40216-71-5

Upstream product

• 100-52-7 benzaldehyde 
• 67-56-1 methanol 
• 25616-13-1 alanine hydrochloride 
• 13515-97-4 methyl 2-aminopropanoate monohydrochloride 
• 7625-53-8 rac-Ala-OMe 
• 2491-20-5 L-alanine methyl ester hydrochloride 
• 10065-72-2 L-Alanine methyl ester 

Downstream Products

• 48047-94-5 α-Methylornithin 
• 113273-75-9 methyl (1SR,3RS,3aSR,6aRS)-1,5-dimethyl-4,6-dioxo-3-phenyloctahydropyrrolo[3,4-c]pyrrole-1-carboxylate 
• 111396-01-1 4-Benzoyl-3-(4-chloro-phenyl)-2-methyl-5-phenyl-pyrrolidine-2-carboxylic acid methyl ester 
• 80597-75-7 (2R,4R,5R)-2-Methyl-5-phenyl-1-aza-bicyclo[2.1.0]pentane-2,4-dicarboxylic acid 4-ethyl ester 2-methyl ester 
• 104706-74-3 (1R,2R,3R)-2-(1-Methoxycarbonyl-1-{[1-phenyl-meth-(E)-ylidene]-amino}-ethyl)-3-methyl-cyclopropanecarboxylic acid methyl ester 
• 104706-76-5 (E)-5-Methyl-5-{[1-phenyl-meth-(E)-ylidene]-amino}-hex-2-enedioic acid dimethyl ester 
• 104706-72-1 (1R,2R)-2-(1-Methoxycarbonyl-1-{[1-phenyl-meth-(E)-ylidene]-amino}-ethyl)-cyclopropanecarboxylic acid methyl ester 
• 101235-90-9 (2R,4R,5R)-4-Cyano-2-methyl-5-phenyl-1-aza-bicyclo[2.1.0]pentane-2-carboxylic acid methyl ester 
• 101235-84-1 4-Bromo-4-cyano-2-methyl-5-phenyl-pyrrolidine-2-carboxylic acid methyl ester 
• 73838-97-8 Dimethyl (Z)-2-(benzylideneamino)-2-methylpent-3-ene-2,5-dioate 
• 73838-90-1 Dimethyl (E)-2-(benzylideneamino)-2-methylpent-3-ene-2,5-dioate 
• 73838-92-3 Methyl (E)-2-(benzylideneamino)-2-methyl-4-cyanobut-3-enoate 
• 103897-58-1 5-Chloro-2-methyl-2-{[1-phenyl-meth-(E)-ylidene]-amino}-pentanoic acid methyl ester 
• 64298-96-0 dimethyl 2-(benzylideneamino)-2-methylpentanedioate 

Relevant academic research and scientific papers

Boron Dipyrromethene (BODIPY) as Electron-Withdrawing Group in Asymmetric Copper-Catalyzed [3+2] Cycloadditions for the Synthesis of Pyrrolidine-Based Biological Sensors

In this work, we describe the use of Boron Dipyrromethene (BODIPY) as electron-withdrawing group for activation of double bonds in asymmetric copper-catalyzed [3+2] cycloaddition reactions with azomethine ylides. The reactions take place under smooth conditions and with high enantiomeric excess for a large number of different substituents, pointing out the high activation of the alkene by using a boron dipyrromethene as electron-withdrawing group. Experimental, theoretical studies and comparison with other common electron-withdrawing groups in asymmetric copper-catalyzed [3+2] cycloadditions show the reasons of the different reactivity of the boron dipyrromethene derivatives, which can be exploited as a useful activating group in asymmetric catalysis. Additional experiments show that the so obtained pyrrolidines can be employed as biocompatible biosensors, which can be located in the endosomal compartments and do not present toxicity in three cell lines. (Figure presented.).

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.

Discovery of CRBN E3 Ligase Modulator CC-92480 for the Treatment of Relapsed and Refractory Multiple Myeloma

Many patients with multiple myeloma (MM) initially respond to treatment with modern combination regimens including immunomodulatory agents (lenalidomide and pomalidomide) and proteasome inhibitors. However, some patients lack an initial response to therapy (i.e., are refractory), and although the mean survival of MM patients has more than doubled in recent years, most patients will eventually relapse. To address this need, we explored the potential of novel cereblon E3 ligase modulators (CELMoDs) for the treatment of patients with relapsed or refractory multiple myeloma (RRMM). We found that optimization beyond potency of degradation, including degradation efficiency and kinetics, could provide efficacy in a lenalidomide-resistant setting. Guided by both phenotypic and protein degradation data, we describe a series of CELMoDs for the treatment of RRMM, culminating in the discovery of CC-92480, a novel protein degrader and the first CELMoD to enter clinical development that was specifically designed for efficient and rapid protein degradation kinetics.

Study of 1,3-dipolar cycloaddition of amino-acid azomethines and Juglone

Novel 2,3,4,9-tetrahydro- and 4,9-dihydro-1H-benzo[f]isoindole derivatives were synthesized from Juglone and amino-acid azomethines in 74–85% yields via 1,3-dipolar cycloaddition. The stereo- and regioselectivity of cycloaddition was confirmed by NMR spec

Synthesis and Electrochemical Estimation of DNA-Binding Capacity of Novel Ferrocene-Containing Pyrrolidines

The design, synthesis, spectral and electrochemical characterization of a series of novel pyrrolidine derivatives have been described. The synthesis was achieved by 1,3-dipolar cycloaddition of azomethine ylides and ferrocene-substituted chalcones, while

Synthesis of novel multi-functionalized pyrrolidines by [3 + 2] dipolar cycloaddition of azomethine ylides and vinyl ketones

Abstract: An efficient and easy synthetic route to substituted pyrrolidine derivatives has been established through [3 + 2] dipolar cycloaddition of vinyl ketones and azomethine ylides. The reactions proceed smoothly, under mild conditions, affording mode

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

Stereoselective and Site-Specific Allylic Alkylation of Amino Acids and Small Peptides via a Pd/Cu Dual Catalysis

We report a stereoselective and site-specific allylic alkylation of Schiff base activated amino acids and small peptides via a Pd/Cu dual catalysis. A range of noncoded α,α-dialkyl α-amino acids were easily synthesized in high yields and with excellent enantioselectivities (up to >99% ee). Furthermore, a direct and highly stereoselective synthesis of small peptides with enantiopure α-alkyl or α,α-dialkyl α-amino acids residues incorporated at specific sites was accomplished using this dual catalyst system.

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).