762247-01-8

Upstream product

• 125617-18-7 3-(4-trifluoromethylphenyl)-2-propen-1-ol 
• 173546-21-9 3-(4-trifluoromethylphenyl)prop-2-yn-1-ol 
• 95123-61-8 (2E)-3-(4-trifluoromethylphenyl)prop-2-enal 
• 455-13-0 4-Iodobenzotrifluoride 
• 2062-26-2 3-<4'-(trifluoromethyl)phenyl>-2-propenoic acid 
• 101466-85-7 ethyl (E)-4-trifluoromethylcinnamate 
• 455-19-6 4-Trifluoromethylbenzaldehyde 
• 149946-79-2 1-(4'-(trifluoromethyl)phenyl)-allylalcohol 

Downstream Products

• 1214913-11-7 [1-(4-trifluoromethylphenyl)allyl]dimethylphenylsilane 
• 1214913-15-1 (E)-dimethyl(phenyl)(3-(4-(trifluoromethyl)phenyl)allyl)silane 
• 1375536-73-4 (E)-4,4,5,5-tetramethyl-2-(4-(4-(trifluoromethyl)phenyl)but-3-en-1-yl)-1,3,2-dioxaborolane 
• 1417719-52-8 (1S,2S,3R)-methyl 2-(4-(trifluoromethyl)phenyl)bicyclo[1.1.0]butane-1-carboxylate 
• 1417719-43-7 (E)-methyl 2-diazo-5-(4-(trifluoromethyl)phenyl)pent-4-enoate 
• 1417719-36-8 C₁₅H₁₅F₃O₃ 
• 1583276-50-9 (1Z,4E)-2,2-dimethyl-1-phenyl-5-(4-(trifluoromethyl)phenyl)pent-4-en-1-one oxime 
• 1583276-29-2 4,4-dimethyl-5-phenyl-2-(4-(trifluoromethyl)benzyl)-3,4-dihydro-2H-pyrrole 1-oxide 
• 1581720-42-4 (2S,3S)-N-benzyl-2-(dimethylamino)-3-(4-(trifluoromethyl)phenyl)pent-4-enamide 
• 1581720-59-3 (E)-N,N-dimethyl-3-(4-(trifluoromethyl)phenyl)prop-2-en-1-amine 
• 1464149-45-8 (E)-(trifluoromethyl)(3-(4-(trifluoromethyl)phenyl)allyl)sulfane 

Relevant academic research and scientific papers

Enantioselective Allenoate-Claisen Rearrangement Using Chiral Phosphate Catalysts

Herein we report the first highly enantioselective allenoate-Claisen rearrangement using doubly axially chiral phosphate sodium salts as catalysts. This synthetic method provides access to β-amino acid derivatives with vicinal stereocenters in up to 95percent ee. We also investigated the mechanism of enantioinduction by transition state (TS) computations with DFT as well as statistical modeling of the relationship between selectivity and the molecular features of both the catalyst and substrate. The mutual interactions of charge-separated regions in both the zwitterionic intermediate generated by reaction of an amine to the allenoate and the Na+-salt of the chiral phosphate leads to an orientation of the TS in the catalytic pocket that maximizes favorable noncovalent interactions. Crucial arene-arene interactions at the periphery of the catalyst lead to a differentiation of the TS diastereomers. These interactions were interrogated using DFT calculations and validated through statistical modeling of parameters describing noncovalent interactions.

P-Chiral Monophosphorus Ligands for Asymmetric Copper-Catalyzed Allylic Alkylation

Asymmetric copper-catalyzed allylic alkylation between allyl bromides and alkyl Grignard reagents using a P-chiral monophosphorus ligand is described. A range of terminal olefins bearing tertiary or quaternary carbon centers were formed in good branched/linear selectivities and excellent enantioselectivities at copper loadings as low as 0.5 mol %.

Ruthenium-catalyzed enantioselective C-H functionalization: A practical access to optically active indoline derivatives

Ru(II)-catalyzed enantioselective C-H activation/hydroarylation has been developed for the first time, allowing for highly enantioselective synthesis of indoline derivatives via catalytic C-H activation. Commercially available Ru(II) arene complexes and chiral α-methylamines were employed as highly enantioselective catalysts. Based on a sterically rigidified chiral transient directing group, multisubstituted indolines were produced in up to 92% yield with 96% ee. Further transformation of the resulting 4-formylindoline enables access to an optically active tricyclic compound that is of potential biological and pharmaceutical interest.

Discovery of novel piperonyl derivatives as diapophytoene desaturase inhibitors for the treatment of methicillin-, vancomycin- and linezolid-resistant Staphylococcus aureus infections

Inhibition of S. aureus diapophytoene desaturase (CrtN) could serve as an alternative approach for addressing the tricky antibiotic resistance by blocking the biosynthesis of carotenoid pigment which shields the bacterium from host oxidant killing. In this study, we designed and synthesized 44 derivatives with piperonyl scaffold targeting CrtN and the structure-activity relationships (SARs) were examined extensively to bring out the discovery of 21b with potent efficacy and better hERG safety profile compared to the first class CrtN inhibitor benzocycloalkane derivative 2. Except the excellent pigment inhibitory activity against wild-type S. aureus, 21b also showed excellent pigment inhibition against four pigmented MRSA strains. In addition, H2O2 killing and human whole blood killing assays proved 21b could sensitize S. aureus to be killed under oxidative stress conditions. Notably, the murine study in vivo validated the efficacy of 21b against pigmented S. aureus Newman, vancomycin-intermediate S. aureus Mu50 and linezolid-resistant S. aureus NRS271.

Novel Terminal Bipheny-Based Diapophytoene Desaturases (CrtN) Inhibitors as Anti-MRSA/VISR/LRSA Agents with Reduced hERG Activity

CrtN has been identified as an attractive and druggable target for treating pigmented Staphylococcus aureus infections. More than 100 new compounds were synthesized, which target the overwhelming the defects of the CrtN inhibitor 1. Analogues 23a and 23b demonstrated a significant activity against pigmented S. aureus Newman and 13 MRSA strains (IC50 = 0.02-10.5 nM), along with lower hERG inhibition (IC50 > 30 μM, ～10-fold decrease in comparison with 1). Furthermore, 23a and 23b were confirmed to reduce the staphylococcal load in the kidney and heart in a mouse model with normal treatment deeper than pretreatment ones, comparable even with vancomycin and linezolid. Remarkably, 23a could strongly block the pigment biosynthesis of these nine multidrug-resistant MRSA strains, including excellent activity against LRSA strains and VISA strains in vivo, and all of which demonstrated that 23a has a huge potential against intractable MRSA, VISA, and LRSA issues as a therapeutic drug.

Novel Staphyloxanthin Inhibitors with Improved Potency against Multidrug Resistant Staphylococcus aureus

Diapophytoene desaturase (CrtN) is a potential novel target for intervening in the biosynthesis of the virulence factor staphyloxanthin. In this study, 38 1,4-benzodioxan-derived CrtN inhibitors were designed and synthesized to overwhelm the defects of leading compound 4a. Derivative 47 displayed superior pigment inhibitory activity, better hERG inhibitory properties and water solubility, and significantly sensitized MRSA strains to immune clearance in vitro. Notably, 47 displayed excellent efficacy against pigmented S. aureus Newman, Mu50 (vancomycin-intermediate MRSA, VISA), and NRS271 (linezolid-resistant MRSA, LRSA) comparable to that of linezolid and vancomycin in vivo.

trans-Cyclooctenes as Halolactonization Catalysts

The strained olefins in trans-cyclooctenes serve as efficient catalysts for halolactonizations, including bromolactonizations and iodolactonizations. The trans-cyclooctene framework is essential for excellent catalytic performance, and the substituents also play important roles in determining efficiency. These results are the first demonstration of catalysis by a trans-cyclooctene.

Novel Inhibitors of Staphyloxanthin Virulence Factor in Comparison with Linezolid and Vancomycin versus Methicillin-Resistant, Linezolid-Resistant, and Vancomycin-Intermediate Staphylococcus aureus Infections in Vivo

Our previous work (Wang et al. J. Med. Chem. 2016, 59, 4831-4848) revealed that effective benzocycloalkane-derived staphyloxanthin inhibitors against methicillin-resistant Staphylococcus aureus (S. aureus) infections were accompanied by poor water solubility and high hERG inhibition and dosages (preadministration). In this study, 92 chroman and coumaran derivatives as novel inhibitors have been addressed for overcoming deficiencies above. Derivatives 69 and 105 displayed excellent pigment inhibitory activities and low hERG inhibition, along with improvement of solubility by salt type selection. The broad and significantly potent antibacterial spectra of 69 and 105 were displayed first with normal administration in the livers and hearts in mice against pigmented S. aureus Newman, Mu50 (vancomycin-intermediate S. aureus), and NRS271 (linezolid-resistant S. aureus), compared with linezolid and vancomycin. In summary, both 69 and 105 have the potential to be developed as good antibacterial candidates targeting virulence factors.

Discovery of Benzocycloalkane Derivatives Efficiently Blocking Bacterial Virulence for the Treatment of Methicillin-Resistant S. aureus (MRSA) Infections by Targeting Diapophytoene Desaturase (CrtN)

Antivirulence strategies are now attracting interest for the inherent mechanism of action advantages. In our previous work, diapophytoene desaturase (CrtN) was identified to be an attractive and drugable target for fighting pigmented S. aureus infections. In this research, we developed a series of effective benzocycloalkane-derived CrtN inhibitors with submicromolar IC50. Analogue 8 blocked the pigment biosynthesis of three MRSA strains with a nanomolar IC50 value. Corresponding to its mode of action, 8 did not function as a bactericidal agent. 8 could sensitize S. aureus to immune clearance. In vivo, 8 was proven to be efficacious in an S. aureus Newman sepsis model and abscess formation model. For two typical MRSAs, USA400 MW2 and Mu50, 8 significantly decreased the staphylococcal loads in the liver and kidneys. Moreover, 8 showed minimal antifungal activity compared to that of NTF. In summary, 8 has the potential to be developed as a therapeutic drug, especially against intractable MRSA issues.

Chiral Br?nsted Acid Catalyzed Enantioselective Phosphonylation of Allylamine via Oxidative Dehydrogenation Coupling

A new strategy for the synthesis of chiral α-amino phosphonates by enantioselective C-H phosphonylation of allylamine with phosphite in the presence of a chiral Br?nsted acid catalyst has been developed. This protocol successfully integrates direct C-H oxidation with asymmetric phosphonylation and exhibits high enantioselectivity.