587887-98-7

Upstream product

• 87691-27-8 N-tert-butoxycarbonyl-L-cis-4-hydroxyproline 
• 100-39-0 benzyl bromide 
• 203866-14-2 (2S,4R)-1-[(tert-butoxy)carbonyl]-4-fluoropyrrolidine-2-carboxylic acid 
• 89813-47-8 N-(tert-butoxycarbonyl)-(2S,4R)-4-hydroxyproline benzyl ester 
• 132622-90-3 (2S,4S)-2-benzyl 1-tert-butyl 4-hydroxypyrrolidine-1,2-dicarboxylate 
• 67-56-1 methanol 
• 481704-22-7 (2R,4S)-2-benzyl 1-tert-butyl 4-hydroxypyrrolidine-1,2-dicarboxylate 
• 74844-91-0 (2S,4S)-N-tert-butoxycarbonyl-4-hydroxyproline methyl ester 

Downstream Products

• 587888-01-5 N-[N-[N-(tert-butoxycarbonyl)-(2S,4R)-4-fluoroprolyl]-2S-prolyl]-glycine benzyl ester 
• 870992-72-6 N-9-fluorenylmethoxycarbonyl-(2S,4S)-4-fluoroprolyl-(2S,4R)-4-fluoroprolylglycine benzyl ester 
• 870992-74-8 N-9-fluorenylmethoxycarbonyl-(2S,3S)-3-fluoroprolyl-(2S,4R)-4-fluoroprolylglycine benzyl ester 
• 870992-70-4 N-tert-butoxycarbonyl-(2S,4R)-4-fluoroprolylglycine benzyl ester 
• 203866-14-2 (2S,4R)-1-[(tert-butoxy)carbonyl]-4-fluoropyrrolidine-2-carboxylic acid 

Relevant academic research and scientific papers

Cyclic Peptide Mimetic of Damaged Collagen

Collagen is the most abundant protein in humans and the major component of human skin. Collagen mimetic peptides (CMPs) can anneal to damaged collagen in vitro and in vivo. A duplex of CMPs was envisioned as a macromolecular mimic for damaged collagen. The duplex was synthesized on a solid support from the amino groups of a lysine residue and by using olefin metathesis to link the N termini. The resulting cyclic peptide, which is a monomer in solution, binds to CMPs to form a triple helix. Among these, CMPs that are engineered to avoid the formation of homotrimers but preorganized to adopt the conformation of a collagen strand exhibit enhanced association. Thus, this cyclic peptide enables the assessment of CMPs for utility in annealing to damaged collagen. Such CMPs have potential use in the diagnosis and treatment of fibrotic diseases and wounds.

SUBSTITUTED PYRROLIZINE COMPOUNDS AND USES THEREOF

This application relates to substituted fused pyrrole compounds of formula I, and pharmaceutical compositions comprising them which inhibit HBV replication, and methods of making and using them. Formula (I)

Incorporation of fluoroprolines to proctolin: Study on the effect of a fluorine atom toward peptidic conformation

In spite of quite small steric perturbation, substitution of proline (Pro) in the target pentapeptide proctolin (Arg-Tyr-Leu-Pro-Thr) for (4R)- as well as (4S)-4-fluoroproline led to apparent alteration of the pyrrolidine ring structure which eventually r

Stereoelectronic and steric effects in the collagen triple helix: Toward a code for strand association

Collagen is the most abundant protein in animals. The protein consists of a helix of three strands, each with sequence X-Y-Gly. Natural collagen is most stable when X is (2S)-proline (Pro) and Y is (2S,4R)-4-hydroxyproline (4R-Hyp). We had shown previously that triple helices in which X is (2S,4S)-4- fluoroproline (4S-Flp) or Y is (2S,4R)-4-fluoroproline (4R-Flp) display hyperstability. This hyperstability arises from stereoelectronic effects that preorganize the main-chain dihedral angles in the conformation found in the triple helix. Here, we report the synthesis of strands containing both 4S-Flp in the X-position and 4R-Flp in the Y-position. We find that these strands do not form a stable triple helix, presumably because of an unfavorable steric interaction between fluoro groups on adjacent strands. Density functional theory calculations indicate that (2S,3S)-3-fluoroproline (3S-Flp), like 4S-Flp, should preorganize the main chain properly for triple-helix formation but without a steric conflict. Synthetic strands containing 3S-Flp in the X-position and 4R-Flp in the Y-position do form a triple helix. This helix is, however, less stable than one with Pro in the X-position, presumably because of an unfavorable inductive effect that diminishes the strength of the interstrand 3S-FlpC=O...H-NGly hydrogen bond. Thus, other forces can counter the benefits derived from the proper preorganization. Although (Pro-Pro-Gly) 7 and (4S-Flp-4R-Flp-Gly)7 do not form stable homotrimeric helices, mixtures of these two peptides form stable heterotrimeric helices containing one (Pro-Pro-Gly)7 strand and two (4S-Flp-4R-Flp-Gly) 7 strands. This stoichiometry can be understood by considering the cross sections of the two possible heterotrimeric helices. This unexpected finding portends the development of a "code" for the self-assembly of determinate triple helices from two or three strands.

Collagen mimics

A novel collagen mimic comprising a tripeptide unit having the formula (flpYaaGly)n, where flp is 4(S)-fluoro-L-proline, is disclosed. The collagen mimic has increased stability relative to the collagen-related triple helices (ProYaaGly)n

Fluorinating reactants and process for their preparation

alpha,alpha-Difluoroalkylamines (I) are new. Also new are mixtures (A) containing (a) a broader class of alpha,alpha-difluoroalkylamines (I'), (b) an aprotic tertiary amine having no fluoro atoms in the alpha-position relative to nitrogen and/or a N-heteroaromatic compound and (c) hydrogen fluoride; and some specific dichloro compound intermediates. alpha,alpha-Difluoroalkylamines of formula R1-CF2-NR2R3 (I) are new. R1 = H, 1-12C alkyl, ((2-12C) alkylene-O)n-(1-12C) alkyl, 4-15C aralkyl or 3-14C heteroaryl; n = 1-5; R2, R3 = 4-15C aralkyl or 1-12C alkyl; or R2 + R3 or R1 + R2 and/or R3 = group completing a 3-12C cyclic group; the compounds 1,1-difluoromethyl-N,N-dimethylamine, 1,1-difluoromethyl-N,N-diethylamine, 1,1-difluoromethyl-N,N-diisopropylamine and 1,1-difluoro-N,N-2-trimethyl-1-propanamine are excluded. Independent claims are included for: (a) new mixtures (A) comprising (a) alpha,alpha-difluoroalkylamines of formula R4-CF2-NR5R6 (I'), (b) at least one aprotic tertiary amine having no fluoro atoms in the alpha-position relative to the nitrogen and/or at least one N-heteroaromatic compound and (c) hydrogen fluoride; (b) the preparation of (I) and (A); and (c) the following new geminal dichloro compound intermediates: 1,1-dichloromethyl-N,N-dimethylamine, 1,1-dichloromethyl-N,N-diethylamine, 1,1-dichloromethyl-N,N-diisopropylamine, 1,1-dichloro-N,N-2-trimethyl-1-propanamine, 1,1-dichloro-N,N-2,2-tetramethyl-1-propanamine (VIa), N,N-diethyl-alpha,alpha-dichloro-2,2-dimethyl-1-propanamine, N-(1,1-dichloromethyl)-morpholine, 1,1-dichloro-N,N-dimethyl-phenylmethanamine, N,N-diethyl-alpha,alpha-dichloro-3-pyridyl-methanamine and 2,2-dichloro-1,3,3-trimethylpyrrolidine. R4 = H, 1-12C alkyl, ((2-12C) alkylene-O)n-(1-12C) alkyl, 3-14C aryl or NR7R8; n = 1-5; R7, R8 = 1-8C alkyl; or NR7R8 = 4-7 membered cyclic residue with a total of 3-12C; R5, R6 = 1-12C alkyl; or R5 + R6 or R4 + R5 and/or R6 = group completing a 4-12C cyclic group.

Stereoelectronic effects on collagen stability: The dichotomy of 4-fluoroproline diastereomers

Collagen is the most abundant protein in animals. Natural collagen consists of a triple helix of (Xaa-Yaa-Gly)n chains, in which the Xaa and Yaa residues are often l-proline. Here, a (2S,4S)-4-fluoroproline (flp) residue is shown to be greatly stabilizing in the Xaa position (but destabilizing in the Yaa position). In contrast, a (2S,4R)-4-fluoroproline (Flp) residue is shown to be greatly destabilizing in the Xaa position (but stabilizing in the Yaa position). The dichotomous effect of the diastereomers appears to arise from a gauche effect, which alters pyrrolidine ring pucker and hence properly (or improperly) preorganizes main-chain dihedral angles. Thus, the rational use of stereoelectronic effects can enhance the conformational stability of a protein. Copyright