2187-07-7

Usage

InChI:InChI=1/C8H17NO2/c1-2-3-4-5-6-7(9)8(10)11/h7H,2-6,9H2,1H3,(H,10,11)/t7-/m1/s1

Upstream product

• 74-90-8 hydrogen cyanide 
• 40899-00-1 1-amino-heptan-1-ol 
• 880141-72-0 2-formylamino-octanoic acid 
• 2623-82-7 2-bromooctanoic acid 
• 3974-36-5 2-n-hexyl malonic acid 
• 5463-91-2 acetylamino-hexyl-malonic acid diethyl ester 
• 99310-52-8 (5-ethyl-[2]thienyl)-amino-acetic acid 
• 138286-80-3 Ethyl N-(trichloroacetyl)-2-aminooctanoate 
• 7647-01-0 hydrogenchloride 
• 10035-10-6 hydrogen bromide 
• 111-83-1 1-bromo-octane 
• 1068-90-2 2-acetylaminomalonic acid diethyl ester 
• 111-25-1 1-bromo-hexane 
• 26526-76-1 ethyl 2-cyanooctanoate 

Downstream Products

• 6271-04-1 4-hexyl-oxazolidine-2,5-dione 
• 761343-79-7 α-hexylglycine ethyl ester 
• 106819-03-8 (R)-α-aminooctanoic acid 
• 116783-26-7 (S)-α-aminooctanoic acid 
• 92211-95-5 2-((tertbutoxycarbonyl)amino)octanoic acid 
• 51714-09-1 3-acetamidononan-2-one 
• 328-51-8 2-oxooctanoic acid 
• 92211-96-6 N-tert-butoxycarbonyl-D-2-aminooctanoic acid 
• 5440-37-9 (R)-2-acetylamino-octanoic acid 

Relevant academic research and scientific papers

New Aspercryptins, Lipopeptide Natural Products, Revealed by HDAC Inhibition in Aspergillus nidulans

Unlocking the biochemical stores of fungi is key for developing future pharmaceuticals. Through reduced expression of a critical histone deacetylase in Aspergillus nidulans, increases of up to 100-fold were observed in the levels of 15 new aspercryptins, recently described lipopeptides with two noncanonical amino acids derived from octanoic and dodecanoic acids. In addition to two NMR-verified structures, MS/MS networking helped uncover an additional 13 aspercryptins. The aspercryptins break the conventional structural orientation of lipopeptides and appear "backward" when compared to known compounds of this class. We have also confirmed the 14-gene aspercryptin biosynthetic gene cluster, which encodes two fatty acid synthases and several enzymes to convert saturated octanoic and dodecanoic acid to α-amino acids.

Hexyl-modified morpholine-2,5-dione-based oligodepsipeptides with relatively low glass transition temperature

Oligodepsipeptides (oDPs), alternating copolymers of an α-amino acid and an α-hydroxy acid, are typically created by ring-opening polymerization (ROP) of morpholine-2,5-dione derivatives (MDs). In general, oDPs exhibit relatively high glass transition temperatures (Tgs) caused by the strong intermolecular H-bonding between amide and ester bonds. So far, it was not reported that variation at α-amino acid moieties in MDs monomers lead to lower Tg. Here we explored whether the thermal properties of the oDPs can be adjusted by introducing a hexyl side chain in the α-hydroxy acid part of the MDs. By synthesizing a MD with an atactic pendant hexyl group at position 3, the influence of a modification at position 6 compared to a modification at position 3 towards ROP was investigated. In both cases the atactic bulky side groups hindered the H-bonding between chain segments resulting in a significant reduction of the Tgs to a temperature around human body temperature (32 and 36 °C) in contrast to ROP of a MD providing a methyl group at position 3 and a Tg ≈ 65 °C. Such oDPs could be interesting candidate materials for biomedical applications such as degradable implants.

Semi-rational hinge engineering: modulating the conformational transformation of glutamate dehydrogenase for enhanced reductive amination activity towards non-natural substrates

The active site is the common hotspot for rational and semi-rational enzyme activity engineering. However, the active site represents only a small portion of the whole enzyme. Identifying more hotspots other than the active site for enzyme activity engineering should aid in the development of biocatalysts with better catalytic performance. Glutamate dehydrogenases (GluDHs) are promising and environmentally benign biocatalysts for the synthesis of valuable chirall-amino acids by asymmetric reductive amination of α-keto acids. GluDHs contain an inter-domain hinge structure that facilitates dynamic reorientations of the domains relative to each other. Such hinge-bending conformational motions of GluDHs play an important role in regulating the catalytic activity. Thus, the hinge region represents a potential hotspot for catalytic activity engineering for GluDHs. Herein, we report semi-rational activity engineering of GluDHs with the hinge region as the hotspot. Mutants exhibiting significantly improved catalytic activity toward several non-natural substrates were identified and the highest activity increase reached 104-fold. Molecular dynamics simulations revealed that enhanced catalytic activity may arise from improving the open/closed conformational transformation efficiency of the protein with hinge engineering. In the batch production of three valuablel-amino acids, the mutants exhibited significantly improved catalytic efficiency, highlighting their industrial potential. Moreover, the catalytic activity of several active site tailored GluDHs was also increased by hinge engineering, indicating that hinge and active site engineering are compatible. The results show that the hinge region is a promising hotspot for activity engineering of GluDHs and provides a potent alternative for developing high-performance biocatalysts toward chirall-amino acid production.

Preparative Asymmetric Synthesis of Canonical and Non-canonical a-amino Acids through Formal Enantioselective Biocatalytic Amination of Carboxylic Acids

Chemical and biocatalytic synthesis of non-canonical a-amino acids (ncAAs) from renewable feedstocks and using mild reaction conditions has not efficiently been solved. Here, we show the development of a three-step, scalable and modular one-pot biocascade for linear conversion of renewable fatty acids (FAs) into enantiopure l-a-amino acids. In module 1, selective a-hydroxylation of FAs is catalyzed by the P450 peroxygenase P450CLA. By using an automated H2O2 supplementation system, efficient conversion (46 to >99%; TTN>3300) of a broad range of FAs (C6:0 to C16:0) into valuable a-hydroxy acids (a-HAs; >90% a-selective) is shown on preparative scale (up to 2.3 gL1 isolated product). In module 2, a redox-neutral hydrogen borrowing cascade (alcohol dehydrogenase/amino acid dehydrogenase) allowed further conversion of a-HAs into l-a-AAs (20 to 99%). Enantiopure l-a-AAs (e.e. >99%) including the pharma synthon l-homo-phenylalanine can be obtained at product titers of up to 2.5 gL1. Based on renewables and excellent atom economy, this biocascade is among the shortest and greenest synthetic routes to structurally diverse and industrially relevant ncAAs.

Combinatorial Mutation Analysis of ω-Transaminase to Create an Engineered Variant Capable of Asymmetric Amination of Isobutyrophenone

ω-Transaminase (ω-TA) is an important enzyme for asymmetric synthesis of chiral amines. Rapid creation of a desirable ω-TA variant, readily available for scalable process operation, is demanded and has attracted intense research efforts. In this study, we aimed to develop a quantitative mutational analysis (i. e., R-analysis) that enables prediction of combinatorial mutation outcomes and thereby provides reliable guidance of enzyme engineering through combination of already characterized mutations. To this end, we determined three mutatable active-site residues of ω-TA from Ochrobactrum anthropi (i. e., leucine 57, tryptophan 58 and valine 154) by examining activities of nine alanine-scanning mutants for seven substrate pairs. The R-analysis of the mutatable residues is based on assessment of changes in relative activities for a series of structurally analogous substrates. Using three sets of substrates (five α-keto acids, six arylalkylamines and three arylalkyl ketones), we found that combination of two point mutations display additive effects of each mutational outcome such as steric relaxation for bulky substrates or catalytic enhancement for amination of ketones. Consistent with the R-analysis-based prediction, the ω-TA variant harboring triple alanine mutations, i. e. L57A, W58A and V154A, showed high activity improvements for bulky substrates, e. g. a 3.2×104-fold activity increase for 1-phenylbutylamine. The triple mutant even enabled asymmetric amination of isobutyrophenone, carrying a branched-chain alkyl substituent to be accepted in a small binding pocket that normally shows a steric limit up to an ethyl group, with >99% ee of a resulting (S)-amine. (Figure presented.).

Preparative Asymmetric Synthesis of Canonical and Non-canonical α-amino Acids Through Formal Enantioselective Biocatalytic Amination of Carboxylic Acids

Chemical and biocatalytic synthesis of non-canonical α-amino acids (ncAAs) from renewable feedstocks and using mild reaction conditions has not efficiently been solved. Here, we show the development of a three-step, scalable and modular one-pot biocascade for linear conversion of renewable fatty acids (FAs) into enantiopure l-α-amino acids. In module 1, selective α-hydroxylation of FAs is catalyzed by the P450 peroxygenase P450CLA. By using an automated H2O2 supplementation system, efficient conversion (46 to >99%; TTN>3300) of a broad range of FAs (C6:0 to C16:0) into valuable α-hydroxy acids (α-HAs; >90% α-selective) is shown on preparative scale (up to 2.3 g L?1 isolated product). In module 2, a redox-neutral hydrogen borrowing cascade (alcohol dehydrogenase/amino acid dehydrogenase) allowed further conversion of α-HAs into l-α-AAs (20 to 99%). Enantiopure l-α-AAs (e.e. >99%) including the pharma synthon l-homo-phenylalanine can be obtained at product titers of up to 2.5 g L?1. Based on renewables and excellent atom economy, this biocascade is among the shortest and greenest synthetic routes to structurally diverse and industrially relevant ncAAs. (Figure presented.).

Asymmetric Transamination of α-Keto Acids Catalyzed by Chiral Pyridoxamines

A new type of novel chiral pyridoxamines 3a-g containing a side chain has been developed. The pyridoxamines displayed catalytic activity and promising enantioselectivity in biomimetic asymmetric transamination of α-keto acids, to give various α-amino acids in 47-90% yields with up to 87% ee's under very mild conditions. An interesting effect of the side chain on enantioselectivity was observed in the reaction.

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.

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

ω-Transaminase-catalyzed asymmetric synthesis of unnatural amino acids using isopropylamine as an amino donor

Isopropylamine is an ideal amino donor for reductive amination of carbonyl compounds by ω-transaminase (ω-TA) owing to its cheapness and high volatility of a ketone product. Here we developed asymmetric synthesis of unnatural amino acids via ω-TA-catalyzed amino group transfer between α-keto acids and isopropylamine.