrum tritici, Sinorhizobium morelense, Curtobacterium pusiffium, Paecilomyces lilacinus, Microbacterium ginsengisoli, Microbacterium trichothecenolyticum, Pseudomonas citronellolis, Yersinia kristensenii, Achromobacter spanius, Achromobacter insolitus, Mycobacterium fortuitum, Mycobacterium frederiksbergense, Mycobacterium sacrum, Mycobacterium fluoranthenivorans, Burkhoideria sp., Burkhoideria tropica, Cosmospora episphaeria, and Fusarium oxysporum.

The influence of conventional heating and microwave irradiation on the resolution of (RS)-sec-butylamine catalyzed by free or immobilized lipases

The lipases CAL-B, PSL, PSL-C, PSL-D, and A. niger lipase, free or immobilized in starch (obtained from two types of yam, known in Brazil as cara? (Discorea alata L.) and inhame (Colocasia esculenta (L.) Schott) or gelatin films, were used in the acylation of (RS)-sec-butylamine with different acyl donors in various organic solvents applying conventional heating (CH) or microwave (MW) irradiation. In the case of free A. niger lipase, the conversion degrees were three times higher using MW irradiation when compared to conventional heating at 35 °C. Using free A. niger lipase, the (R)-amide was obtained with a conversion degree of 21percent, resulting in eep > 99percent and E-value (enantioselectivity value) > 200, in 1 min of reaction under MW irradiation. When the A. niger lipase was immobilized in yam starch films, the (R)-amide was obtained in moderate conversions of 8-25percent after 3 or 5 min of reaction under MW irradiation, but with higher selectivity (eep > 99percent and E > 200) in comparison with the free form (conversion degree of 45percent, eep 81percent and E value of 18).

ω-Transaminase-catalyzed kinetic resolution of chiral amines using l-threonine as an amino acceptor precursor

Kinetic resolution of chiral amines using l-threonine as a cosubstrate was demonstrated by a biocatalytic strategy in which (S)-selective ω-transaminase (ω-TA) was coupled with threonine deaminase (TD), eliminating the need to use an expensive keto acid as an amino acceptor. The coupled enzyme reaction enabled simultaneous production of enantiopure (R)-amine and l-homoalanine which are pharmaceutically important building blocks. To extend the versatility of this strategy to production of both enantiomers of chiral amines, (R)-selective ω-TA coupled with TD was employed to produce (S)-amine.