73283-54-2

Upstream product

• 67-56-1 methanol 
• 51-65-0 4-Fluorophenylalanine 
• 1612831-63-6 (E)-methyl 3-(4-fluorophenyl)-2-(hydroxyimino)propanoate 
• 176896-72-3 (S)-methyl 2-amino-3-(4-fluorophenyl)propanoate hydrochloride 
• 1323412-90-3 (S)-2-chloro-3-(4-fluorophenyl)propanoic acid 
• 1323413-01-9 (S)-methyl 2-chloro-3-(4-fluorophenyl)propanoate 
• 1323413-11-1 (R)-methyl 2-azido-3-(4-fluorophenyl)propanoate 
• 18125-46-7 (R)-4-fluorophenylalanine 
• 352-34-1 4-fluoro-1-iodobenzene 
• 1132-68-9 L-4-fluorophenylalanine 
• 460-00-4 1-Bromo-4-fluorobenzene 
• 1433460-20-8 methyl 2-(dibenzylamino)-3-(4-fluorophenyl)propanoate 

Downstream Products

• 169243-86-1 (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(4-fluorophenyl)propanoic acid 

Relevant academic research and scientific papers

Elucidating the Reaction Pathway of Decarboxylation-Assisted Olefination Catalyzed by a Mononuclear Non-Heme Iron Enzyme

Installation of olefins into molecules is a key transformation in organic synthesis. The recently discovered decarboxylation-assisted olefination in the biosynthesis of rhabduscin by a mononuclear non-heme iron enzyme (P.IsnB) represents a novel approach in olefin construction. This method is commonly employed in natural product biosynthesis. Herein, we demonstrate that a ferryl intermediate is used for C-H activation at the benzylic position of the substrate. We further establish that P.IsnB reactivity can be switched from olefination to hydroxylation using electron-withdrawing groups appended on the phenyl moiety of the analogues. These experimental observations imply that a pathway involving an initial C-H activation followed by a benzylic carbocation species or by electron transfer coupled β-scission is likely utilized to complete C=C bond formation.

NOVEL AMINOPEPTIDASE INHIBITORS AND METHODS OF USE

An aminopeptidase inhibitor compound comprising a biaryl, hydroxamic acid based core of formula: wherein X is a 5 or 6-membered ring, and including pharmaceutically acceptable salts and solvates thereof.

Potent dual inhibitors of Plasmodium falciparum M1 and M17 aminopeptidases through optimization of S1 pocket interactions

Malaria remains a global health problem, and though international efforts for treatment and eradication have made some headway, the emergence of drug-resistant parasites threatens this progress. Antimalarial therapeutics acting via novel mechanisms are urgently required. Plasmodium falciparum M1 and M17 are neutral aminopeptidases which are essential for parasite growth and development. Previous work in our group has identified inhibitors capable of dual inhibition of PfA-M1 and PfA-M17, and revealed further regions within the protease S1 pockets that could be exploited in the development of ligands with improved inhibitory activity. Herein, we report the structure-based design and synthesis of novel hydroxamic acid analogues that are capable of potent inhibition of both PfA-M1 and PfA-M17. Furthermore, the developed compounds potently inhibit Pf growth in culture, including the multi-drug resistant strain Dd2. The ongoing development of dual PfA-M1/PfA-M17 inhibitors continues to be an attractive strategy for the design of novel antimalarial therapeutics.

Ligand-enabled β-C-H arylation of α-amino acids using a simple and practical auxiliary

Pd-catalyzed β-C-H functionalizations of carboxylic acid derivatives using an auxiliary as a directing group have been extensively explored in the past decade. In comparison to the most widely used auxiliaries in asymmetric synthesis, the simplicity and practicality of the auxiliaries developed for C-H activation remains to be improved. We previously developed a simple N-methoxyamide auxiliary to direct β-C-H activation, albeit this system was not compatible with carboxylic acids containing α-hydrogen atoms. Herein we report the development of a pyridine-type ligand that overcomes this limitation of the N-methoxyamide auxiliary, leading to a significant improvement of β-arylation of carboxylic acid derivatives, especially α-amino acids. The arylation using this practical auxiliary is applied to the gram-scale syntheses of unnatural amino acids, bioactive molecules, and chiral bis(oxazoline) ligands.

LIGAND-CONTROLLED C(SP3)-H ARYLATION AND OLEFINATION IN SYNTHESIS OF UNNATURAL CHIRAL ALPHA AMINO ACIDS

The use of ligands to tune the reactivity and selectivity of transition metal-catalysts for C(-sp3)-H bond functionalization is a central challenge in synthetic organic chemistry. Herein, we report a rare example of catalyst-controlled C(sp3)-H arylation using pyridine and quinoline derivatives: the former promotes exclusive monoarylation, whereas the latter activates the catalyst further to achieve diarylation. Successive application of these ligands enables the sequential diarylation of a methyl group in an alanine derivative with two different aryl iodides, affording a wide range of β-Ar-p-Ar ' -cc-amino acids with excellent levels of diastereoselectivity (d.r. > 20:1). Both configurations of the β-chiral center can be accessed by choosing the order in which the aryl groups are installed. The use of a quinoline derivative as a ligand also enables C(sp3)-H olefination of a protected alanine.

FPR1 ANTAGONIST DERIVATIVES AND USE THEREOF

A dipeptide derivative as formyl peptide receptor 1 (FPR1) antagonist is provided. The dipeptide derivative is represented by formula (I), wherein: the chiral centers in formula (I) are S and R configurations respectively; each of RK and RT is selected from a group consisting of a hydrogen, a hydroxyl group, a C1-C4 alkyl-substituted hydroxyl group, a C1-C4 alkoxyl group, a carboxylic acid group, a C1-C4 alkyl nitrile-substituted, C1-C4 alkyl-substituted or C1-C4 alkoxyl-substituted amido group, a C1-C4 alkyl-substituted ester group and a benzoyl group having a C1-C4 alkyl-substituted benzene ring; and each of RM and RS is selected from a group consisting of a hydrogen, a hydroxyl group, a phenyl group, a pyridinyl group, a carboxylic acid group, a C1-C4 alkoxyl substituted ester group, and a benzoyl group having a hydroxyl-substituted, a halogen-substituted, a C1-C4 alkoxyl-substituted or a C1-C4 alkyl-substituted benzene ring.

MODULATORS OF REV-ERB

The subject matter herein concerns the identification and development of potent synthetic REV-ERB ligands, such as in vivo agonists and antagonists. These compounds allow for characterization of the effects of modulation of this receptor in vivo specifically on circadian behavior and metabolism, and have suitable characteristics for development of medicinal compounds useful for treatment of malconditions such as diabetes, obesity, atherosclerosis, dyslipidemia, a circadian rhythm disorder, coronary artery disease, bipolar disorder, depression, cancer, a sleep disorder, an anxiety disorder, an addiction disorder, a bone-related disorder such osteoporosis, a skeletal muscle disease, e.g., with compromised exercise capacity, or an autoimmune disorder such as psoriasis, multiple sclerosis, inflammatory bowel disease, and others.

Self-assembly of a tripeptide into a functional coating that resists fouling

This communication describes the self-assembly of a tripeptide into a functional coating that resists biofouling. Using this peptide-based coating we were able to prevent protein adsorption and interrupt biofilm formation. This coating can be applied on numerous substrates and therefore can serve in applications related to health care, marine and water treatment.

Fixation and recycling of nitrogen monoxide through carbonitrosation reactions

The removal of nitrogen monoxide from gas streams through complexation to iron(ii) ions in aqueous dimethylsulfoxide can be combined with a new variant of the Meerwein arylation, which incorporates the previously complexed NO into organic compounds to give oximes as final products. The first step of this two-step process has been evaluated regarding the effectiveness of the NO absorption and the sensitivity of the aqueous iron(ii)-DMSO solution towards oxygen from air, in both cases in comparison with the known BioDeNOx process. The subsequent Meerwein arylation, which was designed with the intention to make use of nitrogen monoxide as the simplest nitrogen-centered radical scavenger, is shown to tolerate an exceptionally broad spectrum of substituents on the aromatic core of the diazonium salts including electron-donating as well as electron-withdrawing substituents. Under simple conditions the resulting oximes can be converted to racemic amino acid esters. This journal is the Partner Organisations 2014.

Effect of the 4′-substituted phenylalanine moiety of sansalvamide A peptide on antitumor activity

Eight sansalvamide A peptide analogues with 4′-fluoride, 4′-chloride, 4′-bromide, 4′-iodide, and 4′- methoxyphenylalanine moieties were synthesized. The effect of these para-substitutions of sansalvamide A peptide on their cytotoxicity was evaluated using HCT-116, MDA-MB-231, HT-29, HCT-15, K562, HeLa, and A549 cell lines. The 4′-methoxyphenylalanine analog of sansalvamide A peptide was found to be a promising antitumor agent.