335593-39-0

Upstream product

• 623-73-4 diazoacetic acid ethyl ester 
• 98-83-9 isopropenylbenzene 

Downstream Products

• 82095-92-9 (1S,2S)-2-carboxy-1-methyl-1-phenylcyclopropane 
• 82095-93-0 (1R,2R)-2-methyl-2-phenylcyclopropane-1-carboxylic acid 
• 29161-85-1 (1R, 2R)-2-methyl-2-phenylcyclopropanecarboxamide 

Relevant academic research and scientific papers

Controllable stereoinversion in DNA-catalyzed olefin cyclopropanationviacofactor modification

The assembly of DNA with metal-complex cofactors can form promising biocatalysts for asymmetric reactions, although catalytic performance is typically limited by low enantioselectivities and stereo-control remains a challenge. Here, we engineer G-quadruplex-based DNA biocatalysts for an asymmetric cyclopropanation reaction, achieving enantiomeric excess (eetrans) values of up to +91% with controllable stereoinversion, where the enantioselectivity switches to ?72% eetransthrough modification of the Fe-porphyrin cofactor. Complementary circular dichroism, nuclear magnetic resonance, and fluorescence titration experiments show that the porphyrin ligand of the cofactor participates in the regulation of the catalytic enantioselectivityviaa synergetic effect with DNA residues at the active site. These findings underline the important role of cofactor modification in DNA catalysis and thus pave the way for the rational engineering of DNA-based biocatalysts.

Semi-Rationally Designed Short Peptides Self-Assemble and Bind Hemin to Promote Cyclopropanation

The self-assembly of short peptides gives rise to versatile nanoassemblies capable of promoting efficient catalysis. We have semi-rationally designed a series of seven-residue peptides that form hemin-binding catalytic amyloids to facilitate enantioselect

Synthesis of Forms of a Chiral Ruthenium Complex Containing a Ru-Colefin(sp2) Bond and Their Application to Catalytic Asymmetric Cyclopropanation Reactions

Organometallic complexes [Ru-Colefin(sp2)-Ru(II)-Pheox 2a-2d] containing a Ru-Colefin(sp2) bond have been prepared from unsaturated chiral oxazoline derivatives and evaluated for asymmetric cyclopropanation reactions. The corresponding optically active cyclopropanes were obtained with high yields and high stereoselectivities (≥99/2) bond. In particular, Ru(II)-Prox catalyst 2c, in which there was no geminal substituent on the metal, was shown to have the highest enantioselectivities.

OPIOID RECEPTOR MODULATORS AND PRODUCTS AND METHODS RELATED THERETO

Compounds are provided having the structure of Formula (I): or a pharmaceutically acceptable isomer, racemate, hydrate, solvate, isotope, or salt thereof, wherein A, B, L, R3, R4, R5, R6, R8, m and n are as defined herein. Such compounds modulate the opioid receptor, particulare the mu-opioid receptor (MOR) and/or the kappa-opioid receptor (KOR), and/or the delta-opioid receptor (DOR). Products containing such compounds, as well as methods for their use and preparation, are also provided.

Gram-Scale Synthesis of Chiral Cyclopropane-Containing Drugs and Drug Precursors with Engineered Myoglobin Catalysts Featuring Complementary Stereoselectivity

Engineered hemoproteins have recently emerged as promising systems for promoting asymmetric cyclopropanations, but variants featuring predictable, complementary stereoselectivity in these reactions have remained elusive. In this study, a rationally driven strategy was implemented and applied to engineer myoglobin variants capable of providing access to 1-carboxy-2-aryl-cyclopropanes with high trans-(1R,2R) selectivity and catalytic activity. The stereoselectivity of these cyclopropanation biocatalysts complements that of trans-(1S,2S)-selective variants developed here and previously. In combination with whole-cell biotransformations, these stereocomplementary biocatalysts enabled the multigram synthesis of the chiral cyclopropane core of four drugs (Tranylcypromine, Tasimelteon, Ticagrelor, and a TRPV1 inhibitor) in high yield and with excellent diastereo- and enantioselectivity (98–99.9% de; 96–99.9% ee). These biocatalytic strategies outperform currently available methods to produce these drugs.

Non-covalent immobilization of chiral copper complexes on Al-MCM41: Effect of the nature of the ligand

Cu-Al-MCM41, prepared by deposition of copper(II) triflate with incipient wetness impregnation and thermal treatment under air flow, can be modified with different chiral ligands of the bis(oxazoline) family. The efficiency of the supported chiral catalysts in the enantioselective cyclopropanation of styrenes with ethyl diazoacetate depends on the nature of the ligand. The azabis(oxazolines) perform much better than the bis(oxazolines) and give stable catalysts that can be used for at least five consecutive runs, with productivities that can reach values close to 1000 molecules of cyclopropane per copper site. The best enantioselectivities obtained with these catalysts are in the range of 60-70% ee in the reaction at 90 °C.

Highly diastereoselective and enantioselective olefin cyclopropanation using engineered myoglobin-based catalysts

Using rational design, an engineered myoglobinbased catalyst capable of catalyzing the cyclopropanation of aryl-substituted olefins with catalytic proficiency (up to 46800 turnovers) and excellent diastereo- and enantioselectivity (98-99.9%) was developed. This transformation could be carried out in the presence of up to 20 gL-1 olefin substrate with no loss in diastereo- and/or enantioselectivity. Mutagenesis and mechanistic studies support a cyclopropanation mechanism mediated by an electrophilic, heme-bound carbene species and a model is provided to rationalize the stereopreference of the protein catalyst. This work shows that myoglobin constitutes a promising and robust scaffold for the development of biocatalysts with carbene-transfer reactivity.

Continuous flow asymmetric cyclopropanation reactions using Cu(i) complexes of Pc-L* ligands supported on silica as catalysts with carbon dioxide as a carrier

Continuous flow heterogeneous asymmetric cyclopropanations catalysed by supported hydrogen-bonded (SHB) chiral copper(i) complexes of pyridine containing tetraazamacrocyclic ligands Pc-L* using CO2 as a transport vector are described. The catalytic system showed high stability and good recyclability without loss of activity for at least 24 h in CO2 and catalyst turnover numbers up to 440 were obtained with excellent conversion (up to 99%) and high selectivity (up to 88%). No leaching of copper was observed. Cyclopropane products from both aromatic and aliphatic olefins were obtained in good yields with enantiomeric excesses up to 72%. This journal is the Partner Organisations 2014.

A new cobalt-salen catalyst for asymmetric cyclopropanation. Synthesis of the serotonin-norepinephrine repuptake inhibitor (+)-synosutine

A new C2 symmetric cobalt(II)-salen catalyst based on cis-2,5-diaminobicyclo[2.2.2]octane as the chiral scaffold was prepared which, in the presence of potassium thioacetate as the promoter, catalyzed the formation of cyclopropanes from 1,1-dis

First pre-functionalised polymeric aromatic framework from mononitrotetrakis(iodophenyl)methane and its applications

Starting from mononitrotetrakis(iodophenyl)methane as monomer, we report the preparation of the first pre-functionalised porous aromatic frameworks (PAFs) and their application as supports for organometallic catalysts. Neutral coordinate imino-pyridine Schiff base (PAF-NPy) or chiral bis-amino (PAF-NPro) ligands were obtained by post-synthetic treatment of PAF-NH2 and treated with copper(I) or rhodium(I) to yield the corresponding supported transition-metal catalysts. The as-prepared PAF-NN-M catalysts exhibited activity and selectivity similar to that of the corresponding homogeneous catalysts and were easily removed from reaction media and recycled without loss of activity or selectivity. New copper catalysts: The preparation of pre-functionalised porous aromatic frameworks (PAFs) and their application as supports for organometallic catalysts (see figure) is reported for the first time.