35373-92-3

Upstream product

• 15368-72-6 (S)-N-Benzyloxycarbonyl-phenylalanine-N'-methylamide 
• 63-91-2 L-phenylalanine 
• 74-89-5 methylamine 
• 1161-13-3 N-Cbz-L-Phe 
• 13734-34-4 N-tert-butoxycarbonyl-L-phenylalanine 
• 3182-93-2 (L)-phenylalanine ethyl ester hydrochloride 
• 2577-90-4 methyl (2S)-2-amino-3-phenylpropanoate 
• 87877-11-0 Phe-Chlor 
• 203446-11-1 Trt-(L)-Phe-NHMe 
• 7524-50-7 methyl (2S)-2-amino-3-phenylpropanoate hydrochloride 
• 3081-24-1 H-Phe-OEt 
• 124-40-3 dimethyl amine 
• 120346-32-9 (3S,4R)-1-methyl-4-phenyl-3-[(4S)-4-phenyl-2-oxo-1,3-oxazolidin-3-yl]-azetidin-2-one 
• 109522-21-6 N-(t-butoxycarbonyl)-L-phenylalanine methylamide 

Downstream Products

• 129155-77-7 (S)-5-Benzyl-2-(4-methoxy-phenyl)-3-methyl-imidazolidin-4-one 
• 415678-40-9 (2R,5S)-5-benzyl-3-methyl-2-(5-methyl-furan-2-yl)-imidazolidin-4-one 
• 415678-40-9 (2S,5S)-5-benzyl-3-methyl-2-(5-methyl-furan-2-yl)-imidazolidin-4-one 
• 415678-38-5 (2S,5S)-5-benzyl-3-methyl-2-phenylimidazolidin-4-one 
• 415678-38-5 (2R,5S)-5-benzyl-3-methyl-2-phenylimidazolidin-4-one 
• 908350-12-9 (2R)-N¹-[(1S)-1-(methylcarbamoyl)-2-phenylethyl]-N⁴-hydroxy-2-isobutyl-3-methylenesuccinamide 
• 130370-62-6 S-(2S,3R)-3-[(1S)-1-(methylcarbamoyl)-2-phenylethylcarbamoyl]-2-(hydroxycarbamoyl)-5-methylhexyl ethanethioate 
• 198409-67-5 (3R)-3-[(1S)-1-(methylcarbamoyl)-2-phenylethylcarbamoyl]-5-methyl-2-methylenehexanoic acid 
• 198409-70-0 (2S,3R)-2-Mercaptomethyl-5-methyl-3-((S)-1-methylcarbamoyl-2-phenyl-ethylcarbamoyl)-hexanoic acid 
• 198409-69-7 (2S,3R)-2-Acetylsulfanylmethyl-5-methyl-3-((S)-1-methylcarbamoyl-2-phenyl-ethylcarbamoyl)-hexanoic acid 

Relevant academic research and scientific papers

Pd-Catalysed oxidative carbonylation of α-amino amides to hydantoins under mild conditions

The first example of palladium-catalysed oxidative carbonylation of unprotected α-amino amides to hydantoins is described here. The selective synthesis of the target compounds was achieved under mild conditions (1 atm of CO), without ligands and bases. The catalytic system overrode the common reaction pathway that usually leads instead to the formation of symmetrical ureas.

Asymmetric hydroalkylation of alkynes and allenes with imidazolidinone derivatives: α-alkenylation of α-amino acids

This work reports a new method for the synthesis of quaternary α-alkenyl substituted amino acids by the enantio- and diastereoselective addition of imidazolidinone derivatives to alkynes and allenes. Further hydrolysis of the imidazolidinone products under acidic conditions afforded biologically relevant amino acid derivatives. This method is geometry-selective (E-isomer), enantio- and diastereoselective, and products were obtained in good to excellent yields. The utility of this new methodology is proved by its operational simplicity and the successful accomplishment of gram-scale reactions. Experimental and computational studies suggest the key role of Li in terms of selectivity and support the proposed reaction mechanism.

Asymmetric and Geometry-Selective α-Alkenylation of α-Amino Acids

Both E- and Z-N′-alkenyl urea derivatives of imidazolidinones may be formed selectively from enantiopure α-amino acids. Generation of their enolate derivatives in the presence of K+ and [18]crown-6 induces intramolecular migration of the alkeny

Design, synthesis, and functional assessment of Cmpd-15 derivatives as negative allosteric modulators for the β2-adrenergic receptor

The β2-adrenergic receptor (β2AR), a G protein-coupled receptor, is an important therapeutic target. We recently described Cmpd-15, the first small molecule negative allosteric modulator (NAM) for the β2AR. Herein we report in details the design, synthesis and structure-activity relationships (SAR) of seven Cmpd-15 derivatives. Furthermore, we provide in a dose-response paradigm, the details of the effects of these derivatives in modulating agonist-induced β2AR activities (G-protein-mediated cAMP production and β-arrestin recruitment to the receptor) as well as the binding affinity of an orthosteric agonist in radio-ligand competition binding assay. Our results show that some modifications, including removal of the formamide group in the para-formamido phenylalanine region and bromine in the meta-bromobenzyl methylbenzamide region caused dramatic reduction in the functional activity of Cmpd-15. These SAR results provide valuable insights into the mechanism of action of the NAM Cmpd-15 as well as the basis for future development of more potent and selective modulators for the β2AR based on the chemical scaffold of Cmpd-15.

UNNATURAL AMINO ACIDS

The present invention relates to a process for the preparation compounds of Formula (I): Formula (I) wherein X, Z, Q, Ar, R1, R2, R3 and R4 are each as defined herein. The present invention also relates to processes for the preparation of the compounds of quaternary amino acids and hydantions, to compound of Formula(I), to intermediate compounds of Formula (II), to quaternary amino acid compounds of Formula (III) and to hydantoin compounds of Formula (IV).

Substituted Dihydroisoquinolinones by Iodide-Promoted Cyclocarbonylation of Aromatic α-Amino Acids

Imidazolidinone derivatives of a range of aromatic α-amino acids, on treatment with phosgene and potassium iodide, undergo a mild Bischler-Napieralski-style cyclocarbonylation reaction that generates a tricyclic lactam by insertion of a C=O group between amino acid nitrogen and the ortho position of the aryl substituent. Regio- and diastereoselective functionalization of the lactam generates a library of substituted dihydroisoquinolinones and their congeners in enantioenriched form.

Spin-Center Shift-Enabled Direct Enantioselective α-Benzylation of Aldehydes with Alcohols

Nature routinely engages alcohols as leaving groups, as DNA biosynthesis relies on the removal of water from ribonucleoside diphosphates by a radical-mediated "spin-center shift" (SCS) mechanism. Alcohols, however, remain underused as alkylating agents in synthetic chemistry due to their low reactivity in two-electron pathways. We report herein an enantioselective α-benzylation of aldehydes using alcohols as alkylating agents based on the mechanistic principle of spin-center shift. This strategy harnesses the dual activation modes of photoredox and organocatalysis, engaging the alcohol by SCS and capturing the resulting benzylic radical with a catalytically generated enamine. Mechanistic studies provide evidence for SCS as a key elementary step, identify the origins of competing reactions, and enable improvements in chemoselectivity by rational photocatalyst design.

A Bifunctional Photoaminocatalyst for the Alkylation of Aldehydes: Design, Analysis, and Mechanistic Studies

A bifunctional photoaminocatalyst based on imidazolidinone and thioxanthone is presented. The preparation of these catalysts proceeds in a two-step synthesis that allows an easy tuning of the steric properties. The photophysical and electrochemical data of the imidazolidinone photocatalysts have been determined, indicating that the catalysts can work under visible light conditions. To corroborate the experimental observations, ground state geometry optimization and energy transition studies of thioxanthone and bifunctional catalyst 4c were optimized by time-dependent density functional theory (TD DFT) calculations. The alkylation of aldehydes with this photoaminocatalyst works with high enantioselectivities and yields due to the stereoelectronic properties of the catalyst. A rational mechanistic cycle based on different mechanistic experiments, TD DFT calculations, and laser flash photolysis is presented.

Aromatic Interactions in Organocatalyst Design: Augmenting Selectivity Reversal in Iminium Ion Activation

Substituting N-methylpyrrole for N-methyindole in secondary-amine-catalysed Friedel-Crafts reactions leads to a curious erosion of enantioselectivity. In extreme cases, this substrate dependence can lead to an inversion in the sense of enantioinduction. Indeed, these closely similar transformations require two structurally distinct catalysts to obtain comparable selectivities. Herein a focussed molecular editing study is disclosed to illuminate the structural features responsible for this disparity, and thus identify lead catalyst structures to further exploit this selectivity reversal. Key to effective catalyst re-engineering was delineating the non-covalent interactions that manifest themselves in conformation. Herein we disclose preliminary validation that intermolecular aromatic (CH-π and cation-π) interactions between the incipient iminium cation and the indole ring system is key to rationalising selectivity reversal. This is absent in the N-methylpyrrole alkylation, thus forming the basis of two competing enantio-induction pathways. A simple L-valine catalyst has been developed that significantly augments this interaction.

Enantioselective oxidation of thioanisole to metyl phenyl sulfoxide by chiral compounds bearing N-Cl bond

Chiral sulfoxides are used in asymmetric synthesis and are present in various biologically active compounds. Asymmetric synthesis of the sulfoxides has been performed by chiral metal complexes and non-metals containing peroxide and oxide moieties. In this study, a new metal free method has been developed to oxidize thioanisole into methyl phenyl sulfoxide with easily accessible chiral compounds carrying N-Cl bond. For this purpose, chiral amine and amide bearing reagents were synthesized and chlorinated by using N-chlorosuccinimide. In oxidation reactions, chiral information has been transferred from N-chloramines to sulfides. With chlorinated chiral reagents, we observed enantioenriched sulfoxide formation. Although the observed results are promising, the best chiral amines are yet to be found. This is the first report on such a reaction, to the best of our knowledge.