748149-61-3

Upstream product

• 15761-39-4 1-(tert-butoxycarbonyl)-L-proline 
• 91-00-9 Benzhydrylamine 
• 1148-11-4 N-Benzyloxycarbonyl-L-proline 
• 141874-26-2 N-Boc-(S)-proline chloride 
• 84890-94-8 (S)-2-Isobutoxycarbonyloxycarbonyl-pyrrolidine-1-carboxylic acid tert-butyl ester 
• 212699-49-5 benzyloxycarbonyl-L-proline diphenylmethylamide 

Downstream Products

• 1004960-65-9 (2S,2'S)-1,1'-(2-hydroxy-5-methyl-1,3-phenylene)bis(methylene)bis(N-benzhydrylpyrrolidine-2-carboxamide) 

Relevant academic research and scientific papers

Trans-4-Hydroxy-l-prolinamide as an efficient catalyst for direct asymmetric aldol reaction of acetone with isatins

Prolinamide (2S,4R)-4-hydroxy-N-((S)-1-phenylethyl)pyrrolidine-2-carboxamide was found to be an efficient organocatalyst (10 mol %) for the direct asymmetric aldol reactions of isatins with acetone at -35 °C in THF and afforded the product in 79% yield wi

Asymmetric Three-Component Reaction for the Synthesis of Tetrasubstituted Allenoates via Allenoate-Copper Intermediates

We developed an efficient and direct route for the synthesis of tetrasubstituted allenes via asymmetric multicomponent reaction (AMCR) by utilizing a variety of α-diazoesters, terminal alkynes, and isatins. This method enables Cu(I)-involved AMCRs of α-diazo compounds and also gives solid experimental evidence for the formation of allenoate-Cu(I) intermediates in C–H insertion of α-diazoesters to terminal alkynes. Combined-acid systems of guanidinylated metal complexes lead to higher reactivity and equally effective asymmetric environment. A catalytic asymmetric three-component reaction of α-diazoesters with terminal alkynes and isatins was achieved. This one-pot synthesis gave rise to axially chiral tetrasubstituted allenoates bearing a stereogenic center. The chiral guanidinium salt/CuBr/YBr3 catalytic system proved efficient and highly diastereo- and enantioselective for a wide range of alkynes, aromatic α-diazoesters, and isatins under mild reaction conditions. This approach enables a Cu(I)-involved asymmetric multicomponent reaction (AMCR) of α-diazo compounds and gives solid experimental evidence for the formation of allenoate-Cu(I) intermediates in C–H insertion of α-diazoesters to terminal alkynes. We also found that additional acids improved the catalyst efficiency of guanidinium salt/CuCl in the direct enantioselective C–H insertion of α-aryl diazoesters. Mechanism studies suggest that the combined-acid systems (Lewis acid combined with assisted Lewis acid or Br?nsted acid combined with assisted Lewis acid) bring out higher reactivity by associative interaction and allow for an equally effective asymmetric environment. Chirality is a universal phenomenon found in nature. Different from the usual central chirality, allenes are a class of compounds bearing three-carbon axially chiral skeletons and have attracted increasing attention for their usefulness as synthetic intermediates. This unique structural feature can provide allenes with specific biological activity and has been found in many drug molecules and natural products; thus, there is increasing demand for new routes toward these pharmaceutically relevant compounds. Nevertheless, the catalytic asymmetric synthesis of axially chiral allenes, especially for tetrasubstituted ones, is still in its infancy. Here, we report the synthesis of tetrasubstituted allenoates via an asymmetric three-component reaction of α-diazoesters with terminal alkynes and isatins. This gives access to the desired central and axial chirality bearing carbinol allenoate by trapping the corresponding allenoate-copper intermediate with isatin.

Synthesis and anticancer activity of conformationally constrained Smac mimetics containing pseudo β turns

Herein, we report synthesis and in vitro anticancer activity of conformationally constrained Smac mimetics containing reverse turn inducing motifs “Ant-Pro” and “sAnt-Pro”. The synthesis of Smac analogs with diverse hydrophobic groups at the C-

Aromatic l-prolinamide-catalyzed asymmetric Michael addition of aldehydes to nitroalkenes

Two chiral aromatic l-prolinamides were synthesized in high overall yield (95%) from N-Boc-l-proline and served as organocatalysts in asymmetric Michael reactions of aldehydes to nitroalkenes. Under the optimized reaction conditions, (S)-N-tritylpyrrolidi

Asymmetric synthesis of cis-4-aminobenzopyran derivatives catalyzed by N,N′-Dioxide-Sc(OTf)3 complexes

The reactions of salicylaldimines with electron-rich alkenes (2,3-dihydro-2H-furan and 3,4-dihydro-2H-pyran) catalyzed by N,N′-dioxide-Sc(OTf)3 complexes were investigated. The methodology was successfully applied to the asymmetric synthesis of

Chiral bisformamides as effective organocatalysts for the asymmetric one-pot, three-component strecker reaction

(Chemical Equation Presented) C2-symmetric chiral bisformamides have been shown to catalyze the asymmetric one-pot, three-component Strecker reaction, which produced the α-amino nitriles in excellent yields (up to 99%) with good enantioselectiv

Catalytic asymmetric cyano-ethoxycarbonylation reaction of aldehydes using a novel C2-symmetric chiral N,N′-dioxide titanium complex

The asymmetric addition of ethyl cyanoformate to a range of aldehydes was efficiently catalyzed by a easily prepared C2-symmetric chiral N,N′-dioxide-Ti(IV) complex in high yields with up to 90% ee under mild conditions. A linear effect between

Asymmetric cyanosilylation of aldehydes catalyzed by novel organocatalysts

A novel proline-based N,N′-dioxide, which is easily prepared from inexpensive chemicals, serves as an effective catalyst for enantioselective cyanosilylation of aldehydes in up to 73% ee. Georg Thieme Verlag Stuttgart.

2-Nitrophenylcarbamoyl-(S)-prolyl-(S)-3-(2-naphthyl)alanyl-N-benzyl-N- methylamide (SDZ NKT 343), a potent human NK1 tachykinin receptor antagonist with good oral analgesic activity in chronic pain models

A lead compound which had sub-micromolar affinity for the rabbit NK1 receptor but negligible affinity for rat NK1 receptors, 3a, was discovered by directed screening. 2-Substitution in the ring of the benzylthiourea substituent in the initial lead was found to be important, and halogens (Cl, Br) in this position were found to improve affinity for the human receptor. The activity of a series of 2-halo-substituted benzylthioureas was then optimized by modification of the proline diphenylmethyl amide, guided by a simple conceptual model based on structural overlay between these early antagonists and NK1 selective peptides. In this way, aromatic amino acid amides were identified which had improved affinity with respect to the starting diphenylmethyl (DPM) amides. The first sub-nanomolar ligand for the human NK1 receptor which arose from this series, 4af, combined a 2- chlorobenzylthiourea unit with a 2-naphthylalanine amide. Contemporaneously it was discovered that the benzylthiourea unit could be simplified to a phenylthiourea providing that an appropriate 2-substituent was also incorporated. Combination of these two series gave 2-NO2 phenylthiourea analogues which led directly to the analogous urea, 5f (2- nitrophenylcarbamoyl-(S)-prolyl-(S)-3-(2-naphthyl)alanyl-N-benzy-N- methylamide, SDZ NKT 343), a highly potent ligand for the human NK1 receptor (K(i) = 0.16 nM). In addition to its high in vitro potency, 5f proved to be a potent orally active analgesic in guinea pig models of chronic inflammatory and neuropathic pain. The nature of the 2-aryl substituent was found to be critical for oral activity in this series. Clinical evaluation of 5f as a novel analgesic agent is currently underway.