1666-04-2Relevant articles and documents
A modified synthesis of O-hydroxyaryl aldehydes
Wang,You,Meng,Mintz,Bu
, p. 1757 - 1760 (1994)
A modified method for the synthesis of o-hydroxyaryl aldehydes in moderate yields has been developed by treating aryloxymagnesium bromides with formaldehyde using triethylamine in place of hexamethylphosphoric triamide (HMPA).
2,2'-Bifurylidene-5,5'-diones, Coumarins, 3a,7a-Dihydro-1H-inden-1-ones, and 5H-Furopyran-5-ones from Propyne and Carbon Monoxide
Rautenstrauch, Valentin,Megard, Patrick,Gamper, Betty,Bourdin, Bernadette,Walther, Eric,Bernardinelli, Gerald
, p. 811 - 824 (1989)
The -catalyzed reaction between propyne and CO in acetone at 110 deg C and 170 bar was reinvestigated.There are five major products: (E)-3,4'-dimethyl-2,2'-bifurylidene-5,5'-dione (4), 3,5,8-trimethylcoumarin (8), 3a,7a-dihydro-2,4,7,7a-tetramethyl-1H-inden-1-one (9), 2,6-dimethyl-5H-furopyran-5-one (11), and 2,7-dimethyl-5H-furopyran-5-one (12); of these, only one, 4, had previously been recognized.In parallel experiments were obtained 2,6-dipentyl-5H-furopyran-5-one (13), 2,7-dipentyl-5H-furopyran-5-one (14), 3a,7a-dihydro-2,4,7,7a-tetrapentyl-1H-inden-1-one (15), and 3a,7a-dihydro-2,4,6,7a-tetrapentyl-1H-inden-1-one (16) from hept-1-yne, and two further types of products from two atypical 1-alkynes: 3,6,9-tri(tert-butyl)-1-oxaspironona-3,6,8-trien-2-one (20) from (tert-butyl)acetylene and the exo-dimer 21 of 2,5-bis(trimethylsilyl)cyclopenta-2,4-dien-1-one (22) from (trimethylsilyl)acetylene.Compounds 11, 12, and 20 were identified by X-ray analysis.
Inhibition of Urease, a Ni-Enzyme: The Reactivity of a Key Thiol With Mono- and Di-Substituted Catechols Elucidated by Kinetic, Structural, and Theoretical Studies
Mazzei, Luca,Contaldo, Umberto,Musiani, Francesco,Cianci, Michele,Bagnolini, Greta,Roberti, Marinella,Ciurli, Stefano
supporting information, p. 6029 - 6035 (2021/02/09)
The inhibition of urease from Sporosarcina pasteurii (SPU) and Canavalia ensiformis (jack bean, JBU) by a class of six aromatic poly-hydroxylated molecules, namely mono- and dimethyl-substituted catechols, was investigated on the basis of the inhibitory efficiency of the catechol scaffold. The aim was to probe the key step of a mechanism proposed for the inhibition of SPU by catechol, namely the sulfanyl radical attack on the aromatic ring, as well as to obtain critical information on the effect of substituents of the catechol aromatic ring on the inhibition efficacy of its derivatives. The crystal structures of all six SPU-inhibitors complexes, determined at high resolution, as well as kinetic data obtained on JBU and theoretical studies of the reaction mechanism using quantum mechanical calculations, revealed the occurrence of an irreversible inactivation of urease by means of a radical-based autocatalytic multistep mechanism, and indicate that, among all tested catechols, the mono-substituted 3-methyl-catechol is the most efficient inhibitor for urease.
SUBSTITUTED 4-[5-(BENZOFURAN-2-YL)-1,2,4-OXADIAZOL-3-YL]BENZOIC ACID COMPOUNDS FOR USE IN THERAPY FOR NEUROPATHIC PAIN
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Page/Page column 36-37, (2020/12/11)
The present invention pertains generally to the field of therapy. More specifically, the present invention pertains to certain substituted 4-[5-(benzofuran-2-yl)-1,2,4-oxadiazol-3-yl]benzoic acid compounds (collectively referred to herein as BOBA compounds), and pharmaceutical compositions comprising those compounds, for use in a method of treatment or prevention of neuropathic pain. (Formula (A))
Enantioselective Phenolic α-Oxidation Using H2O2 via an Unusual Double Dearomatization Mechanism
McLaughlin, Michael F.,Massolo, Elisabetta,Liu, Shubin,Johnson, Jeffrey S.
, (2019/02/14)
Feedstock aromatic compounds are compelling low-cost starting points from which molecular complexity can be generated rapidly via oxidative dearomatization. Oxidative dearomatizations commonly rely heavily on hypervalent iodine or heavy metals to provide the requisite thermodynamic driving force for overcoming aromatic stabilization energy. This article describes oxidative dearomatizations of 2-(hydroxymethyl)phenols via their derived bis(dichloroacetates) using hydrogen peroxide as a mild oxidant that intercepts a transient quinone methide. A stereochemical study revealed that the reaction proceeds by a new mechanism relative to other phenol dearomatizations and is complementary to extant methods that rely on hypervalent iodine. Using a new chiral phase-transfer catalyst, the first asymmetric syntheses of 1-oxaspiro[2.5]octa-5,7-dien-4-ones were reported. The synthetic utility of the derived 1-oxaspiro[2.5]octadienones products is demonstrated in a downstream complexity-generating transformation.
Enantioselective phenolic a-oxidation using H2O2 via an unusual double dearomatization mechanism
McLaughlin, Michael F.,Massolo, Elisabetta,Liu, Shubin,Johnson, Jeffrey S.
, p. 2645 - 2651 (2019/07/04)
Feedstock aromatic compounds are compelling low-cost starting points from which molecular complexity can be generated rapidly via oxidative dearomatization. Oxidative dearomatizations commonly rely heavily on hypervalent iodine or heavy metals to provide the requisite thermodynamic driving force for overcoming aromatic stabilization energy. This article describes oxidative dearomatizations of 2- (hydroxymethyl)phenols via their derived bis(dichloroacetates) using hydrogen peroxide as a mild oxidant that intercepts a transient quinone methide. A stereochemical study revealed that the reaction proceeds by a new mechanism relative to other phenol dearomatizations and is complementary to extant methods that rely on hypervalent iodine. Using a new chiral phasetransfer catalyst, the first asymmetric syntheses of 1-oxaspiro[2.5]octa-5,7-dien-4-ones were reported. The synthetic utility of the derived 1-oxaspiro[2.5]octadienones products is demonstrated in a downstream complexity-generating transformation.
Directed Remote Lateral Metalation: Highly Substituted 2-Naphthols and BINOLs by In Situ Generation of a Directing Group
Patel, Jignesh J.,Laars, Marju,Gan, Wei,Board, Johnathan,Kitching, Matthew O.,Snieckus, Victor
supporting information, p. 9425 - 9429 (2018/07/29)
A general synthesis of highly substituted 2-naphthols based on a new carbanionic reaction sequence is demonstrated. The reaction exploits the dual nature of lithium bases consisting of consecutive ring opening of readily available coumarins with either LiNEt2 or LiNiPr2 into Z-cinnamamides, thus generating a directing group in situ and allowing, by conformational freedom, a lateral directed remote metalation for ring closure to give the aryl 2-naphthols in good to excellent yields. These transformations can be combined to provide a more efficient one-pot process. Mechanistic insight into the remote lateral metalation step, demonstrating the requirement of Z-cinnamamide, is described. Application of this methodology to the synthesis of highly substituted 3,3′-diaryl BINOL ligands is also reported.
CRYSTALLINE FORMS OF 4-(5-(4,7-DIMETHYLBENZOFURAN-2-YL)-1,2,4-OXADIAZOL-3-YL)BENZOIC ACID AND PROCESSES FOR THEIR PREPARATION
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Page/Page column 22, (2018/04/11)
The present invention pertains generally to the field of therapeutic compounds, and more specifically to crystalline forms of 4-(5-(4,7-dimethylbenzofuran-2-yl)-1,2,4-oxadiazol-3-yl)benzoic acid (referred to herein as "BHBA-001"), which, inter alia, is a (selective) retinoic acid receptor beta (RARβ) (e.g., RARβ2) agonist. The present invention also pertains to pharmaceutical compositions comprising such crystalline forms, and the use of such crystalline forms and compositions, both in vitro and in vivo, to (selectively) activate RARβ (e.g., RARβ2), to cause or promote neurite development, neurite outgrowth, and/or neurite regeneration, and in the treatment of diseases and conditions that are mediated by RARβ (e.g., RARβ2), that are ameliorated by the activation of RARβ (e.g., RARβ2), etc., including, e.g., neurological injuries such as spinal cord injuries.
Synthesis of methylated quercetin analogues for enhancement of radical-scavenging activity
Imai, Kohei,Nakanishi, Ikuo,Ohkubo, Kei,Ohba, Yusuke,Arai, Takuya,Mizuno, Mirei,Fukuzumi, Shunichi,Matsumoto, Ken-ichiro,Fukuhara, Kiyoshi
, p. 17968 - 17979 (2017/03/31)
Three quercetin derivatives with enhanced radical-scavenging activity were designed and synthesised. Because the radical-scavenging reaction of quercetin is known to proceed via an electron transfer from quercetin to radicals, producing the corresponding quercetin radical cation intermediate, the introduction of electron-donating groups into the quercetin molecule is expected to enhance its radical-scavenging activity. Thus, methyl groups were introduced into the catechol moiety in the quercetin molecule at either the 2′- or 5′-position, or both. All three quercetin analogues were found to exhibit higher radical-scavenging activity than the parent quercetin. The activity of 5′-methylquercetin is the highest among the three analogues. The optimised structure of 5′-methylquercetin calculated by density functional theory demonstrated a coplanar structure between the 4H-curomen (AC rings) and catechol (B ring) moieties, while dimethylquercetin and 2′-methylquercetin have a twisted structure between the AC and B rings. These results demonstrate that the highest radical-scavenging activity of 5′-methylquercetin is due to the stabilisation of the radical cation intermediate by the electron-donating effect of the methyl group as well as by the planar structure of the molecule.
Inhibitors of viral replication, their process of preparation and their therapeutical uses
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Paragraph 1197; 1198; 1199, (2016/06/28)
The present invention relates to compounds, their use in the treatment or the prevention of viral disorders, including HIV.
