84028-86-4

Upstream product

• 358-23-6 trifluoromethylsulfonic anhydride 
• 13673-95-5 (S)-methyl 2-hydroxy-3-phenylpropanoate 
• 27000-00-6 methyl 2-hydroxy-3-phenylpropionate 
• 828-01-3 D-phenyllactic acid 
• 673-06-3 D-(R)-phenylalanine 
• 182937-63-9 (R)-2-(benzyloxy)-3-phenylpropanoic acid 

Downstream Products

• 170211-71-9 (S)-Methyl 2-benzyl-4-oxopentanoate 
• 99209-17-3 (2R,1'S)-N-<1-(Ethoxycarbonyl)ethyl>phenylalanin-methylester 
• 99209-17-3 (2R,1'R)-N-<1-(Ethoxycarbonyl)ethyl>phenylalanin-methylester 
• 55322-26-4 N-Benzyloxy-D-phenylalanin-methylester 
• 99209-20-8 (2R,1'S)-N-(1-Phenylethyl)-phenylalanin-methylester 
• 103954-26-3 (S)-2-((R)-1-Methoxycarbonyl-2-phenyl-ethylamino)-3-phenyl-propionic acid methyl ester 
• 84028-92-2 (2R,2'R)-2-(2-Ethylpiperidino)-3-phenyl-propionsaeure-methylester 
• 174799-58-7 (R)-2-[Benzyl-(3-tert-butoxycarbonylamino-propyl)-amino]-3-phenyl-propionic acid methyl ester 
• 1379682-38-8 (R)-(-)-Nα-iso-propyl-Nβ-Boc-(D)-hydrazinophenylalanine methyl ester 
• 1197031-90-5 (R)-(-)-Nα-methyl-Nβ-Boc-(D)-hydrazinophenylalanine methyl ester 
• 1379682-37-7 (R)-(-)-Nα-iso-butyl-Nβ-Boc-(D)-hydrazinophenylalanine methyl ester 
• 1379682-36-6 (R)-(-)-Nα-benzyl-Nβ-Boc-(D)-hydrazinophenylalanine methyl ester 
• 171818-47-6 (S)-2-(3-Benzylsulfanyl-propylamino)-3-phenyl-propionic acid methyl ester 
• 174799-55-4 (S)-2-[Benzyl-(3-tert-butoxycarbonylamino-propyl)-amino]-3-phenyl-propionic acid methyl ester 

Relevant academic research and scientific papers

The discovery of a potent series of carboxamide TRPA1 antagonists

A series of potent and selective carboxamide TRPA1 antagonists were identified by a high throughput screen. Structure-activity relationship studies around this series are described, resulting in a highly potent example of the series. Pharmacokinetic and skin flux data are presented for this compound. Efficacy was observed in a topical cinnamaldehyde flare study, providing a topical proof of pharmacology for this mechanism. These data suggest TRPA1 antagonism could be a viable mechanism to treat topical conditions such as atopic dermatitis.

Glycerol conversion to high-value chemicals: The implication of unnatural α-amino acid syntheses using natural resources

Glycerol derivatives are an important class of compounds, which have great applications as basic structural building blocks in organic synthesis. O-Benzylglycerol was oxidised to produce a high-value compound in high yield using a NaOtBu-O2 system. Furthermore, the synthetic utility of the resulting product was demonstrated by its transformation into unnatural α-amino acids, thus showing the valorisation of glycerol biomass.

Solid-phase synthesis of tetrahydropyridazinedione-constrained peptides

The design and solid-phase synthesis of tetrahydropyridazine-3,6-dione (Tpd) peptidomimetics derived from backbone-aminated peptides is reported. The described protocol features the synthesis of chiral α-hydrazino acids suitable for chemoselective incorporation into growing peptide chains. Acid-catalyzed cyclization to form the Tpd ring during cleavage affords the target peptidomimetics in good yield and purity. The scope of Tpd incorporation is demonstrated through the synthesis of constrained peptides featuring nucleophilic/electrophilic side chains and sterically encumbered α-substituted hydrazino acid residues. (Chemical Equation Presented).

An expedient and short synthesis of chiral α-hydrazinoesters: Synthesis and conformational analysis of 1:1 [α/α-N α-hydrazino]mers

Different α-hydrazinoesters with high optical purity have been obtained in large scale via an SN2 protocol. A coupling reaction with a natural amino acid leads to the corresponding dimers, which have been oligomerized in order to obtain the 1:1 [α/α-Nα- hydrazino]mer series. Conformational studies show that these mixed oligomers are self-organized in solution via a succession of γ-turn and hydrazinoturn whatever the absolute configuration of the chiral carbons.

Peptide ligation assisted by an auxiliary attached to amidyl nitrogen

New thiol-containing auxiliaries were developed for peptide ligation. They were placed at the amidyl N-atom in the second amino acid residue of a peptide fragment. With the new auxiliaries, peptide ligation could be conducted at non-Cys and non-Gly sites. Compared to other recently developed auxiliaries, an important feature of the present design was that the new auxiliaries were generally applicable and readily removable.

Design and synthesis of novel 2-pyridone peptidomimetic falcipain 2/3 inhibitors

The structure-based design, chemical synthesis and in vitro activity evaluation of various falcipain inhibitors derived from 2-pyridone are reported. These compounds contain a peptidomimetic binding determinant and a Michael acceptor terminal moiety capable of deactivating the cysteine protease active site.

Synthesis of isotopically labeled puromycin derivatives for kinetic isotope effect analysis of ribosome catalyzed peptide bond formation

The mechanism by which the ribosome catalyze peptide bond formation remains controversial. Here we describe the synthesis of dinucleotides that can be used in kinetic isotope effect experiments to assess the transition state of ribosome catalyzed peptide

Design, synthesis, and evaluation of matrix metalloprotease inhibitors bearing cyclopropane-derived peptidomimetics as P1′ and P2′ replacements

We have previously used trisubstituted cyclopropanes as peptide replacements to induce conformational constraints in known pseudopeptide inhibitors of a number of important enzymes. Cyclopropane-derived peptide mimics are novel in that they are among the few replacements that locally orient the peptide backbone and the amino acid side chain in a predefined manner. Although these dipeptide isosteres have been employed to orient amino acid side chains mimicking the gauche(-) conformation of χ1-space, their ability to project the side chains into an anti orientation has not been evaluated. As a first step toward this goal, the conformationally constrained pseudopeptides 8 and 10 and their corresponding flexible analogues 9 and 11 were prepared and tested as inhibitors of matrix metalloproteinases (MMPs). These compounds are analogues of 4 and 5, which were known to be potent MMP inhibitors. The anti orientations of the isopropyl side chain in 8 and the aromatic ring in 10 relative to the peptide backbone substituents on the cyclopropane were predicted to correspond to the known orientations of the P1′ and P2′ side chains of 5 when bound to MMPs. Hence, 8 and 10 were designed explicitly to probe topological features of the S1′ or the S2′ binding pockets of the MMPs. They were also designed to explore the importance of the P1′-P2′ amide group, which is known to form highly conserved hydrogen bonds in several MMP-inhibitor complexes, and the viability of introducing a retro amide linkage between P2′ and P3′. Pseudopeptides 8 and 9 were found to be weak competitive inhibitors of a series of MMPs. Any entropically favorable conformational constraints that were induced by the cyclopropane in 8 were thus overwhelmed by the loss of the hydrogen bonding capability associated with the P1′-P2′ amide group. On the other hand, compounds 10 and 11, which contain a P2′-P3′ retro amide group, were modest competitive inhibitors of a series of MMPs. The results obtained for 10 and 11 suggest that there may be a loss of hydrogen bonding capability associated with introducing the P2′-P3′ retro amide group. However, because the conformationally constrained pseudopeptide 10 was significantly more potent than its flexible analogue 11, trisubstituted cyclopropanes related to 3 may serve as useful rigid dipeptide replacements in some biologically active pseudopeptides.

Structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3C protease inhibitors. 3. Structure-activity studies of ketomethylene-containing peptidomimetics

The structure-based design, chemical synthesis, and biological evaluation of various ketomethylene-containing human rhinovirus (HRV) 3C protease (3CP) inhibitors are described. These compounds are comprised of a peptidomimetic binding determinant and an e

Ribosome-mediated incorporation of hydrazinophenylalanine into modified peptide and protein analogues

(S)-α-Hydrazinophenylalanyl-tRNA(Phe), an aminoacyl-tRNA derivative containing the unnatural amino acid (S)-α-hydrazinophenylalanine, was prepared in an effort to examine the stereochemical requirements of the A- site of the ribosome during in vitro protein synthesis. The (S)-α- hydrazinophenylalanine moiety was of interest because it contains two nucleophilic centers, the secondary nitrogen attached to C(α), which is normally acylated during the course of peptide bond formation, and the sterically less hindered primary nitrogen. To determine the position of acylation, (S)-α-hydrazinophenylalanyl-tRNA(Phe) was tested in an Escherichia cull in vitro protein biosynthesizing system lacking elongation factor G, such that only dipeptide products were formed. The dipeptide product mixture was analyzed by HPLC in direct comparison with authentic synthetic standards. The dipeptide assay utilizing (S)-α- hydrazinophenylalanyl-tRNA(Phe) as the A-site tRNA established that the analogue functioned well as an acceptor tRNA; HPLC analysis of the products showed that both dipeptides were formed in approximately equal amounts. When attached to a suppressor tRNA transcript, (S)-α-hydrazinophenylalanine was also incorporated into position 27 of dihydrofolate reductase in an E. coli protein synthesizing system by readthrough of a nonsense codon. This finding expands the currently accepted model of peptide bond formation at the ribosome and adds to the repertoire of peptide-like products shown to form at the peptidyltransferase center of the ribosome.