15677-00-6Relevant articles and documents
Highly Enantioselective Iridium-Catalyzed Hydrogenation of Conjugated Trisubstituted Enones
Peters, Bram B. C.,Jongcharoenkamol, Jira,Krajangsri, Suppachai,Andersson, Pher G.
supporting information, p. 242 - 246 (2021/01/13)
Asymmetric hydrogenation of conjugated enones is one of the most efficient and straightforward methods to prepare optically active ketones. In this study, chiral bidentate Ir-N,P complexes were utilized to access these scaffolds for ketones bearing the stereogenic center at both the α- and β-positions. Excellent enantiomeric excesses, of up to 99%, were obtained, accompanied with good to high isolated yields. Challenging dialkyl substituted substrates, which are difficult to hydrogenate with satisfactory chiral induction, were hydrogenated in a highly enantioselective fashion.
Derivatives of Natural Product Agrimophol as Disruptors of Intrabacterial pH Homeostasis in Mycobacterium tuberculosis
Wu, Jie,Mu, Ran,Sun, Mingna,Zhao, Nan,Pan, Miaomiao,Li, Hongshuang,Dong, Yi,Sun, Zhaogang,Bai, Jie,Hu, Minwan,Nathan, Carl F.,Javid, Babak,Liu, Gang
, p. 1087 - 1104 (2019/05/22)
This article reports the rational medicinal chemistry of a natural product, agrimophol (1), as a new disruptor of intrabacterial pH (pHIB) homeostasis in Mycobacterium tuberculosis (Mtb). Through the systematic investigation of the structure-activity relationship of 1, scaffold-hopping of the diphenylmethane scaffold, pharmacophore displacement strategies, and studies of the structure-metabolism relationship, a new derivative 5a was achieved. Compound 5a showed 100-fold increased potency in the ability to reduce pHIB to pH 6.0 and similarly improved mycobactericidal activity compared with 1 against both Mycobacterium bovis-BCG and Mtb. Compound 5a possessed improved metabolic stability in human liver microsomes and hepatocytes, lower cytotoxicity, higher selectivity index, and similar pKa value to natural 1. This study introduces a novel scaffold to an old drug, resulting in improved mycobactericidal activity through decreasing pHIB, and may contribute to the critical search for new agents to overcome drug resistance and persistence in the treatment of tuberculosis.
Iron-catalyzed asymmetric epoxidation of β,β-disubstituted enones
Nishikawa, Yasuhiro,Yamamoto, Hisashi
supporting information; experimental part, p. 8432 - 8435 (2011/07/29)
The combination of Fe(OTf)2 and novel phenanthroline ligands enables the catalytic asymmetric epoxidation of acyclic β,β- disubstituted enones, which have been a heretofore inaccessible substrate class. The reaction provides highly enantioenriched α,β-epoxyketones (up to 92% ee) that can be further converted to functionalized β-ketoaldehydes with an all-carbon quaternary center.
Synthesis and biological activity of permethrinic acid analogs containing various substituents in position 2 of the cyclopropane ring
Mirzabekova,Kuz'mina,Lukashov,Sokolova,Golosov,Kazakov,Perlova,Potapova,Kheinman,Ivanova
experimental part, p. 1139 - 1149 (2009/09/25)
A number of permethrinic acid ethyl ester derivatives having various substituents [Et, Pr, Ph, Ph(CH2) n (n = 1, 2), etc.] in position 2 of the cyclopropane ring were synthesized, and their insecticidal acivity against typhoid flies, rice weevils, and bean aphides, as well as juvenoid activity on flour beetle chrysalises, was studied. The newly synthesized compounds turned out to exhibit weak insecticidal activity against standard insects but pronounced juvenile hormone activity, which differentiates them from permethrinic acid esters.
Discovery of a series of pyrrolidine-based endothelin receptor antagonists with enhanced ET(A) receptor selectivity
Boyd, Steven A.,Mantei, Robert A.,Tasker, Andrew S.,Liu, Gang,Sorensen, Bryan K.,Henry Jr., Kenneth J.,Von Geldern, Thomas W.,Winn, Martin,Wu-Wong, Jinshyun R.,Chiou, William J.,Dixon, Douglas B.,Hutchins, Charles W.,Marsh, Kennan C.,Nguyen, Bach,Opgenorth, Terry J.
, p. 991 - 1002 (2007/10/03)
Endothelins, ET-1, ET-2, and ET-3 are potent vasoconstricting and mitogenic 21-amino acid bicyclic peptides, which exert their effects upon binding to the ET(A) and ET(B) receptors. The ET(A) receptor mediates vasoconstriction and smooth muscle cell proliferation, and the ET(B) receptor mediates different effects in different tissues, including nitric oxide release from endothelial cells, and vasoconstriction in certain vascular cell types. Selective antagonists of endothelin receptor subtypes may prove useful in determining the role of endothelin in various tissue types and disease states, and hence as therapeutic agents for such diseases. The pyrrolidine carboxylic acid A-127722 has been disclosed as a potent and ET(A)-selective antagonist, and is currently undergoing clinical trials. In our efforts to find antagonists with altered selectivity (ET(A)-selective, ET(B)-selective, or nonselective), we investigated the SAR of the 2-substituent on the pyrrolidine. Compounds with alkyl groups at the 2-position possessed ET(A) selectivity improved over A-127722 (1400-fold selective), with the best of these compounds showing nearly 19,000-fold selectivity. Copyright (C) 1999 Elsevier Science Ltd.
THE APPLICATION OF HIGH PRESSURE TO SOME DIFFICULT WITTIG REACTIONS
Isaacs, Neil S.,El-Din, Ghazi Najim
, p. 2191 - 2192 (2007/10/02)
Wittig reactions, previously shown to be favourably accelerated under pressure have been carried out between the stabilized ylides carboethoxymethylenetriphenylphosphorane and carboethoxyethylidinetriphenylphosphorane with a variety of ketones at 9-10 kbar pressure.Succesful formation of tri- and tetra-substituted ethylenes are reported.
