88612-90-2

Upstream product

• 100-42-5 styrene 
• 623-73-4 diazoacetic acid ethyl ester 
• 100-13-0 4-nitrostyrene 
• 586-78-7 para-nitrophenyl bromide 
• 946-38-3 cis-1-ethoxycarbonyl-2-phenylcyclopropane 
• 946-39-4 ethyl rac-(1S,2S)-2-phenylcycloproanecarboxylate 
• 186581-53-3 diazomethane 
• 555-16-8 4-nitrobenzaldehdye 

Downstream Products

• 1206479-02-8 ethyl 5-(4-nitrophenyl)-4,5-dihydroisoxazole-3-carboxylate 
• 159670-70-9 ethyl 5-(4-nitrophenyl)isoxazole-3-carboxylate 
• 16633-46-8 trans-2-(p-Nitrophenyl-)cyclopropanecarboxylic acid 
• 141794-89-0 (1R*,2R*)-ethyl 2-(4-aminophenyl)cyclopropanecarboxylate 
• 141794-89-0 ethyl cis-2-(p-aminophenyl)-1-cyclopropanecarboxylate 

Relevant academic research and scientific papers

QUINOLIN-4-ONE AND 4(1H)-CINNOLINONE COMPOUNDS AND METHODS OF USING SAME

The present disclosure relates to quinolin-4-one and 4(1H)-cinnolinone compounds and methods of using them to induce self-renewal of stem/progenitor supporting cells, including inducing the stem/progenitor cells to proliferate while maintaining, in the daughter cells, the capacity to differentiate into tissue cells.

Synthesis of Photosensitive Cyclopropane-Containing Polymers

New cyclopropyl methacrylate monomers were prepared, their radical polymerization was performed, and the composition and structure of the polymers obtained, containing reactive UV-sensitive fragments, were determined. Experiments on photochemical cross-li

Network topology and cavity confinement-controlled diastereoselectivity in cyclopropanation reactions catalyzed by porphyrin-based MOFs

In this work, we show that the stereoselectivity of a reaction can be controlled by directing groups of substrates, by network topology and by local cavity confinement of metal-organic framework (MOF) catalysts. We applied the porphyrin-based PCN-224(Rh), which contains no stereocenters in the cyclopropanation reaction using ethyl diazoacetate (EDA) as carbene source. When styrene and other non-coordinating olefins are used as substrates, high activity, but no diastereoselectivity is observed. Interestingly, conversion of 4-amino- and 4-hydroxystyrene substrates occurs with high diastereomeric ratios (dr) of up to 23 : 1 (trans : cis). We attribute this to local pore confinement effects as a result of substrate coordination to neighboring Rh-centers, which position the olefin with respect to the active site, causing a break of local symmetry of the coordinated substrate. The effect of local pore confinement was improved by using PCN-222(Rh) as catalyst, which is a structural analog of PCN-224(Rh) with characteristic Kagomé topology featuring shorter Rh-Rh distances. A remarkable dr of 42 : 1 (trans : cis) was observed for 4-aminostyrene. In this case, the length of the substrate corresponds to the average distance between two neighboring Rh centers within the pores of PCN-222(Rh), which drastically boosts the diastereoselectivity. This work showcases how diastereomeric control can be achieved by favorable substrate-catalyst interactions and thoughtful adjustment of confined reaction space using porphyrin-based MOFs, in which stereocenters are inherently absent.

Multigram Synthesis and C?C/C?N Couplings of Functionalized 1,2-Disubstituted Cyclopropyltrifluoroborates

A convenient approach to the multigram synthesis of functionalized 1,2-disubstituted cyclopropyltrifluoroborates was developed, based on Pd(II)- or Cu(I)-catalyzed reaction of vinyltrifluoroborate and diazo compounds. Optimized protocols allowed for the preparation of the target products as pure diastereomers on multigram scale. It was shown that the title compounds were good coupling partners for the Suzuki-Miyaura and Chan-Lam reactions, which provide medicinally relevant (het)arylcyclopropanes with high diastereoselectivity. (Figure presented.).

Engineering of RuMb: Toward a Green Catalyst for Carbene Insertion Reactions

The small, stable heme protein myoglobin (Mb) was modified through cofactor substitution and mutagenesis to develop a new catalyst for carbene transfer reactions. The native heme was removed from wild-type Mb and several Mb His64 mutants (H64D, H64A, H64V), and the resulting apoproteins were reconstituted with ruthenium mesoporphyrin IX (RuMpIX). The reconstituted proteins (RuMb) were characterized by UV-vis and circular dichroism spectroscopy and were used as catalysts for the N-H insertion of aniline derivatives and the cyclopropanation of styrene derivatives. The best catalysts for each reaction were able to achieve turnover numbers (TON) up to 520 for the N-H insertion of aniline, and 350 TON for the cyclopropanation of vinyl anisole. Our results show that RuMb is an effective catalyst for N-H insertion, with the potential to further increase the activity and stereoselectivity of the catalyst in future studies. Compared to native Mb ("FeMb"), RuMb is a more active catalyst for carbene transfer reactions, which leads to both heme and protein modification and degradation and, hence, to an overall much-reduced lifetime of the catalyst. This leads to lower TONs for RuMb compared to the iron-containing analogues. Strategies to overcome this limitation are discussed. Finally, comparison is also made to FeH64DMb and FeH64AMb, which have not been previously investigated for carbene transfer reactions.

Pure enantiomers of benzoylamino-tranylcypromine: LSD1 inhibition, gene modulation in human leukemia cells and effects on clonogenic potential of murine promyelocytic blasts

The pure enantiomers of the N-(2-, 3-, and 4-(2-aminocyclopropyl)phenyl)benzamides hydrochlorides 11a-j were prepared and tested against LSD1 and MAO enzymes. The evaluation of the regioisomers 11a-j highlighted a net increase of the anti-LSD1 potency by

A general mechanism for the copper- and silver-catalyzed olefin aziridination reactions: Concomitant involvement of the singlet and triplet pathways

The olefin aziridination reactions catalyzed by copper and silver complexes bearing hydrotris(pyrazolyl)borate (Tpx) ligands have been investigated from a mechanistic point of view. Several mechanistic probe reactions were carried out, specifically competition experiments with p-substituted styrenes, stereospecificity of olefins, effects of the radical inhibitors, and use of a radical clock. Data from these experiments seem to be contradictory, as they do not fully support the previously reported concerted or stepwise mechanisms. But theoretical calculations have provided the reaction profiles for both the silver and copper systems with different olefins to satisfy all experimental data. A mechanistic proposal has been made on the basis of the information that we collected from experimental and theoretical studies. In all cases, the reaction starts with the formation of a metal-nitrene species that holds some radical character, and therefore the aziridination reaction proceeds through the radical mechanism. The silver-based systems however hold a minimum energy crossing point (MECP) between the triplet and closed-shell singlet surfaces, which induce the direct formation of the aziridines, and stereochemistry of the olefin is retained. In the case of copper, a radical intermediate is formed, and this intermediate constitutes the starting point for competition steps involving ring-closure (through a MECP between the open-shell singlet and triplet surfaces) or carbon-carbon bond rotation, and explains the loss of stereochemistry with a given substrate. Overall, all the initially contradictory experimental data fit in a mechanistic proposal that involves both the singlet and the triplet pathways.

Biochemical, structural, and biological evaluation of tranylcypromine derivatives as inhibitors of histone demethylases LSD1 and LSD2

LSD1 and LSD2 histone demethylases are implicated in a number of physiological and pathological processes, ranging from tumorigenesis to herpes virus infection. A comprehensive structural, biochemical, and cellular study is presented here to probe the potential of these enzymes for epigenetic therapies. This approach employs tranylcypromine as a chemical scaffold for the design of novel demethylase inhibitors. This drug is a clinically validated antidepressant known to target monoamine oxidases A and B. These two flavoenzymes are structurally related to LSD1 and LSD2. Mechanistic and crystallographic studies of tranylcypromine inhibition reveal a lack of selectivity and differing covalent modifications of the FAD cofactor depending on the enantiomeric form. These findings are pharmacologically relevant, since tranylcypromine is currently administered as a racemic mixture. A large set of tranylcypromine analogues were synthesized and screened for inhibitory activities. We found that the common evolutionary origin of LSD and MAO enzymes, despite their unrelated functions and substrate specificities, is reflected in related ligand-binding properties. A few compounds with partial enzyme selectivity were identified. The biological activity of one of these new inhibitors was evaluated with a cellular model of acute promyelocytic leukemia chosen since its pathogenesis includes aberrant activities of several chromatin modifiers. Marked effects on cell differentiation and an unprecedented synergistic activity with antileukemia drugs were observed. These data demonstrate that these LSD1/2 inhibitors are of potential relevance for the treatment of promyelocytic leukemia and, more generally, as tools to alter chromatin state with promise of a block of tumor progression.

Cyclopropanation of olefins with diazo compounds catalyzed by a dicopper-substituted silicotungstate [γ-H2SiW 10O36Cu2(μ-1,1-N3) 2]4-

The dicopper-substituted γ-Keggin silicotungstate (TBA) 4[γ-H2SiW10O36Cu 2II(μ-1,1-N3)2] (I, TBA = tetra-n-butylammonium) could act as an efficient precatalyst for the chemoselective cylopropanation of olefins with diazo compounds. Various kinds of olefins were efficiently converted to the corresponding cyclopropane derivatives in good yields.

Reaction of esters of 2-arylcyclo-propanecarboxylic acids with nitrous acid. Synthesis of aryl-substituted 3-ethoxycarbonyl-4,5-dihydroisoxazoles and 3-ethoxycarbonylisoxazoles

Esters of 2-arylcyclopropanecarboxylic acids react with nitrous acid generated in situ with regioselective insertion of the nitrosyl cation into the cyclopropane ring. Depending on the substrate/nitrosylating agent ratio, the reaction proceeds with the formation of either aryl-substituted 3-ethoxycarbonyl-4,5-dihydroisoxazoles or the corresponding isoxazoles. The nature and position of the substituents in the aromatic ring of the starting 2-arylcyclopropanecarboxylic acid esters affect the reaction rate but have no effect on the regioselectivity of the attack by the nitrosyl cation on the three-membered ring. A dependence of the reactivity of isomeric substrates on their stereochemistry and position of the nitro group in the aromatic ring is noted for 2- and 4-nitrophenyl derivatives of esters of cis- and trans-2-arylcyclopropanecarboxylic acids.