224321-05-5

Upstream product

• 147489-27-8 (2S)-4-oxo-1-phenylmethoxycarbonylpyrrolidine-2-carboxylic acid tert-butyl ester 
• 501-53-1 benzyl chloroformate 
• 13504-85-3 (2S,4R)-1-(benzyloxycarbonyl)-4-hydroxypyrrolidine-2-carboxylic acid 
• 64187-47-9 1-benzyloxycarbonyl-4-keto-L-proline 
• 71432-55-8 2-tert-butyl-1,3-diisopropylisourea 
• 13504-86-4 (2S,4S)-1-benzyloxycarbonyl-4-hydroxyproline 

Downstream Products

• 654666-08-7 (2S,4R)-4-(Benzenesulfonyl-cyano-methyl)-pyrrolidine-1,2-dicarboxylic acid 1-benzyl ester 2-tert-butyl ester 
• 322398-77-6 N-benzyloxycarbonyl-4-cis-mesyloxy-L-proline tert-butyl ester 
• 322398-79-8 N-benzyloxycarbonyl-4-trans-azido-L-proline tert-butyl ester 
• 322398-83-4 N-benzyloxycarbonyl-4-trans-amino-L-proline tert-butyl ester 
• 654666-12-3 (2S,4R)-4-(N-(2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl)-2-guanidinoethyl)-1-phenylmethoxycarbonyl-pyrrolidine-2-carboxylic acid 
• 654666-10-1 (2S,4R)-4-(N,N'-di-tert-butoxycarbonyl-2-guanidinoethyl)-1-phenylmethoxycarbonylpyrrolidine-2-carboxylic acid tert-butyl ester 
• 1026656-91-6 (2S,4R)-4-(2-Guanidino-ethyl)-pyrrolidine-1,2-dicarboxylic acid 1-benzyl ester 
• 654666-18-9 (2S,4R)-4-(2-Amino-ethyl)-pyrrolidine-1,2-dicarboxylic acid 1-benzyl ester 2-tert-butyl ester 
• 654666-09-8 (2S,4S)-4-cyanomethyl-1-phenylmethoxycarbonyl-pyrrolidine-2-carboxylic acid tert-butyl ester 

Relevant academic research and scientific papers

INHIBITORS OF SERINE PROTEASES, PARTICULARLY HCV NS3-NS4A PROTEASE

The present invention relates to compounds that inhibit serine protease activity, particularly the activity of hepatitis C virus NS3-NS4A protease. As such, they act by interfering with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The invention further relates to compositions comprising these compounds either for ex vivo use for administration to a patient suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a patient by administering a composition comprising a compound of this invention. The invention further relates to processes for preparing these compounds.

Restriction of a Peptide Turn Conformation and Conformational Analysis of Guanidino Group Using Arginine-Proline Fused Amino Acids: Application to Mini Atrial Natriuretic Peptide on Binding to the Receptor

Compounds (2S,4S)- and (2S,4R)-4-(2′-guanidinoethyl)proline have been synthesized as a conformationally restricted arginine, Their backbones fit the i + 1 position in a turn, and the side chains are restricted compared to that of arginine. These analogues were incorporated into mini atrial natriuretic polypeptide, which has an important turnlike conformation at Gly6-Arg7-Met8-Asp9. Structural analysis revealed that the size of the conformational space of Arg7 on binding to the receptor was approximately one-third of the entire conformational space.

The synthesis of isomeric 4-prolinylamines and 4,4′-diprolinylamines

Starting from the previously described tert-butyl esters of 4-epimeric N-benzyloxycarbonyl-4-hydroxyprolines and N-benzyloxycarbonyl-4-trans- and 4-cis-trifluoroacetaminoproline tert-butyl esters, the corresponding unprotected 4-aminoprolines and a number of their partially protected derivatives were synthesized via the intermediate 4-O-mesyl and 4-azide derivatives. The reductive animation of N-benzyloxycarbonyl-4-oxoproline tert-butyl ester with ammonium acetate led to N-benzyloxycarbonyl-4-cis-4′-cis- and 4-cis-4′-trans-diprolinylamines. The 1H NMR and CD spectra of the synthesized compounds are described.

The synthesis of bicyclic proline derivatives with 1,4N-lactam grouping

The N-benzyloxycarbonyl-4-oxoproline ferr-butyl ester prepared from trans-4-hydroxy-L-proline was shown to be capable of a reductive amination with esters of α- or β-amino acids to the corresponding (45)-4-aminoderivatives. One of the resulting products, (45)-4-glycinoderivative, was easily cyclized after selective removal of the acid-labile protective group. There resulted bridge bicyclic synthons suitable for peptide synthesis: (2S,5S)-benzyloxycarbonyl-4-methoxycarbonylmethyl-3-oxo-1,4-diazabicyclo[2.2.1] heptane, (2S,5S)-1-(9-fluorenylmethoxycarbonyl-4-methoxycarbonyl-3-oxo-1,4- diazabicyclo[2.2.1 ]heptane, and (2S,5S)-1-(9-fluorenylmethoxycarbonyl-4-carboxymethyl-3-oxo-l,4-diazabicyclo[2. 2.1]heptane. Their possible use for the study of biologically significant conformations of bioactive proline-containing oligopeptides is discussed.

Synthesis of conformationally constrained DTPA analogues. Incorporation of the ethylenediamine units as aminopyrrolidines

The synthesis of conformationally constrained diethylenetriaminepentaacetic acid (DTPA) analogues is an effort to probe the relationship between ligand structure and metal complex stability. In the pursuit of this objective, diastereomerically and enantiomerically pure mono- and bis-pyrrolidine analogues of DTPA have been prepared from trans-4-hydroxy-L-proline. The mono-pyrrolidine chelator 1 was constructed from a single hydroxyproline unit and an ethylenediamine moiety while two hydroxyproline-derived fragments 4e or 14b and 9b were coupled by N-alkylation of a triflate to afford the core bis-pyrrolidine structures: optically active 10 and meso-15. Deprotection of the triamine pentaesters 12 and 17 afforded the triamine pentaacetic acids 2 and 3 as their hydrochloride salts. The stereochemical homogeneity of precursor esters 12 and 17 was determined by HPLC using authentic epimeric standards to establish that essentially no racemization of the original amino acid α-center had occurred. Some loss of stereochemical homogeniety was encountered in the synthesis of 10 and 15 by N-alkylation of aminoproline 9b with a hydroxyproline-derived triflate, which had proceeded with some retention of configuration. The diastereomeric impurities were removed by crystallization of the respective benzyl carbamates. Bis-pyrrolidine pentaacids 2 and 3 formed isolable chelates with gadolinium and lutetium. A comparision of the lutetium chelates of 2 and 3 by NMR revealed significant differences which were reflective of a rigid structure with 2, while metal complexation with 3 was structurally less defined.