50439-45-7

Basic information

• Product Name: (2S,5R)-trans-5-Hydroxypiperidine-2-carboxylic acid
• Synonyms: (2S,5R)-trans-5-Hydroxypiperidine-2-carboxylic acid;(2S,5R)-5-Hydroxypipecolic acid;(2S,5R)-5-hydroxypiperidine-2-carboxylic acid
• CAS NO: 50439-45-7
• Molecular Formula: C₆H₁₁NO₃
• Molecular Weight: 145.16
• Mol File: 50439-45-7.mol

Chemical Properties

• Boiling Point: 354.8±42.0 °C(Predicted)
• Appearance: /
• Density: 1.299
• PKA: 2.31±0.40(Predicted)
• CAS DataBase Reference: (2S,5R)-trans-5-Hydroxypiperidine-2-carboxylic acid(CAS DataBase Reference)
• NIST Chemistry Reference: (2S,5R)-trans-5-Hydroxypiperidine-2-carboxylic acid(50439-45-7)
• EPA Substance Registry System: (2S,5R)-trans-5-Hydroxypiperidine-2-carboxylic acid(50439-45-7)

Safety Data

• Hazardous Substances Data: 50439-45-7(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(2S,5R)-trans-5-Hydroxypiperidine-2-carboxylic acid is used as a key component in the development of new drugs for the treatment of neurodegenerative diseases. Its specific biological and pharmacological properties make it a promising candidate for further study and potential therapeutic use in this field.

Upstream product

• 15069-92-8 5-hydroxypicolinic acid 
• 2219-28-5 δ-hydroxylysine hydrochloride 
• 504-91-6 2,6-diamino-5-hydroxy-hexanoic acid 
• 59182-85-3 benzyloxycarbonyl-L-baikiain 
• 3105-95-1 pipecolinic acid 
• 84409-89-2 (2S,5R)-N-[(benzyloxy)carbonyl]-5-hydroxy-2-piperidinecarboxylic acid 
• 13096-31-6 rac-(2R*,5S*)-5-hydroxypiperidine-2-carboxylic acid 

Downstream Products

• 84409-89-2 (2S,5R)-N-[(benzyloxy)carbonyl]-5-hydroxy-2-piperidinecarboxylic acid 
• 50439-45-7 (2S,5R)-5-hydroxy-2-piperidinecarboxylic acid 
• 138662-60-9 2R,5S-5-hydroxy-piperidine-2-carboxylic acid 
• 189952-46-3 (2S,5R)-methyl 5-hydroxypiperidine-2-carboxylate 
• 1487347-86-3 (2S,5R)-1-(tert-butoxycarbonyl)-5-hydroxypiperidine-2-carboxylic acid 

Relevant articles and documents

Development of a Stereoselective Synthesis of (1 R,4 R)- and (1 S,4 S)-2-Oxa-5-azabicyclo[2.2.2]octane

Despite the prevalence of morpholine derivatives and bridged heterocycles in medicinally relevant compounds, bridged bicyclic morpholines remain scarce because of the challenges associated with their synthesis. MRK A, an IDH1mut inhibitor for the treatment of glioma, derives its potency in part from substitution of a zigzag 2,5-bicyclic morpholine, 2-oxa-5-azabicyclo[2.2.2]octane, at C8. While existing entries suffered from low yields and lack of stereochemical control, we developed concise stereospecific routes toward both enantiomers of the zigzag morpholine antipode. The key common intermediate in the two routes was a chiral bicyclic lactone, which was readily synthesized following our previous synthesis of relebactam from optically pure (2S,5S)-5-hydroxypiperidine-2-carboxylic acid (HPA). The desired (R,R) enantiomer for incorporation into MRK A required inversion of both stereocenters of the bicyclic lactone intermediate, which was accomplished by epimerization via a crystallization-induced diastereomer transformation process followed by a key Ti(OiPr)4-mediated intramolecular SN2 ring closure. By this method, the (R,R)-zigzag morpholine was synthesized in six steps from HPA in 25% overall yield.

Studies on the selectivity of proline hydroxylases reveal new substrates including bicycles

Studies on the substrate selectivity of recombinant ferrous-iron- and 2-oxoglutarate-dependent proline hydroxylases (PHs) reveal that they can catalyse the production of dihydroxylated 5-, 6-, and 7-membered ring products, and can accept bicyclic substrates. Ring-substituted substrate analogues (such hydroxylated and fluorinated prolines) are accepted in some cases. The results highlight the considerable, as yet largely untapped, potential for amino acid hydroxylases and other 2OG oxygenases in biocatalysis.

METHOD FOR PRODUCING cis-5-HYDROXY-2-PIPERIDINECARBOXYLIC ACID DERIVATIVE, AND METHOD FOR PURIFYING cis-5-HYDROXY-2-PIPERIDINECARBOXYLIC ACID

The present invention aims to provide a method for purifying cis-5-hydroxy-2-piperidinecarboxylic acid with high purity, and a method for producing its derivative. The present invention provides a method for producing a cis-5-hydroxy-2-piperidinecarboxylic acid derivative, which method comprises a step of converting cis-5-hydroxy-2-piperidinecarboxylic acid into a compound(s) of Formula (1) and/or Formula (2) (wherein R1 represents a protective group for an amino group, and R2 represents a C1-C6 alkyl group), and a method for purifying cis-5-hydroxy-2-piperidinecarboxylic acid.

A simple procedure for selective hydroxylation of L -proline and l -pipecolic acid with recombinantly expressed proline hydroxylases

Due to their diverse regio- and stereoselectivities, proline hydroxylases provide a straightforward access to hydroxprolines and other hydroxylated cylic amino acids, valuable chiral building blocks for chemical synthesis, which are often not available at reasonable expense by classical chemical synthesis. As yet, the application of proline hydroxylases is limited to a sophisticated industrial process for the production of two hydroxyproline isomers. This is mainly due to difficulties in their heterologues expression, their limited in vitro stability and complex product purification procedures. Here we describe a facile method for the production of cis-3-, cis-4- and trans-4-proline hydroxylase, and their application for the regio- and stereoselective hydroxylation of L-proline and its six-membered ring homologue l-pipecolic acid. Since in vitro catalysis with these enzymes is not very efficient and conversions are restricted to the milligram scale, an in vivo procedure was established, which allowed a quantitative conversion of 6 mM l-proline in shake flask cultures. After facile product purification via ion exchange chromatography, hydroxyprolines were isolated in yields of 35-61% (175-305 mg per flask). L-Pipecolic acid was converted with the isolated enzymes to prove the selectivities of the reactions. In transformations with optimized iron(II) concentration, conversions of 17-68% to hydroxylated products were achieved. The regio- and stereochemistry of the products was determined by NMR techniques. To demonstrate the applicability of the preparative in vivo approach for non-physiological substrates, L-pipecolic acid was converted with an E. coli strain producing trans-4-proline hydroxylase to trans-5-hydroxy-L-pipecolic acid in 61% yield. Thus, a synthetically valuable group of biocatalysts was made readily accessible for application in the laboratory without a need for special equipment or considerable development effort.

Stereoselective preparation of cyclic l-amino acids

The invention concerns a method for producing a cyclic L-amino acid of formula (I), characterised in that it consists in reacting a L-diamino acid of formula (II) or an enantiomeric mixture comprising such a L-diamino acid and a corresponding D-diamino acid in variable proportions, in the presence of an ornithine cyclodeaminase or a polypeptide homologous to the ornithine cyclodeaminase. 1

Substrate selectivities of proline hydroxylases

Substrate selectivities of microbial proline 4-hydroxylase and proline 3-hydroxylases, all of which were purified from recombinant Escherichia coli, were investigated. L-2-Azetidine carboxylate, 3,4-dehydro-L-proline and L- pipecolinic acid were hydroxylated by those enzymes in regio- and stereospecific manner.

PREPARATION OF TRANS-5-HYDROXY-L-PIPECOLIC ACID AND CIS-4-HYDROXY-L-PIPECOLIC ACID FROM L-BAIKIAIN (1,2,5,6-L-TETRAHYDROPYRIDINE-2-CARBOXYLIC ACID).

Z-trans-5-OH-L-pipecolic acid together with Z-cis-4-OH-L-pipecolic acid is obtained in a 7:3 ratio by reduction of the oxymercuration product of Z-L-baikiain (Z-1,2,5,6-L-tetrahydropyridine-2-carboxylic acid).The opposite composition ratio is obtained using mercuric trifluoroacetate, thus giving access to the preparation of either of the two isomers.