1722-95-8

Usage

Uses

Chiral building block developed using Liverpool ChiroChem-patented technology.

InChI:InChI=1/C6H13N.ClH/c1-6-4-2-3-5-7-6;/h6-7H,2-5H2,1H3;1H/t6-;/m1./s1

Upstream product

• 109-05-7 2-Methylpiperidin 
• 1462-92-6 6-methyl-2,3,4,5-tetrahydro-pyridine 
• 5261-58-5 methylpentamethylenediamine 
• 505-18-0 2,3,4,5-tetrahydropyridine 
• 5119-88-0 (+)-(2R)-2-methylpiperidine hydrochloride 
• 1346682-05-0 C₁₆H₁₉NO₄ 
• 1346682-04-9 C₁₃H₁₃NO₄ 
• 1346682-03-8 (4aR,9aS)-4-[(3-mesitylpropanoyl)oxy]-4,4a,9,9a-tetrahydroindeno[2,1-b][1,4]oxazin-3(2H)-one 
• 155220-83-0 (3S,5R,8aR)-1-Benzyl-5-methyl-3-phenyl-octahydro-imidazo[1,2-a]pyridine 
• 348608-07-1 (+)-N-allyl,N-[(R)-α-methylbenzyl]-pent-1-ene-4-amine 
• 667870-42-0 (7aR,11R,13S)-11-(1H-benzotriazol-1-yl)-7a,8,10,11-tetrahydro-13-phenyl-9H,13H-naphtho[1,2-e]pyrido[2,1-b][1,3]oxazine 
• 500352-89-6 (7aR,13S)-13-phenyl-8,9,10,11-tetrahydro-7aH,13H-naphtho[1,2-e]pyrido[2,1-b][1,3]oxazine 
• 737760-86-0 (S)-4-isopropyl-3-(6-methylpyridin-2-yl)oxazolidin-2-one 
• 667870-56-6 1-[(S)-((R)-2-Methyl-piperidin-1-yl)-phenyl-methyl]-naphthalen-2-ol 

Downstream Products

• 873426-74-5 (R)-2-methyl-1-[(Z)-2-bromo-3-(3,4-dimethoxyphenyl)-prop-2-enyl]piperidine 
• 1394847-39-2 3-((R)-2-methylpiperidin-1-yl)-N-(4-((3-((S)-2-methylpiperidin-1-yl)propylamino)methyl)benzyl)propan-1-amine 
• 1394847-34-7 (R)-N,N'-(1,4-phenylenebis(methylene))bis(3-((R)-2-methylpiperidin-1-yl)propan-1-amine) 
• 873426-66-5 (R)-2-methyl-1-[(E)-3-(3,4-dimethoxyphenyl)-2-(4-methoxyphenyl)-prop-2-enyl]piperidine 

Relevant academic research and scientific papers

A practical preparation of (R)- and (S)-N-Boc-2-methylpiperidines

The resolution of (±)-2-methylpiperidine using D- and L-tartaric acid followed by direct conversion of the intermediate tartrate salts to (R) and (S)-N-Boc-2-methylpiperidine is described. Also described is an NMR protocol for assessing the optical purity of the intermediate tartrate salts as well as the free bases. The resolved enantiomers showed an ee of >98% based on NMR integration.

Stereoselective Biotransformations of Cyclic Imines in Recombinant Cells of Synechocystis sp. PCC 6803

Light-driven biotransformations in recombinant cyanobacteria allow to employ photosynthetic water-splitting for cofactor-regeneration and thus, to save the use of organic electron donors. The genes of three recombinant imine reductases (IREDs) were expressed in the cyanobacterium Synechocystis sp. PCC 6803 and eight cyclic imine substrates were screened in whole-cell biotransformations. While initial reactions showed low to moderate rates, optimization of the reaction conditions in combination with promoter engineering allowed to alleviate toxicity effects and achieve full conversion of prochiral imines with initial rates of up to 6.3 mM h?1. The high specific activity of up to 22 U gCDW ?1 demonstrates that recombinant cyanobacteria can provide large amounts of NADPH during whole cell reactions. The excellent optical purity of the products with up to >99 %ee underlines the usefulness of cyanobacteria for the stereoselective synthesis of amines.

Role of Methanol in Chiral Combinations of Host-Guest Molecules in the Inclusion Crystal: Structure Determination by X-Ray Crystallography

(S,S)-(-)-1,4-bisbenzene (2) and (S,S)-(-)-9,10-bisanthracene (3) include one enantiomer of racemic guest compound when the complexation is carried out in toluene, but include the other enantiomer and MeOH in a 1:1:1 ratio when the complexation is carried out in MeOH; the X-ray crystal structure of a 1:1:1 complex of 3, (S)-(+)-2-methylpiperidine and MeOH is reported, and preparation of the new chiral host compound (3) is also described.

Acylative kinetic resolution of racemic methyl-substituted cyclic alkylamines with 2,5-dioxopyrrolidin-1-yl (: R)-2-phenoxypropanoate

The diastereoselective acylation of a number of racemic methyl-substituted cyclic alkylamines with active esters of 2-phenoxypropanoic acid was studied in detail. The ester of (R)-2-phenoxypropanoic acid and N-hydroxysuccinimide was found to be the most selective agent. The highest stereoselectivity was observed in the kinetic resolution of racemic 2-methylpiperidine in toluene at -40 °C (selectivity factor s = 73) with the predominant formation of (R,R)-amide (93.7% de). To explain the observed stereoselectivity, DFT modelling of the transition states in the reactions of the title acylating agent with 2-methylpiperidine and 2-methylpyrrolidine was performed. The calculated values were in good agreement with experimental data. It has been demonstrated that the acylation proceeds via a concerted mechanism, in which the addition of an amine occurs simultaneously with the elimination of the hydroxysuccinimide fragment. The high stereoselectivity of the (R,R)-amide formation is largely ensured by the lower steric hindrances in the transition states as compared to the formation of (R,S)-amide.

Continuous Flow Chiral Amine Racemization Applied to Continuously Recirculating Dynamic Diastereomeric Crystallizations

A new, dynamic diastereomeric crystallization method has been developed, in which the mother liquors are continuously separated, racemized over a fixed-bed catalyst, and recirculated to the crystallizer in a resolution-racemization-recycle (R3) process. S

Synthesis of: N -heterocycles from diamines via H2-driven NADPH recycling in the presence of O2

Herein, we report an enzymatic cascade involving an oxidase, an imine reductase and a hydrogenase for the H2-driven synthesis of N-heterocycles. Variants of putrescine oxidase from Rhodococcus erythropolis with improved activity were identified. Substituted pyrrolidines and piperidines were obtained with up to 97% product formation in a one-pot reaction directly from the corresponding diamine substrates. The formation of up to 93% ee gave insights into the specificity and selectivity of the putrescine oxidase.

Sequence-Based In-silico Discovery, Characterisation, and Biocatalytic Application of a Set of Imine Reductases

Imine reductases (IREDs) have recently become a primary focus of research in biocatalysis, complementing other classes of amine-forming enzymes such as transaminases and amine dehydrogenases. Following in the footsteps of other research groups, we have established a set of IRED biocatalysts by sequence-based in silico enzyme discovery. In this study, we present basic characterisation data for these novel IREDs and explore their activity and stereoselectivity using a panel of structurally diverse cyclic imines as substrates. Specific activities of >1 U/mg and excellent stereoselectivities (ee>99 %) were observed in many cases, and the enzymes proved surprisingly tolerant towards elevated substrate loadings. Co-expression of the IREDs with an alcohol dehydrogenase for cofactor regeneration led to whole-cell biocatalysts capable of efficiently reducing imines at 100 mM initial concentration with no need for the addition of extracellular nicotinamide cofactor. Preparative biotransformations on gram scale using these ‘designer cells’ afforded chiral amines in good yield and excellent optical purity.

An (R)-imine reductase biocatalyst for the asymmetric reduction of cyclic imines

Although the range of biocatalysts available for the synthesis of enantiomerically pure chiral amines continues to expand, few existing methods provide access to secondary amines. To address this shortcoming, we have over-expressed the gene for an (R)-imine reductase [(R)-IRED] from Streptomyces sp. GF3587 in Escherichia coli to create a recombinant whole-cell biocatalyst for the asymmetric reduction of prochiral imines. The (R)-IRED was screened against a panel of cyclic imines and two iminium ions and was shown to possess high catalytic activity and enantioselectivity. Preparative-scale synthesis of the alkaloid (R)-coniine (90 % yield; 99 % ee) from the imine precursor was performed on a gram-scale. A homology model of the enzyme active site, based on the structure of a closely related (R)-IRED from Streptomyces kanamyceticus, was constructed and used to identify potential amino acids as targets for

Characterization of three novel enzymes with imine reductase activity

Imine reductases (IRED) are promising catalysts for the synthesis of optically pure secondary cyclic amines. Three novel IREDs from Paenibacillus elgii B69, Streptomyces ipomoeae 91-03 and Pseudomonas putida KT2440 were identified by amino acid or structural similarity search, cloned and recombinantly expressed in E. coli and their substrate scope was investigated. Besides the acceptance of cyclic amines, also acyclic amines could be identified as substrates for all IREDs. For the IRED from P. putida, a crystal structure (PDB-code 3L6D) is available in the database, but the function of the protein was not investigated so far. This enzyme showed the highest apparent E-value of approximately Eapp = 52 for (R)-methylpyrrolidine of the IREDs investigated in this study. Thus, an excellent enantiomeric purity of >99% and 97% conversion was reached in a biocatalytic reaction using resting cells after 24 h. Interestingly, a histidine residue could be confirmed as a catalytic residue by mutagenesis, but the residue is placed one turn aside compared to the formally known position of the catalytic Asp187 of Streptomyces kanamyceticus IRED.

Concerted amidation of activated esters: Reaction path and origins of selectivity in the kinetic resolution of cyclic amines via N-heterocyclic carbenes and hydroxamic acid cocatalyzed acyl transfer

The N-heterocyclic carbene and hydroxamic acid cocatalyzed kinetic resolution of cyclic amines generates enantioenriched amines and amides with selectivity factors up to 127. In this report, a quantum mechanical study of the reaction mechanism indicates that the selectivity-determining aminolysis step occurs via a novel concerted pathway in which the hydroxamic acid plays a key role in directing proton transfer from the incoming amine. This modality was found to be general in amide bond formation from a number of activated esters including those generated from HOBt and HOAt, reagents that are broadly used in peptide coupling. For the kinetic resolution, the proposed model accurately predicts the faster reacting enantiomer. A breakdown of the steric and electronic control elements shows that a gearing effect in the transition state is responsible for the observed selectivity.