103201-78-1

Basic information

• Product Name: trans-4-Cyclohexyl-L-proline
• Synonyms: L-Proline, 4-cyclohexyl-, (4S)-;H-Chpro-OH;TRANS-4-CYCLOHEXYL-L-PROLINE (FOSINOPRIL''S INTERMEDIATE 2);trans-4-Cyclohexyl-L-proline;Fosinopril Intermediate 2;(2S,4S)-4-cyclohexylpyrrolidine-2-carboxylic acid;(4S)- 4-cyclohexyl-L-Proline
• CAS NO: 103201-78-1
• Molecular Formula: C₁₁H₁₉NO₂
• Molecular Weight: 197.28
• EINECS: 1806241-263-5
• Mol File: 103201-78-1.mol

Chemical Properties

• Melting Point: 260-262 °C(Solv: methanol (67-56-1); ethyl ether (60-29-7))
• Boiling Point: 343.919 °C at 760 mmHg
• Flash Point: 161.797 °C
• Appearance: /
• Density: 1.114 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.517
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• PKA: 2.35±0.40(Predicted)
• CAS DataBase Reference: trans-4-Cyclohexyl-L-proline(CAS DataBase Reference)
• NIST Chemistry Reference: trans-4-Cyclohexyl-L-proline(103201-78-1)
• EPA Substance Registry System: trans-4-Cyclohexyl-L-proline(103201-78-1)

Safety Data

• Hazardous Substances Data: 103201-78-1(Hazardous Substances Data)

Usage

Uses

Used in Medicinal Chemistry Research:
Trans-4-Cyclohexyl-L-proline is utilized as a key component in peptide synthesis for its ability to alter peptide conformation and enhance stability. Its unique structural properties make it an invaluable tool for studying protein folding and conformation, which are critical for understanding and developing new therapeutic agents.
Used in Drug Development:
In the pharmaceutical industry, trans-4-Cyclohexyl-L-proline serves as a building block for the design of novel drugs. Its incorporation into peptide-based drugs can potentially improve their efficacy and selectivity by modulating their interaction with target proteins, thus offering new avenues for the treatment of various diseases.
Used in Protein Engineering:
Trans-4-Cyclohexyl-L-proline is employed as a non-standard amino acid in protein engineering to create proteins with altered functions or improved properties. This can lead to the development of proteins with enhanced stability, increased solubility, or novel binding characteristics, which are essential for various biotechnological and therapeutic applications.
Used in Peptide Conformation Studies:
Researchers studying the relationship between peptide conformation and biological activity often use trans-4-Cyclohexyl-L-proline to probe and manipulate the structure of peptides. Its rigid and complex structure allows for the investigation of how specific conformational changes can affect peptide function and interactions with other biomolecules.
Overall, trans-4-Cyclohexyl-L-proline is a versatile synthetic amino acid with a wide range of applications in the fields of medicinal chemistry, drug development, protein engineering, and peptide conformation studies, making it an important compound for advancing our understanding of protein structure and function.

InChI:InChI=1/C11H19NO2/c13-11(14)10-6-9(7-12-10)8-4-2-1-3-5-8/h8-10,12H,1-7H2,(H,13,14)/t9-,10+/m1/s1

Upstream product

• 103201-84-9 (2S,4S)-4-Cyclohexyl-pyrrolidine-1,2-dicarboxylic acid 1-benzyl ester 
• 438492-63-8 benzyl trans-4-cyclohexyl-5-thio-N-benzyl-L-pyroglutamate 
• 38854-94-3 N-benzyl-L-pyroglutamic acid 
• 1521-51-3 rac-3-bromocyclohexene 
• 17342-08-4 (S)-Pyroglutaminol 
• 55629-96-4 ethyl 4-phenyl-2-oxobut-3-enoate 
• 120851-71-0 (2S,4S)-1-Benzoyl-4-phenyl-pyrrolidine-2-carboxylic acid 
• 96314-26-0 trans-4-phenyl-L-proline 
• 31560-20-0 (2S,4R)-1-benzoyl-4-hydroxypyrrolidine-2-carboxylic acid methyl ester 
• 103201-83-8 (2S-trans)-1-[(benzyloxy)carbonyl]-4-cyclohexyl-2-pyrrolidinemethanol 
• 103201-80-5 (3R,6S)-6-Cyclohex-2-enyl-3-phenyl-tetrahydro-pyrrolo[1,2-c]oxazol-5-one 
• 103201-81-6 ((2S,4S)-1-Benzyl-4-cyclohex-2-enyl-pyrrolidin-2-yl)-methanol 
• 103201-82-7 trans-4-cyclohexyl-L-prolinol 
• 438492-62-7 (2S,4S)-1-Benzyl-4-cyclohexyl-5-oxo-pyrrolidine-2-carboxylic acid benzyl ester 

Downstream Products

• 1356446-78-0 fosinopril 
• 95399-71-6 Fosinoprilat 

Relevant articles and documents

Preparation methods of antihypertensive Fosinopril sodium and key intermediate thereof

The invention relates to preparation methods of an antihypertensive Fosinopril sodium and a key intermediate thereof trans-4-phenyl-L-proline suitable for industrial production. Synthesis of the key intermediate trans-4-phenyl-L-proline has high chiral selectivity, and the method is simple and easy to operate.

A practical synthesis of optically active δ-nitro-α-ketoesters and 4-cyclohexyl-proline catalyzed by chiral squamides

Inexpensive and readily available squamides derived from 9-amino-9-deoxyepiquinine or 9-amino-9-deoxyepiquinidine were found to be superior catalysts for the asymmetric conjugate additions of t-butyl nitroacetate to β,γ-unsaturated-α-ketoesters. After the subsequent decarboxylation with silica gel, a variety of δ-nitro-α-ketoesters were obtained in good yields and with excellent enantioselectivities. The products were further transformed into ethyl 4-aryl-prolinate via a cascade nitro reduction and amination. A new synthesis of (2S,4S)-4-cyclohexyl-proline was also developed. A practical synthesis of optically active δ-nitro-α-ketoesters and 4-aryl-proline derivatives is described.

A convenient method for synthesis of trans-4-cyclohexyl-L-proline

A convenient method for the synthesis of the fosinopril precursor, trans-4-cyclohexyl-L-proline 1, has been developed. A highly stereoselective alkylation of N-benzyl-pyroglutamic acid 2 with 3-bromocyclohexene at -10°C and subsequent hydrogenolysis affor

Conversion of L-Pyroglutamic Acid to 4-Alkyl-Substituted L-Prolines. The Synthesis of trans-4-Cyclohexyl-L-proline

(S)-5-(Hydroxymethyl)-2-pyrrolidinone (3), prepared from L-pyroglutamic acid, was condensed with benzaldehyde to obtain the O,N-acetal 4 in excellent yield.Alkylation of 4 with 3-bromocyclohexene followed by reduction gave trans-4-cyclohexyl-L-prolinol (7) in good chemical yield with excellent stereoselectivity.Sequential N-protection, oxidation of the alcohol to the acid, and N-deprotection furnished trans-4-cyclohexyl-L-proline (1) in excellent yield and quality.Compound 1 serves as an intermediate for the preparation of ACE inhibitors including Fosenopril.