327-56-0

Usage

Uses

Used in Pharmaceutical Industry:
D-Norleucine is used as a key intermediate in the synthesis of Thailandepsin B, a bicyclic depsipeptide histone deacetylase (HDAC) inhibitor. HDAC inhibitors have gained significant attention due to their potential as therapeutic agents for the treatment of various diseases, including cancer and neurodegenerative disorders. Thailandepsin B, in particular, has shown promising anticancer activity by modulating gene expression and inducing cell cycle arrest and apoptosis in cancer cells.
Additionally, D-Norleucine can be utilized in the development of other bioactive compounds and pharmaceuticals, given its unique structural features and potential for further functionalization. Its chiral nature allows for the exploration of novel stereoselective reactions and the synthesis of enantiomeric compounds with distinct biological activities.

Purification Methods

Crystallise norleucine from water or aqueous MeOH. [Huffman & Ingersoll J Am Chem Soc 73 3366 1951, Beilstein 4 III 1386, 4 IV 2628.]

InChI:InChI=1/C6H13NO2/c1-2-3-4-5(7)6(8)9/h5H,2-4,7H2,1H3,(H,8,9)/t5-/m1/s1

Upstream product

• 109-65-9 1-bromo-butane 
• 56-40-6 glycine 
• 91423-84-6 (2S)-2-bromohexanoic acid 
• 1927-36-2 (+)(R)-5-amino-hexen-⁽²⁾-oic acid-⁽⁶⁾ 
• 138261-25-3 (1'S,5R)-1-(benzyloxycarbonyl)-3-(1'-phenyleth-1'-yl)-5-butylimidazolidin-4-one 
• 119490-22-1 norleucine methyl ester 
• 616-06-8 2-amino-hexanoic acid 
• 88425-37-0 (R)-2-(N-(phenylsulfonyl)amino)-1-hexanol 
• 96864-08-3 <(1S,2R)-10-(N,N-dicyclohexylaminosulfonyl)born-2-yl> hexanoate 
• 104897-95-2 (S)-2-Bromo-hexanoic acid (1S,2R,4R)-1-[(dicyclohexylsulfamoyl)-methyl]-7,7-dimethyl-bicyclo[2.2.1]hept-2-yl ester 
• 27243-20-5 2-amino-hexanenitrile 
• 7732-18-5 water 
• 7664-41-7 ammonia 
• 118659-59-9 N-formyl-D-norleucine 

Downstream Products

• 43201-07-6 (R)-2-hydroxyhexanoic acid 
• 616-05-7 (R)-(+)-2-bromohexanoic acid 
• 80696-28-2 (2R)-2-amino-2-butyl-1-ethanol 
• 1221409-47-7 N-Phthaloyl-D-norleucine 
• 616-06-8 2-amino-hexanoic acid 
• 1554345-53-7 (R)-benzyl 2-(2-hydroxyhexanamido)acetate 
• 911481-41-9 C₈H₁₅NO₄ 
• 15027-14-2 (R)-(((benzyloxy)carbonyl)amino)-D-norleucine 
• 158741-04-9 (R)-2-amino-hexanol-⁽¹⁾; hydrochloride 
• 32653-33-1 (S)-α-Chlor-n-capronsaeure 
• 112883-41-7 (R)-((9H-fluoren-9-yl)methoxy)carbonyl-D-norleucine 
• 1043890-86-3 (R)-2-(4-fluoro-3,5-dimethylphenylamino)hexanoic acid tert-butoxyamide 
• 1043889-82-2 (R)-2-(4-fluoro-3,5-dimethylphenylamino)hexanoic acid hydroxyamide 

Relevant academic research and scientific papers

One-Pot Preparation of d-Amino Acids Through Biocatalytic Deracemization Using Alanine Dehydrogenase and Ω-Transaminase

d-Amino acids are pharmaceutically important building blocks, leading to a great deal of research efforts to develop cost-effective synthetic methods. Preparation of d-amino acids by deracemization has been conceptually attractive owing to facile synthesis of racemic amino acids by Strecker synthesis. Here, we demonstrated biocatalytic deracemization of aliphatic amino acids into d-enantiomers by running cascade reactions; (1) stereoinversion of l-amino acid to a d-form by amino acid dehydrogenase and ω-transaminase and (2) regeneration of NAD+ by NADH oxidase. Under the cascade reaction conditions containing 100?mM isopropylamine and 1?mM NAD+, complete deracemization of 100?mM dl-alanine was achieved after 24?h with 95% reaction yield of d-alanine (> 99% eeD, 52% isolation yield). Graphical Abstract: [Figure not available: see fulltext.].

Chemical Dynamic Thermodynamic Resolution and S/R Interconversion of Unprotected Unnatural Tailor-made α-Amino Acids

Described here is an advanced, general method for purely chemical dynamic thermodynamic resolution and S/R interconversion of unprotected tailor-made α-amino acids (α-AAs) through intermediate formation of the corresponding nickel(II)-chelated Schiff bases. The method features virtually complete stereochemical outcome, broad substrate generality (35 examples), and operationally convenient conditions allowing for large-scale preparation of the target α-AAs in enantiomerically pure form. Furthermore, the new type of nonracemizable axially chiral ligands can be quantitatively recycled and reused, rendering the whole process economically and synthetically attractive.

Deracemization of amino acids by coupling transaminases of opposite stereoselectivity

Biocatalytic deracemization of amino acids without relying on oxidase-based deamination of an unwanted enantiomer was demonstrated by coupling a-and w-transaminases displaying opposite stereoselectivity. This strategy employs isopropylamine and a keto acid as cosubstrates and is free of generation of hydrogen peroxide which is troublesome in the conventional oxidase-based methods.

A green and expedient synthesis of enantiopure diketopiperazines via enzymatic resolution of unnatural amino acids

Dipeptides comprising a d-phenylglycyl moiety coupled to the l-enantiomer of 2-amino butyric acid, norvaline, norleucine, and homocysteine were successfully synthesized from d-phenylglycine amide and the racemate of the corresponding unnatural amino acid.

SEPARATING AGENT FOR CHROMATOGRAPHY

A separating agent for chromatography is provided that is useful for the separation of specific compounds, e.g., for the optical resolution of amino acids. This separating agent for chromatography provides a higher productivity and contains a crown ether-like cyclic structure and optically active binaphthyl. This separating agent for chromatography containing a crown ether-like cyclic structure and optically active binaphthyl is provided by introducing a substitution group for binding to carrier into a specific commercially available 1,1′-binaphthyl derivative that has substituents at the 2, 2′, 3, and 3′ positions, then introducing a crown ether-like cyclic structure, and subsequently chemically bonding the binaphthyl derivative to the carrier through the substitution group for binding to carrier.

Characterization of d-amino acid aminotransferase from Lactobacillus salivarius

We searched a UniProt database of lactic acid bacteria in an effort to identify d-amino acid metabolizing enzymes other than alanine racemase. We found a d-amino acid aminotransferase (d-AAT) homologous gene (UniProt ID: Q1WRM6) in the genome of Lactobacillus salivarius. The gene was then expressed in Escherichia coli, and its product exhibited transaminase activity between d-alanine and α-ketoglutarate. This is the first characterization of a d-AAT from a lactic acid bacterium. L. salivarius d-AAT is a homodimer that uses pyridoxal-5′-phosphate (PLP) as a cofactor; it contains 0.91 molecules of PLP per subunit. Maximum activity was seen at a temperature of 60 °C and a pH of 6.0. However, the enzyme lost no activity when incubated for 30 min at 30 °C and pH 5.5 to 9.5, and retained half its activity when incubated at pH 4.5 or 11.0 under the same conditions. Double reciprocal plots of the initial velocity and d-alanine concentrations in the presence of several fixed concentrations of α-ketoglutarate gave a series of parallel lines, which is consistent with a Ping-Pong mechanism. The Km values for d-alanine and α-ketoglutarate were 1.05 and 3.78 mM, respectively. With this enzyme, d-allo-isoleucine exhibited greater relative activity than d-alanine as the amino donor, while α-ketobutylate, glyoxylate and indole-3-pyruvate were all more preferable amino acceptors than α-ketoglutarate. The substrate specificity of L. salivarius d-AAT thus differs greatly from those of the other d-AATs so far reported.

Chemical approach for interconversion of (S)- and (R)-α-amino acids

Here we report a general method for the preparation of unnatural (R)-α-amino acids via complexation of α-(phenyl)ethylamine derived chiral reagent (S)-3 with various (S)-α-amino acids. The reactions proceed with synthetically useful chemical yields and thermodynamically controlled diastereoselectivity. Chiral reagent (S)-3 can be conveniently recovered and reused without any loss of enantiomeric purity and reactivity. The Royal Society of Chemistry 2013.

Biocatalytic asymmetric synthesis of unnatural amino acids through the cascade transfer of amino groups from primary amines onto keto acids

Flee to the hills: An unfavorable equilibrium in the amino group transfer between amino acids and keto acids catalyzed by α-transaminases was successfully overcome by coupling with a ω-transaminase reaction as an equilibrium shifter, leading to efficient asymmetric synthesis of diverse unnatural amino acids, including L-tert-leucine and D-phenylglycine. Copyright

METHOD OF PRODUCING OPTICALLY ACTIVE AMINO ACID DERIVATIVE

The present application relates to a method for producing an optically active α-amino acid derivative, comprising steps of reacting an α-haloester derivative represented by the general formula (1): of which alcohol part of the ester group is an optically active alcohol derivative, with an amine compound; then deprotecting the obtained compound; further carrying out an ester exchange reaction. According to the present invention method, it is possible to easily produce an optically active α-amino acid ester derivative which is useful as an intermediate for drugs with high selectivity.