- A modified synthesis of O-hydroxyaryl aldehydes
-
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).
- Wang,You,Meng,Mintz,Bu
-
-
Read Online
- 2,2'-Bifurylidene-5,5'-diones, Coumarins, 3a,7a-Dihydro-1H-inden-1-ones, and 5H-Furopyran-5-ones from Propyne and Carbon Monoxide
-
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.
- Rautenstrauch, Valentin,Megard, Patrick,Gamper, Betty,Bourdin, Bernadette,Walther, Eric,Bernardinelli, Gerald
-
-
Read Online
- 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
-
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.
- Mazzei, Luca,Contaldo, Umberto,Musiani, Francesco,Cianci, Michele,Bagnolini, Greta,Roberti, Marinella,Ciurli, Stefano
-
supporting information
p. 6029 - 6035
(2021/02/09)
-
- SUBSTITUTED 4-[5-(BENZOFURAN-2-YL)-1,2,4-OXADIAZOL-3-YL]BENZOIC ACID COMPOUNDS FOR USE IN THERAPY FOR NEUROPATHIC PAIN
-
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))
- -
-
Page/Page column 36-37
(2020/12/11)
-
- Enantioselective Phenolic α-Oxidation Using H2O2 via an Unusual Double Dearomatization Mechanism
-
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.
- McLaughlin, Michael F.,Massolo, Elisabetta,Liu, Shubin,Johnson, Jeffrey S.
-
-
- Enantioselective phenolic a-oxidation using H2O2 via an unusual double dearomatization mechanism
-
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.
- McLaughlin, Michael F.,Massolo, Elisabetta,Liu, Shubin,Johnson, Jeffrey S.
-
p. 2645 - 2651
(2019/07/04)
-
- Directed Remote Lateral Metalation: Highly Substituted 2-Naphthols and BINOLs by In Situ Generation of a Directing Group
-
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.
- Patel, Jignesh J.,Laars, Marju,Gan, Wei,Board, Johnathan,Kitching, Matthew O.,Snieckus, Victor
-
supporting information
p. 9425 - 9429
(2018/07/29)
-
- CRYSTALLINE FORMS OF 4-(5-(4,7-DIMETHYLBENZOFURAN-2-YL)-1,2,4-OXADIAZOL-3-YL)BENZOIC ACID AND PROCESSES FOR THEIR PREPARATION
-
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.
- -
-
Page/Page column 22
(2018/04/11)
-
- Synthesis of methylated quercetin analogues for enhancement of radical-scavenging activity
-
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.
- 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)
-
- Inhibitors of viral replication, their process of preparation and their therapeutical uses
-
The present invention relates to compounds, their use in the treatment or the prevention of viral disorders, including HIV.
- -
-
Paragraph 1197; 1198; 1199
(2016/06/28)
-
- BICYCLOHETEROARYL-HETEROARYL-BENZOIC ACID COMPOUNDS AS RETINOIC ACID RECEPTOR BETA (RARβ) AGONISTS
-
The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain bicycloheteroaryl-heteroaryl-benzoic acid compounds of the following formula (for convenience, collectively referred to herein as "BHBA compou
- -
-
Page/Page column 64; 65
(2016/07/05)
-
- INK COMPOSITION, INKJET RECORDING METHOD, PRINTED MATTER, AND HIGH-MOLECULAR-WEIGHT POLYMERIZATION INITIATOR
-
An ink composition contains (component A) a high-molecular-weight polymerization initiator having a weight-average molecular weight of equal to or greater than 1,000, (component B) a polymerizable compound, and (component C) a colorant, in which the component A has an acylphosphine oxide structure, and the acylphosphine oxide structure is linked to a main chain or a core of the component A on the side of an acyl group thereof.
- -
-
-
- A convenient synthesis of tri- and tetramethylbenzaldehydes from readily available phenols
-
This letter describes a convenient synthesis of the six isomeric tri- and tetramethylbenzaldehydes, which are not readily available from major chemical suppliers. Formylation of readily available phenols via electrophilic aromatic substitution provides compounds containing the correct aromatic substitution pattern. ?Suzuki cross-coupling of the corresponding trifluoromethanesulfonates with methylboronic acid then provides the benzaldehydes as single isomers. Georg Thieme Verlag Stuttgart. New York.
- Dhankher, Persis,Sheppard, Tom D.
-
supporting information
p. 381 - 384
(2014/03/21)
-
- Photocycloaddition of arenes and allenes
-
In this work, we report on a new intramolecular para cycloaddition of arenes with allenes, yielding attractive rigid scaffolds bearing several reactive functionalities to build in further diversity. Bicyclo[2.2.2]octadiene- type products and benzoxepine acetals are formed in this reaction, in ratios and yields depending on the substitution pattern on the aromatic ring, the nature of the chromophore, and the tether. This unprecedented reaction has remarkable features that distinguish it from many other photochemical transformations: it is particularly robust with respect to substituents, it can be scaled up without a notable loss of efficiency, and it can lead to structures with a high degree of complexity in low to good yields. All photochemical precursors could be synthesized readily in three steps. We confirmed the compatibility of the nitrogen atom in the photocycloaddition step, which gives access to a bicyclo[2.2.2]octadiene scaffold with two points that allow further diversification. This reaction was scaled up to multigram quantities without erosion of the typically high yields in photocycloadducts. Sequential deprotection of the N- or C-terminus of bicyclic amino acids gave access to two conformationally constrained unnatural amino acids with different dispositions of the two anchor points.
- Streit, Ursula,Birbaum, Frederic,Quattropani, Anna,Bochet, Christian G.
-
p. 6890 - 6910
(2013/08/23)
-
- Asymmetric induction via short-lived chiral enolates with a chiral C-O axis
-
A novel method has been developed for the asymmetric cyclization of alkyl aryl ethers. The reactions were assumed to proceed via short-lived chiral enolate intermediates with a chiral C-O axis to give cyclic ethers with tetrasubstituted carbon in up to 99% ee. The half-life of racemization of the chiral enolate intermediate was roughly estimated to be ~1 s at -78 C.
- Yoshimura, Tomoyuki,Tomohara, Keisuke,Kawabata, Takeo
-
supporting information
p. 7102 - 7105
(2013/06/27)
-
- INHIBITORS OF VIRAL REPLICATION, THEIR PROCESS OF PREPARATION AND THEIR THERAPEUTICAL USES
-
The present invention relates to compounds, their use in the treatment or the prevention of viral disorders, including HIV.
- -
-
Page/Page column 137-138
(2012/11/06)
-
- An expedient synthesis of ellipticine via Suzuki-Miyaura coupling
-
A simple and efficient total synthesis of ellipticine was developed via the Suzuki-Miyaura coupling of sterically sensitive 2-hydroxybenzeneboronic acid with a multifunctional aryl halide using Pd(OAc)2 as a catalyst and Cu(OAc)2·H2O as an additive in DMSO/H2O as a key step followed by double N-arylation and cyclization.
- Konakahara, Takeo,Kiran,Okuno, Yuri,Ikeda, Reiko,Sakai, Norio
-
supporting information; experimental part
p. 2335 - 2338
(2010/06/13)
-
- The novel benzopyran class of selective cyclooxygenase-2 inhibitors. Part III: The three microdose candidates
-
In this manuscript, we report the discovery of the substituted 2-trifluoromethyl-2H-benzopyran-3-carboxylic acids as a novel series of potent and selective cyclooxygenase-2 (COX-2) inhibitors. We provide the structure-activity relationships, optimization of design, testing criteria, and human half-life data. The challenge of a surprisingly long half-life (t 1/2 = 360 h) of the first clinical candidate 1 and human t 1/2 had been difficult to predict based on allometric scaling for this class of highly ppb compounds. We used a microdose strategy which led to the discovery of clinical agents 18c-(S), 29b-(S), and 34b-(S) with human half-life of 57, 13, and 11 h.
- Wang, Jane L.,Aston, Karl,Limburg, David,Ludwig, Cindy,Hallinan, Ann E.,Koszyk, Francis,Hamper, Bruce,Brown, David,Graneto, Matthew,Talley, John,Maziasz, Timothy,Masferrer, Jaime,Carter, Jeffery
-
scheme or table
p. 7164 - 7168
(2011/01/03)
-
- Asymmetric syntheses of highly functionalized bicyclo [2.2.2] octene derivatives
-
Highly functionalized bicyclo[2.2.2]octene derivatives bearing two quaternary carbon centers were synthesized in an asymmetric fashion. The key transformations were the regioselective Diels-Alder reaction between 3,6-dimethyl-o-quinone monoacetal and 1,1-diethoxyethylene and the subsequent enzymatic resolution. The optically active bicyclo[2.2.2]octene derivatives obtained should serve as versatile chiral building blocks for highly functionalized natural products such as ryanodine. The Japan Institute of Heterocyclic Chemistry.
- Iwatsu, Masafumi,Urabe, Daisuke,Inoue, Masayuki
-
p. 491 - 504
(2013/08/23)
-
- CHEMICAL COMPOUNDS
-
This invention relates to non-steroidal compounds that are modulators of androgen receptor, and also to the methods for the making and use of such compounds.
- -
-
Page/Page column 28
(2008/12/04)
-
- Radical and migratory insertion reaction mechanisms in Schiff base zirconium alkyls
-
Four salicylaldimine derivatives H2L4-7 of 2,2′-diamino-6,6′-dimethylbiphenyl, where the CN bond is sterically protected by substituents on the phenol ring, form alkyls of zirconium, cis-α-[ZrL4-7(CH2Ph)2/
- Knight, Paul D.,Clarkson, Guy,Hammond, Max L.,Kimberley, Brian S.,Scott, Peter
-
p. 5125 - 5144
(2007/10/03)
-
- Non-metallocene compounds, method for the production thereof and use of the same for the polymerisation of olefins
-
The invention relates to a method for producing special transition metal compounds, to novel transition metal compounds and to the use of the same for the polymerisation of olefins.
- -
-
-
- BENZOPYRAN COMPOUNDS USEFUL FOR TREATING INFLAMMATORY CONDITIONS
-
The subject invention concerns methods and compounds that have utility in the treatment of a condition associated with cyclooxygenase-2 mediated disorders. Compounds of particular interest are benzopyrans and their analogs defined by formula (1). Wherein Z, X, R1, R2, R3, and R4 are as described in specification.
- -
-
-
- CHROMENE DERIVATIVES AS ANTI-INFLAMMATORY AGENTS
-
The subject invention concerns methods and compounds that have utility in the treatment of a condition associated with cyclooxygenase-2 mediated disorders. Compounds of particular interest are benzopyrans and their analogs defined by formula (I). Wherein Z, X, R1, R2, R3, and R4 are as described in the specification.
- -
-
-
- Photochemical synthesis, conformational analysis, and transformation of [60]fullerene-o-quinodimethane adducts bearing a hydroxy group
-
The photochemical reactions of [60]fullerene with various aromatic aldehydes or ketones 1a-n carrying an alkyl group at the ortho position were examined. Some of them afforded stable o-quinodimethane adducts 2 with a hydroxy group attached to the cyclohexene ring. The adducts 2 were found to adopt one or both of two conformers A and E, which possess pseudoaxial and pseudoequatorial hydroxy groups, respectively. The conformer ratios depended remarkably on the substituents attached to the aromatic nucleus and the cyclohexene ring. The dynamic behavior of 2 was also investigated by the VT-NMR technique.
- Nakamura, Yosuke,O-kawa, Kyoji,Minami, Satoshi,Ogawa, Toshio,Tobita, Seiji,Nishimura, Jun
-
p. 1247 - 1252
(2007/10/03)
-
- Electroorganic reactions. Part 55. Quinodimethane chemistry. Part 3. Transition metal complexes as inter- and intra-molecular redox catalysts for the electrosynthesis of poly(p-xylylene) (PPX) polymers and oligomers
-
The role of metal complexes as redox mediators in the electrosynthesis of poly(p-xylylenes) (PPXs) has been explored, with a view to designing metal-containing precursors that can act both as mediators and starting materials for metal-containing polymers. A number of transition metal complexes [Cr(III), Ni(II) and Co(II)] are efficient redox catalysts for production of quinodimethanes, and hence PPXs. Following encouraging results from experiments using mediators based on anthranilic acid and salicylaldehyde ligands a macrocyclic compound was designed, and successfully prepared by a convergent route that incorporated both a 1,4-bis(chloromethylarene) function as a precursor to a quinodimethane and a Ni(II) salen unit as an intramolecular redox catalyst. The macrocycle was successfully reduced cathodically to yield a PPX polymer with bound Ni(II). Evidence is presented for the operation of intramolecular redox catalysis (homomediation).
- Janssen,Utley,Carre?,Simon,Schirmer
-
p. 1573 - 1584
(2007/10/03)
-
- Studies on triepoxide analogs of triptolide
-
Several triepoxide analogs of triptolide were synthesized efficiently using in situ generated dioxiranes and basic hydrogen peroxide. Two of them were found to be cytotoxic.
- Yang, Dan,Wong, Man-Kin,Cheung, Kung-Kai,Chan,Xie, Yong
-
p. 6865 - 6868
(2007/10/03)
-
- Synthetic studies on maduropeptin chromophore 2. Synthesis of the madurosamine aryl amide and the C1'-C9' fragments
-
A retrosynthetic analysis (Scheme 1) of maduropeptin chromophore artifact 1 defined compounds 2 and 3 as required building blocks. The construction of 2 was achieved starting from the 2,5-dimethyl derived aromatic acid 8 and the D-serine derived δ-lactone
- Nicolaou,Koide, Kazunori,Xu, Jinyou,Izraelewicz, Mark H.
-
p. 3671 - 3674
(2007/10/03)
-
- Steric acceleration of intramolecular cycloaddition reactions
-
Use of conformational constraints, induced by different ortho-substituents in 1-allyloxy-2-(substituted)methylbenzenes, where the substituent is a 1,3-dipole such as the azide or 3-oxidopyridinium group, can be employed to accelerate the 1,3-dipolar cycloaddition reaction. In this manner cycloadditions that otherwise do not proceed can be forced to react.
- Orlek, Barry S.,Sammes, Peter G.,Weller, David J.
-
p. 8179 - 8194
(2007/10/02)
-
- Selective Reactions between Phenols and Formaldehyde. A Novel Route to Salicylaldehydes
-
Treatment of phenols (1) with 2 mol equiv. of paraformaldehyde in aprotic and poorly electron-donating solvents in the presence of selected metal halides coupled with suitable bases produces salicylaldehydes (3) in high yields.The route is highly selective for ortho-formylation and also specific towards monoformylation.The crucial role of added bases is emphasized.
- Casiraghi, Giovanni,Casnati, Giuseppe,Puglia, Giuseppe,Sartori, Giovanni,Terenghi, Giuliana
-
p. 1862 - 1865
(2007/10/02)
-