319-61-9

Upstream product

• 16652-71-4 benzyl (2S)-2-pyrrolidinecarboxylate hydrochloride 
• 383-63-1 ethyl trifluoroacetate, 
• 147-85-3 L-proline 
• 407-25-0 trifluoroacetic anhydride 

Downstream Products

• 36724-68-2 (S)-N-trifluoroacetylproline acid chloride 
• 97589-54-3 (S)-1-(2-benzoylpyrrolidin-1-yl)-2,2,2-trifluoroethan-1-one 
• 848073-25-6 2,2,2-Trifluoro-1-[(S)-2-(3-methoxy-benzoyl)-pyrrolidin-1-yl]-ethanone 
• 172926-95-3 (S)-2-(3,4-dimethoxybenzyl)pyrrolidine 
• 848073-35-8 Dimethyl-(4-(S)-1-pyrrolidin-2-ylmethyl-phenyl)-amine 
• 848073-19-8 C₁₉H₁₇F₃NO₄P 
• 119580-41-5 (S)-(+)-2-(trifluoromethyl)pyrrolidine 
• 482-20-2 (S)-(+)-tylophorine 
• 122502-83-4 (+/-)-2-(2,5-dimethoxy-2-methylbenzoyl)-1-(trifluoroacetyl)pyrrolidine 
• 122502-84-5 1-[2-(2,5-Dihydroxy-4-methyl-benzoyl)-pyrrolidin-1-yl]-2,2,2-trifluoro-ethanone 
• 910618-48-3 α-(2,5-dimethoxy-4-methylphenyl)-2-pyrrolidinemethanol 
• 3847-66-3 (S)-2-anilinocarbonyl-1-trifluoroacetylpyrrolidine 

Relevant academic research and scientific papers

DNA Barcoding a Complete Matrix of Stereoisomeric Small Molecules

It is challenging to incorporate stereochemical diversity and topographic complexity into DNA-encoded libraries (DELs) because DEL syntheses cannot fully exploit the capabilities of modern synthetic organic chemistry. Here, we describe the design, construction, and validation of DOS-DEL-1, a library of 107 616 DNA-barcoded chiral 2,3-disubsituted azetidines and pyrrolidines. We used stereospecific C-H arylation chemistry to furnish complex scaffolds primed for DEL synthesis, and we developed an improved on-DNA Suzuki reaction to maximize library quality. We then studied both the structural diversity of the library and the physicochemical properties of individual compounds using Tanimoto multifusion similarity analysis, among other techniques. These analyses revealed not only that most DOS-DEL-1 members have "drug-like" properties, but also that the library more closely resembles compound collections derived from diversity synthesis than those from other sources (e.g., commercial vendors). Finally, we performed validation screens against horseradish peroxidase and carbonic anhydrase IX, and we developed a novel, Poisson-based statistical framework to analyze the results. A set of assay positives were successfully translated into potent carbonic anhydrase inhibitors (IC50 = 20.1-68.7 nM), which confirmed the success of the synthesis and screening procedures. These results establish a strategy to synthesize DELs with scaffold-based stereochemical diversity and complexity that does not require the development of novel DNA-compatible chemistry.

TFA-protected α-amino acid N-hydroxysuccinimide ester: Application for inter- And intramolecular acylation

The utilization of N-trifluoroacetyl (TFA)-α-amino acid N-hydroxysuccinimide ester (OSu) derivatives, a promising acylating agent with high storage stability, is reported for Friedel-Crafts acylation into arenes and N-heterocycles. The reaction between TF

Synthesis of a Bicyclic Azetidine with in Vivo Antimalarial Activity Enabled by Stereospecific, Directed C(sp3)-H Arylation

The development of new antimalarial therapeutics is necessary to address the increasing resistance to current drugs. Bicyclic azetidines targeting Plasmodium falciparum phenylalanyl-tRNA synthetase comprise one promising new class of antimalarials, especially due to their activities against three stages of the parasite's life cycle, but a lengthy synthetic route to these compounds may affect the feasibility of delivering new therapeutic agents within the cost constraints of antimalarial drugs. Here, we report an efficient synthesis of antimalarial compound BRD3914 (EC50 = 15 nM) that hinges on a Pd-catalyzed, directed C(sp3)-H arylation of azetidines at the C3 position. This newly developed protocol exhibits a broad substrate scope and provides access to valuable, stereochemically defined building blocks. BRD3914 was evaluated in P. falciparum-infected mice, providing a cure after four oral doses.

Modulating hydrogen-bond basicity within the context of protein-ligand binding: A case study with thrombin inhibitors that?reveals a dominating role for desolvation

Understanding subtle aspects of hydrogen bonding is a challenging but crucial task to improve our ability to design ligands with high affinity for protein hosts. To gain a deeper understanding of these aspects, we investigated a series of thrombin inhibitors in which the basicity of the ligand's group that accepts an H-bond from Gly216 was modulated via bioisosterism; e.g., a C=O acceptor was made electron deficient or rich via bioisosteric replacements of the adjacent moiety. Although the ligand's binding affinity was anticipated to improve when the H-bond basicity is increased (due to stronger H-bonding with the protein), we herein present data that unexpectedly revealed an opposite trend. This trend was attributed to a dominating role played by desolvation in determining the relative binding affinity. For example, a decrease in the H-bond basicity reduces the desolvation penalty and, as experimentally observed, improves the binding affinity, given that the reduction in the desolvation penalty dominates the change in the net contribution of the ligand's interactions with the protein. The current study, therefore, reveals that desolvation can be a major underlying cause for the apparently counterintuitive structure-activity relationship (SAR) outcomes, and indicates that understanding this factor can improve our ability to predict binding affinity and to design more potent ligands.

Discovery and structure-activity relationships of 2-benzylpyrrolidine- substituted aryloxypropanols as calcium-sensing receptor antagonists

A structure-activity relationship study of the amine portion of the calcilytic compound NPS-2143 resulted in the discovery of substituted 2-benzylpyrrolidines as replacements for the 1,1-dimethyl-2-naphthalen-2-yl- ethylamine. When compared to NPS-2143, a

Use of N-trifluoroacetyl-protected amino acid chlorides in peptide coupling reactions with virtually complete preservation of stereochemistry

The use of protected amino acid chlorides for peptide coupling reactions has long been avoided due to the extensive racemization that commonly occurs during either the acid chloride formation or the coupling reaction itself. Conditions are described which

Rearrangement of ammonium ylides produced by intramolecular reaction of catalytically generated metal carbenoids. Part 2. Stereoselective synthesis of bicyclic amines

Ammonium ylides produced by intramolecular reaction of copper carbenoids tethered to cyclic allylic amines undergo [2,3]-rearrangement to deliver bicyclic amines. The reaction can be performed using a cyclic N-allylamine in which the diazo group is tethered adjacent to nitrogen, or a vinyl-substituted cyclic amine in which the diazo group is N-tethered to the ring. In the former type of reaction, stereoselective ylide formation and rearrangement usually delivers high levels of diastereocontrol. In the latter case, efficient 'chirality transfer' can be accomplished when the reaction is performed using an enantiomerically pure substrate. The reactions have been used to construct pyrrolizidine, indolizidine and quinolizidine systems, and the CE sub-unit found in the manzamine and ircinal alkaloids.

A parallel preparation of a bicyclic N-chiral amine library and its use for chiral catalyst screening

A parallel library of optically active bicyclic tertiary amines bearing N-chiral bridgehead nitrogen atoms was readily prepared by condensation of primary amines, cyclic amino acids and aldehydes. The enantiocontrolling ability of each of the library members was examined for the asymmetric alkylation of benzaldehyde with diethylzinc, and (3R,6R,7aS)-(2,3-diphenyl-6-hydroxy)hexahydro-1H-pyrrolo[1,2-c]imidazol-1- one, which contains a β-amino alcohol unit, showed high enantioselectivity.

Preparation of both enantiomers of 1-allyl-1,2,3,4-tetrahydro-β-carboline using allyltin reagents and a chiral auxiliary derived from L-proline

β-Carboline, which had an acyl group derived from L-proline at the 9-position, reacted with allyltributyltin and 2,2,2-trichloroethyl chloroformate to afford an 1-allyl-1,2-dihydro-β-carboline derivative in a diastereoselective manner. The chiral acyl group at N-9 was readily eliminated by aqueous alkali to give a corresponding carboxylic acid. The formed 1-allyl-1,2-dihydro-β-carboline was transformed via two reduction steps to 1-allyl-1,2,3,4-tetrahydro-β-carboline in high ee. When the allylation was carried out using tetraallyltin instead of allyltributyltin, the stereoselectivity was reversed, and the antipode of the allyl adduct was obtained in high yield and ee in the presence of tin(IV) tetraiodide. Thus, it was found that both enantiomers of 1-allyl-β-carboline were obtained in good enantioselectivities by the use of the same chiral auxiliary.

Asymmetric Synthesis of Optically Active threo- and erythro-Pyrrolidinylbenzyl Alcohol by the Highly Stereospecific Arylation of (S)-Proline and the Subsequent Highly Diastereoselective Reduction of the α-Amino Ketone

Optically active α-amino phenyl ketones in 92-94percent enantiomeric excess (e.e.) were obtained from the stereospecific arylation of (S)-proline or its derivatives by Friedel-Crafts reaction of by Grignard reaction.The subsequent complementary diastereoselective reductions of the α-amino ketone afforded respectively (S)- and (R)-α-benzyl alcohol in 93-100percent e.e. and in 100percent diastereoisomeric excess.The stereochemical course of the reduction of the α-amino ketone is discussed.