67729-36-6

Upstream product

• 18942-49-9 Boc-D-Phe-OH 
• 543-27-1 isobutyl chloroformate 
• 24424-99-5 di-tert-butyl dicarbonate 
• 63-91-2 L-phenylalanine 
• 13734-34-4 N-tert-butoxycarbonyl-L-phenylalanine 

Downstream Products

• 60398-41-6 (3S)-tert-butyl 1-benzyl-3-diazo-2-oxopropylcarbamate 
• 123068-64-4 Boc-L-Phe-BPP 
• 7625-57-2 methyl 2-((2S)-2-((tert-butoxycarbonyl)amino)-3-phenylpropanamido)acetate 
• 13122-89-9 (S)-methyl 2-((S)-2-(tert-butoxycarbonylamino)-3-phenylpropanamido)-3-phenylpropanoate 
• 77076-37-0 {(S)-1-[(S)-1-(2-Chloro-acetyl)-3-methyl-butylcarbamoyl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester 
• 87694-53-9 Boc-Phe-OH N,O-dimethyl hydroxamate 
• 122663-41-6 ((S)-1-{(S)-1-[(1S,2S)-1-Cyclohexylmethyl-2-((S)-1-cyclohexyl-2-oxo-pyrrolidin-3-yl)-2-hydroxy-ethylcarbamoyl]-2-[1-(2,4-dinitro-phenyl)-1H-imidazol-4-yl]-ethylcarbamoyl}-2-phenyl-ethyl)-carbamic acid tert-butyl ester 
• 122682-25-1 ((S)-1-{(S)-1-[(1S,2R)-1-Cyclohexylmethyl-2-hydroxy-2-(1-methyl-2-oxo-pyrrolidin-3-yl)-ethylcarbamoyl]-2-[1-(2,4-dinitro-phenyl)-1H-imidazol-4-yl]-ethylcarbamoyl}-2-phenyl-ethyl)-carbamic acid tert-butyl ester 
• 122682-25-1 ((S)-1-{(S)-1-[(1S,2S)-1-Cyclohexylmethyl-2-hydroxy-2-((S)-1-methyl-2-oxo-pyrrolidin-3-yl)-ethylcarbamoyl]-2-[1-(2,4-dinitro-phenyl)-1H-imidazol-4-yl]-ethylcarbamoyl}-2-phenyl-ethyl)-carbamic acid tert-butyl ester 
• 122682-25-1 ((S)-1-{(S)-1-[(1S,2S)-1-Cyclohexylmethyl-2-hydroxy-2-((R)-1-methyl-2-oxo-pyrrolidin-3-yl)-ethylcarbamoyl]-2-[1-(2,4-dinitro-phenyl)-1H-imidazol-4-yl]-ethylcarbamoyl}-2-phenyl-ethyl)-carbamic acid tert-butyl ester 
• 76948-01-1 Boc-Phe-Lys(N^e-Cbz)-Leu-Gly-OEt 
• 86029-07-4 Boc-Phe-N-Me-Ala-Tyr-OMe 

Relevant academic research and scientific papers

C12 helices in long hybrid (αγ)n peptides composed entirely of unconstrained residues with proteinogenic side chains

Unconstrained γ4 amino acid residues derived by homologation of proteinogenic amino acids facilitate helical folding in hybrid (αγ)n sequences. The C12 helical conformation for the decapeptide, Boc-[Leu-γ4(R)Val

A multifaceted secondary structure mimic based on piperidine-piperidinones

Minimalist secondary structure mimics are typically made to resemble one interface in a protein-protein interaction (PPI), and thus perturb it. We recently proposed suitable chemotypes can be matched with interface regions directly, without regard for secondary structures. Here we describe a modular synthesis of a new chemotype 1, simulation of its solution-state conformational ensemble, and correlation of that with ideal secondary structures and real interface regions in PPIs. Scaffold 1 presents amino acid side-chains that are quite separated from each other, in orientations that closely resemble ideal sheet or helical structures, similar non-ideal structures at PPI interfaces, and regions of other PPI interfaces where the mimic conformation does not resemble any secondary structure. 68 different PPIs where conformations of 1 matched well were identified. A new method is also presented to determine the relevance of a minimalist mimic crystal structure to its solution conformations. Thus dld-1-faf crystallized in a conformation that is estimated to be 0.91 kcal-mol-1 above the minimum energy solution state. Do we know, when designing a new peptidomimetic scaffold like the one shown, how it can resemble secondary structures? Design and modular synthesis of this elongated mimic is reported, and the structure is related to ideal and real structures at PPI interfaces.

Process for the preparation of ibodutant (MEN15596) and related intermediates

This invention relates to a novel process for synthesizing the product ibodutant shown in the figure below, consisting of a small number of high-yield steps involving reagents and solvents with low environmental impact, characterized by the coupling of two portions, compounds (3) and (4), one of which (3) is synthesized by coupling of 6-methyl-2-benzo[b]thiophenecarboxylic acid (1) with 1-amino-alpha-alpha-cyclopentan carboxylic acid and subsequent cyclization with oxazolone, while the other, compound (4), is obtained from suitable highly selective functionalizations of 4-aminomethylpiperidine (2).

α-N-Protected dipeptide acids: A simple and efficient synthesis via the easily accessible mixed anhydride method using free amino acids in DMSO and tetrabutylammonium hydroxide

The importance of dipeptides both in medicinal and pharmacological fields is well documented and many efforts have been made to find simple and efficient methods for their synthesis. For this reason, we have investigated the synthesis of α-N-protected dipeptide acids by reacting the easily accessible mixed anhydride of α-N-protected amino acids with free amino acids under different reaction conditions. The combination of TBA-OH and DMSO has been found to be the best to overcome the low solubility of amino acids in organic solvents. Under these experimental conditions, the homogeneous phase condensation reaction occurs rapidly and without detectable epimerization. The present method is also applicable to side-chain unprotected Tyr, Trp, Glu, and Asp but not Lys. This latter residue is able to engage two molecules of mixed anhydride giving the corresponding isotripeptide. Moreover, the applicability of this protocol for the synthesis of tri- and tetrapeptides has been tested. This approach reduces the need for protecting groups, is cost effective, scalable, and yields dipeptide acids that can be used as building blocks in the synthesis of larger peptides.

Sodium borohydride reduction of carbamoyl azide function: A synthesis of N-protected N'-formyl-gem-diaminoalkyl derivatives

A simple, efficient two-step synthesis of N-protected N′-formyl-gem- diaminoalkyl derivatives is reported. The procedure involves the unprecedented reduction of the carbamoyl azide of α-N-Boc/Fmoc/Z-protected amino acids and dipeptides (Boc = tert-butoxycarbonyl, Fmoc = 9-fluorenylmethoxycarbonyl, Z = benzyloxycarbonyl) by treatment with NaBH4 at room temperature. The reaction proceeds rapidly (45 min) without detectable epimerization (by HPLC-ESI-MS analysis) and is not influenced by the nature of the starting carbamoyl azide. The 1H and 13C NMR analyses of the synthesized N-protected N′-formamides were carried out in [D 6]DMSO. The spectra exhibited the presence of two rotameric forms in solution as a result of the restricted rotation around the N-CO formyl bond. The integration of the N-CH-N protons of the two isomers showed that the cis isomer (rotamer B) was the more abundant conformer by 60 to 78 %. The reported synthesis represents the potential value of carbamoyl azides as versatile chiral starting materials for many synthetic purposes. A simple two-step synthesis of N-protected N′-formyl-gem-diaminoalkyl derivatives is reported that employs the reduction of the carbamoyl azide of N-protected amino acids and N-protected dipeptide acids with NaBH4. This racemization-free protocol is compatible with the most commonly used N-protecting groups. Copyright

Active site mapping of trypsin, thrombin and matriptase-2 by sulfamoyl benzamidines

The benzamidine moiety, a well-known arginine mimetic, has been introduced in a variety of ligands, including peptidomimetic inhibitors of trypsin-like serine proteases. According to their primary substrate specificity, the benzamidine residue interacts with the negatively charged aspartate at the bottom of the S1 pocket of such enzymes. Six series of benzamidine derivatives (1-73) were synthesized and evaluated as inhibitors of two prototype serine proteases, that is, bovine trypsin and human thrombin. As a further target, human matriptase-2, a recently discovered type II transmembrane serine protease, was investigated. Matriptase-2 represents an important regulatory protease in iron homeostasis by down-regulation of the hepcidin expression. Compounds 1-73 were designed to contain a fixed sulfamoyl benzamidine moiety as arginine mimetic and a linker-connected additional substructure, such as a tert-butyl ester, carboxylate or second benzamidine functionality. A systematic mapping approach was performed with these inhibitors to scan the active site of the three target proteases. In particular, bisbenzamidines, able to interact with both the S1 and S3/S4 binding sites, showed notable affinity. In branched bisbenzamidines 66-73 containing a third hydrophobic residue, opposite effects of the stereochemistry on trypsin and thrombin inhibition were observed.

Solution-phase synthesis of novel seven-membered cyclic dipeptides containing α- And β-amino acids

A convenient synthetic procedure for the preparation of seven-membered cyclic α,β-dipeptides is described. Following coupling of N-protected α-amino acids with N-substituted β-amino acid tert-butyl esters, that affords linear α,β-dipeptides, the protecting groups at the terminal functionalities were removed and the open-chain dipeptides were cyclized with phenylphosphonic dichloride, PhP(O)Cl2, to give the desired cyclic α,β-dipeptides in good yields. NMR studies, X-ray diffraction analysis, and DFT calculations provided evidence for the conformation adopted by these cyclic dipeptides in solution, in the solid-state, and in the gas phase.

RTD-1 mimic containing γPNA scaffold exhibits broad-spectrum antibacterial activities

Macrocyclic peptides with multiple disulfide cross-linkages, such as those produced by plants and those found in nonhuman primates, as components of the innate immunity, hold great promise for molecular therapy because of their broad biological activities

Fabrication of nanostructures through molecular self-assembly of small amphiphilic glyco-dehydropeptides

Self-assembled peptide-based nanostructures have been the focus of research in the past decade because of their potential applications in various biological systems. Normally, small self-assembled peptide nanostructures contain hydrophobic moieties, there

Discovery, synthesis, and biological evaluation of a novel group of selective inhibitors of filoviral entry

Herein, we report the development of an antifiloviral screening system, based on a pseudotyping strategy, and its application in the discovery of a novel group of small molecules that selectively inhibit the Ebola and Marburg glycoprotein (GP)-mediated infection of human cells. Using Ebola Zaire GP-pseudotyped HIV particles bearing a luciferase reporter gene and 293T cells, a library of 237 small molecules was screened for inhibition of GP-mediated viral entry. From this assay, lead compound 8a was identified as a selective inhibitor of filoviral entry with an IC50 of 30 μM. To analyze functional group requirements for efficacy, a structure-activity relationship analysis of this 3,5-disubstituted isoxazole was then conducted with 56 isoxazole and triazole derivatives prepared using "click" chemistry. This study revealed that while the isoxazole ring can be replaced by a triazole system, the 5-(diethylamino)acetamido substituent found in 8a is required for inhibition of viral-cell entry. Variation of the 3-aryl substituent provided a number of more potent antiviral agents with IC50 values ranging to 2.5 μM. Lead compound 8a and three of its derivatives were also found to block the Marburg glycoprotein (GP)-mediated infection of human cells.