68870-85-9

Upstream product

• 15028-44-1 DL-phenylalanine methyl ester 
• 100-52-7 benzaldehyde 
• 5619-07-8 methyl 2-amino-3-phenylpropanoate hydrochloride 
• 7524-50-7 methyl (2S)-2-amino-3-phenylpropanoate hydrochloride 
• 2577-90-4 methyl (2S)-2-amino-3-phenylpropanoate 
• 63-91-2 L-phenylalanine 
• 150-30-1 Phenylalanine 
• 40216-75-9 N-benzylidene-L-serine methyl ester 
• 23402-69-9 Li⁽¹⁺⁾*{Cu(C₆H₅)2}^(1-)*LiI=Li{Cu(C₆H₅)2}*LiI 
• 70361-62-5 2-(Benzylidenamino)propensaeure-methylester 
• 591-51-5 phenyllithium 
• 89891-09-8 Imidazole-1-carboxylic acid (S)-2-methoxycarbonyl-2-{[1-phenyl-meth-(E)-ylidene]-amino}-ethyl ester 

Downstream Products

• 70471-06-6 2-Chloromethyl-3-phenyl-2-{[1-phenyl-meth-(Z)-ylidene]-amino}-propionic acid methyl ester 
• 70471-12-4 2-Benzyl-3,3-difluoro-2-{[1-phenyl-meth-(Z)-ylidene]-amino}-propionic acid methyl ester 
• 64665-60-7 DL-α-methylphenylalanine methyl ester hydrochloride 
• 78031-66-0 Ac-DL-Phe-DL-Phe-OMe 
• 54551-10-9 2-(2-Hydroxy-3-phenyl-propionylamino)-3-phenyl-propionic acid methyl ester 
• 1374460-22-6 C₂₃H₂₃NO₅ 
• 1374460-28-2 C₂₃H₂₃NO₅ 
• 1443036-63-2 (2S,3R,4R,5S)-methyl 2-benzyl-4-nitro-3,5-diphenylpyrrolidine-2-carboxylate 
• 1310430-67-1 (2S,4S,5S)-dimethyl 2-benzyl-5-phenylpyrrolidine-2,4-dicarboxylate 

Relevant academic research and scientific papers

Nitroxyl Catalysts for Six-Membered Ring Bromolactonization and Intermolecular Bromoesterification of Alkenes with Carboxylic Acids

We developed a nitroxyl-catalyzed bromoesterification of alkenes with bromo reagents, which includes a six-membered ring bromolactonization of alkenyl carboxylic acids catalyzed by AZADO as the nitroxyl radical catalyst, and an intermolecular bromoesterification of alkenes with carboxylic acids using NMO as the N-oxide catalyst. We also accomplished a remote diastereoselective bromohydroxylation via an AZADO-catalyzed six-membered ring bromolactonization and a subsequent ring cleavage reaction with alkylamines to furnish ?-bromo-δ-hydroxy amides with high diastereoselectivity.

Synthesis and Penicillin-binding Protein Inhibitory Assessment of Dipeptidic 4-Phenyl-β-lactams from α-Amino Acid-derived Imines

Monocyclic β-lactams revive the research field on antibiotics, which are threatened by the emergence of resistant bacteria. A six-step synthetic route was developed, providing easy access to new 3-amino-1-carboxymethyl-4-phenyl-β-lactams, of which the penicillin-binding protein (PBP) inhibitory potency was demonstrated biochemically.

Re-Engineering Organocatalysts for Asymmetric Friedel-Crafts Alkylation of Indoles through Computational Studies

The discovery of efficient organocatalysts is generally carried out by thorough experimental screening of different candidates. We recently reported an efficient organocatalyst for iminium-ion-based asymmetric Diels-Alder reactions following a rational design approach. This result encouraged us to test this optimal catalyst in the mechanistically related Friedel-Crafts alkylation of indoles, but to our surprise, almost null enantioselectivity was observed. The results did not significantly improve with structurally related catalysts, and a totally unexpected facial selectivity inversion was also noticed. Using DFT calculations by modeling the competing transition structures with ONIOM, we could unravel the origins of those findings, further employed to predict the most efficient catalyst for this new transformation. The computational results were validated experimentally (up to 92:8 er), providing another successful example of a general strategy to accelerate catalyst development which still remains underexplored.

Utilization of fluoroform for difluoromethylation in continuous flow: A concise synthesis of α-difluoromethyl-amino acids

Fluoroform (CHF3) can be considered as an ideal reagent for difluoromethylation reactions. However, due to the low reactivity of fluoroform, only very few applications have been reported so far. Herein we report a continuous flow difluoromethyl

Synthesis and Deployment of an Elusive Fluorovinyl Cation Equivalent: Access to Quaternary α-(1′-Fluoro)vinyl Amino Acids as Potential PLP Enzyme Inactivators

Developing specific chemical functionalities to deploy in biological environments for targeted enzyme inactivation lies at the heart of mechanism-based inhibitor development but also is central to other protein-tagging methods in modern chemical biology including activity-based protein profiling and proteolysis-targeting chimeras. We describe here a previously unknown class of potential PLP enzyme inactivators; namely, a family of quaternary, α-(1′-fluoro)vinyl amino acids, bearing the side chains of the cognate amino acids. These are obtained by the capture of suitably protected amino acid enolates with β,β-difluorovinyl phenyl sulfone, a new (1′-fluoro)vinyl cation equivalent, and an electrophile that previously eluded synthesis, capture and characterization. A significant variety of biologically relevant AA side chains are tolerated including those for alanine, valine, leucine, methionine, lysine, phenylalanine, tyrosine, and tryptophan. Following addition/elimination, the resulting transoid α-(1′-fluoro)-β-(phenylsulfonyl)vinyl AA-esters undergo smooth sulfone-stannane interchange to stereoselectively give the corresponding transoid α-(1′-fluoro)-β-(tributylstannyl)vinyl AA-esters. Protodestannylation and global deprotection then yield these sterically encumbered and densely functionalized quaternary amino acids. The α-(1′-fluoro)vinyl trigger, a potential allene-generating functionality originally proposed by Abeles, is now available in a quaternary AA context for the first time. In an initial test of this new inhibitor class, α-(1′-fluoro)vinyllysine is seen to act as a time-dependent, irreversible inactivator of lysine decarboxylase from Hafnia alvei. The enantiomers of the inhibitor could be resolved, and each is seen to give time-dependent inactivation with this enzyme. Kitz-Wilson analysis reveals similar inactivation parameters for the two antipodes, L-α-(1′-fluoro)vinyllysine (Ki = 630 ± 20 μM; t1/2 = 2.8 min) and D-α-(1′-fluoro)vinyllysine (Ki = 470 ± 30 μM; t1/2 = 3.6 min). The stage is now set for exploration of the efficacy of this trigger in other PLP-enzyme active sites.

Ag2CO3/CA-AA-amidphos multifunctional catalysis in the enantioselective 1,3-dipolar cycloaddition of azomethine ylides

The new Ag2CO3/CA-AA-amidphos complexes have been demonstrated as highly efficient multifunctional catalysts in the asymmetric 1,3-dipolar cycloaddition of azomethine ylides. Under optimal conditions, highly functionalized endo-4 pyrrolidines were obtained with excellent yields (up to 99% yield) and enantioselectivities (up to 96% ee).

Stereospecific synthesis of pyrrolidines with varied configurations via 1,3-dipolar cycloadditions to sugar-derived enones

Enantiomerically pure pyrrolidines have been obtained by 1,3-dipolar cycloaddition of stabilized azomethine ylides and sugar enones (dihydropyranones) derived from pentoses. Thus, the S-enone (menthyl 3,4-dideoxy-(1S)-pent-3-enopyranosid-2-ulose) was prepared from d-xylose, while the R analogue was obtained from l-arabinose. The dipoles were generated in situ from α-arylimino esters of common amino acids (glycine, alanine, or phenylalanine) and aromatic aldehydes (benzaldehyde, 3-formylpyridine and 4-methoxybenzaldehyde). Under optimized conditions, the cycloaddition reactions were highly diastereo- and regioselective to yield, in most of the cases, a very major adduct of the 16 theoretically possible. The diastereoselectivity relies on the strict stereocontrol exerted by the stereogenic center of the pyranone. Thus, the (S)-enone, derived from d-xylose, gave tetrasubstituted pyrrolidines having a defined stereochemistry for the four stereocenters of the ring, while they had the opposite configuration when starting from the (R)-dihydropyranone. Furthermore, some endo-cycloadducts underwent isomerization of the carbons vicinal to the nitrogen atom to afford pyrrolidines with a rather unusual stereochemistry for the direct dipolar cycloadditions.

Diastereoselective synthesis of novel aza-diketopiperazines via a domino cyclohydrocarbonylation/addition process

Herein, we report an unprecedented, short and diastereo-selective synthesis of newly reported aza-diketopiperazine (aza-DKP) scaffolds starting from amino acids. The strategy is based on a Rh(i)-catalyzed hydroformylative cyclohydrocarbonylation of allyl-substituted aza-DKP, followed by a diastereoselective functionalization of the platform. This methodology allows the synthesis of novel bicyclic and tricyclic aza-DKP scaffolds incorporating six- or seven-membered rings, with potential applications in medicinal chemistry. This journal is the Partner Organisations 2014.

Synthesis of novel glycopeptidomimetics via Nβ-protected- amino alkyl isonitrile based Ugi 4C reaction

The Ugi-4C reaction employing Nβ-protected-amino alkyl isonitrile, amino acid ester, aldehyde, and glycosyl acid has resulted in novel glycosylated peptidomimetics. The extension of MCR products for the synthesis of N,N′-orthogonally protected

Combinatorial aid for underprivileged scaffolds: Solution and solid-phase strategies for a rapid and efficient access to novel aza-diketopiperazines (aza-DKP)

An efficient solution-phase synthesis of aza-diketopiperazines (aza-DKP, triazinediones) is reported. A structurally diverse collection of c-[aza-alkylGly-Pro] derivatives and yet unreported 2,4,5-trisubstituted-1,2,4- triazine-3,6-diones has been synthesized starting from Fmoc-l-Pro-OH and various Fmoc-l-amino acids. To extend the practical value of this class of dipeptidomimetics, a general solid-phase synthesis approach amenable to library production was developed on both Wang-PS and HMBA-PS resins. The final acidic treatment of the resins in TFA/water mixture at room temperature enabled the rapid and quantitative cyclization/release highly pure triazinediones. The conformational preferences and the spatial organization of the three substituents of a representative 2,4,5-trisubstituted-1,2,4-triazine-3,6-dione were investigated by X-ray diffraction and 1H NMR spectroscopy.