- Dearomative enantio- and diastereoselective difluorination of resorcinol derivatives
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We herein report enantio- and diastereoselective fluorination of naphthoresorcinol and resorcinol derivatives for the first time using a dicarboxylate phase-transfer catalyst. Stereoselective oxidative transformation of resorcinol derivatives is considered to be difficult because of their high reactivity, multiple reaction sites, and multiple hydrogen bond interactions due to the presence of the two hydroxy groups. Even though resorcinol and its oxidized frameworks are widely found in bioactive natural compounds, dearomative asymmetric fluorination of resorcinol derivatives remains unexplored. We found that our chiral dicarboxylate phase-transfer catalyst could serve as an effective catalyst for the purpose. Interestingly, naphthoresorcinols and resorcinols were converted to difluorination products preferentially rather than monofluorinated products. It is noteworthy that asymmetric desymmetrization of symmetrically substituted resorcinols occurred with up to 95% ee and the reaction was tolerant of various functional groups.
- Egami, Hiromichi,Hamashima, Yoshitaka,Otsubo, Minami,Sakimoto, Kousuke
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supporting information
(2021/08/18)
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- Yicathins B and C and Analogues: Total Synthesis, Lipophilicity and Biological Activities
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Natural products have always been an important source of new hits and leads in drug discovery, with the marine environment being regarded as a significant source of novel and exquisite bioactive compounds. Yicathins B and C are two marine-derived xanthones that have shown antibacterial and antifungal activity. Herein, the total synthesis of these yicathins and six novel analogues is reported for the first time. As marine natural products tend to have very lipophilic scaffolds, the lipophilicity of yicathins and their analogues was evaluated in the classical octanol/water system and a biomimetic model-based system. As the xanthonic nucleus is a “privileged structure”, other biological activities were evaluated, namely antitumor and anti-inflammatory activities. An interesting anti-inflammatory activity was identified for yicathin analogues that paves the way for the design of dual activity (anti-infective and anti-inflammatory) marine-inspired xanthone derivatives.
- Afonso, Carlos M. M.,Azevedo, Carlos M. G.,Bousbaa, Hassan,Ferreira, Helena,Henriques, Ana,Loureiro, Daniela R. P.,Magalh?es, álvaro F.,Neves, Nuno,Pinto, Joana,Pinto, Madalena M. M.,Reis, Salette,Soares, José X.,Vieira, Sara
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supporting information
(2020/04/17)
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- PROCESS AND INTERMEDIATES FOR THE SYNTHESIS OF VOXELOTOR
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The invention relates to a process for the preparation of Voxelotor, or a salt or solvate thereof, according to the following scheme (Formula 1).
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Page/Page column 20
(2020/07/14)
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- Competitive Binding Assay with an Umbelliferone-Based Fluorescent Rexinoid for Retinoid X Receptor Ligand Screening
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Ligands for retinoid X receptors (RXRs), "rexinoids", are attracting interest as candidates for therapy of type 2 diabetes and Alzheimer's and Parkinson's diseases. However, current screening methods for rexinoids are slow and require special apparatus or facilities. Here, we created 7-hydroxy-2-oxo-6-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-2H-chromene-3-carboxylic acid (10, CU-6PMN) as a new fluorescent RXR agonist and developed a screening system of rexinoids using 10. Compound 10 was designed based on the fact that umbelliferone emits strong fluorescence in a hydrophilic environment, but the fluorescence intensity decreases in hydrophobic environments such as the interior of proteins. The developed assay using 10 enabled screening of rexinoids to be performed easily within a few hours by monitoring changes of fluorescence intensity with widely available fluorescence microplate readers, without the need for processes such as filtration.
- Yamada, Shoya,Kawasaki, Mayu,Fujihara, Michiko,Watanabe, Masaki,Takamura, Yuta,Takioku, Maho,Nishioka, Hiromi,Takeuchi, Yasuo,Makishima, Makoto,Motoyama, Tomoharu,Ito, Sohei,Tokiwa, Hiroaki,Nakano, Shogo,Kakuta, Hiroki
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p. 8809 - 8818
(2019/10/11)
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- Synthesis of bavachromanol from resorcinol via a tandem cationic cascade/EAS sequence
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The natural chalcone bavachromanol has been prepared through a tandem reaction sequence that joins cationic cyclization of an epoxide to an adjacent MOM-acetal with electrophilic aromatic substitution by a presumed methoxymethylene cation. Only a single regioisomer of the tandem product was observed, with substitution taking place exclusively ortho to the position of the original acetal. This regiocontrol provided a key intermediate from a symmetrical precursor, and allowed preparation of the meroterpenoid through a short reaction sequence.
- Shah, Parin A.,Wiemer, David F.
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supporting information
p. 1363 - 1365
(2018/03/07)
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- A pH-responsive molecular capsule with an acridine shell: Catch and release of large hydrophobic compounds
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Unlike common polyaromatic hydrocarbons, acridine is a characteristic compound bearing both π-stackable large surfaces and a protonable nitrogen atom. Here we report the first synthesis of a supramolecular capsule with multiple acridine panels. In water, the assembly and disassembly of the capsule reversibly occur under neutral and acidic conditions, respectively (≥10 cycles). Notably, the pH-responsive capsule encapsulates a variety of large hydrophobic compounds (up to 1.6 nm in diameter) such as coumarins, metallophthalocyanines and subphthalocyanine in neutral water and subsequently releases them by simple addition of acid.
- Kishimoto, Mai,Kondo, Kei,Akita, Munetaka,Yoshizawa, Michito
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supporting information
p. 1425 - 1428
(2017/02/05)
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- HYDANTOIN MODULATORS OF KV3 CHANNELS
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The invention provides compounds of formula (I): Said compounds being inhibitors of Kv3 channels and of use in the prophylaxis or treatment of related disorders.
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Page/Page column 55
(2017/07/06)
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- Enzyme-Catalyzed Intramolecular Enantioselective Hydroalkoxylation
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Hydroalkoxylation is a powerful and efficient method of forming C-O bonds and cyclic ethers in synthetic chemistry. In studying the biosynthesis of the fungal natural product herqueinone, we identified an enzyme that can perform an intramolecular enantios
- Gao, Shu-Shan,Garcia-Borràs, Marc,Barber, Joyann S.,Hai, Yang,Duan, Abing,Garg, Neil K.,Houk,Tang, Yi
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supporting information
p. 3639 - 3642
(2017/03/20)
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- Bismuth trichloride–mediated cleavage of phenolic methoxymethyl ethers
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A simple and efficient method for removal of phenolic methoxymethyl ethers in the presence of 30?mol% of bismuth trichloride in acetonitrile/water is described. Notable features of the cleavage protocol entail use of an ecofriendly bismuth reagent, ease of handling, low cost, operational simplicity, and good functional group compatibility. A number of structurally varied phenolic methoxymethyl ethers were cleaved in good to excellent yields.
- Obaro-Best, Oghale,Reed, Jack,Norfadilah, Alya A. F. B.,Monahan, Ryan,Sunasee, Rajesh
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supporting information
p. 586 - 593
(2016/06/08)
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- CRYSTALLINE 2-HYDROXY-6-((2-(1-ISOPROPYL-1H-PYRAZOL-5-YL)PYRIDIN-3-YL)METHOXY)BENZALDEHYDE ANSOLVATE SALTS
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Disclosed are crystalline ansolvate salts of 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde (or Compound 1), such as the hydrochloride Form I.
- -
-
Paragraph 0062; 0065
(2015/03/16)
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- Crystalline Polymorphs of the Free Base of 2-Hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde
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Disclosed are crystalline free base ansolvate forms of 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde (or Compound 1), such as the free base Form I, Form II and Material N. Also disclosed are crystalline free base solvates of 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde (or Compound 1).
- -
-
Paragraph 0109-0112
(2015/09/22)
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- Synthesis of isobavachalcone and some organometallic derivatives
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Isobavachalcone [2′,4,4′-trihydroxy-3′-(3″-methyl- 2″-butenyl)chalcone, 1] is a prenylated chalcone that has broad biological activity, in particular against neuroblastomas, the most common cancer in infancy. It is currently commercially available at a cost of 190/mg by extraction from Psoralea corylifolia and a number of other African and Asian plants. Several synthetic routes have been explored, and the most efficient procedure involves the palladium-catalysed Stille coupling of 3-iodo-2,4-bis(methoxymethoxy)acetophenone (25) with prenyltributyltin, Claisen-Schmidt condensation with 4-(methoxymethoxy)benzaldehyde to form the triply MOM-protected prenylchalcone 27 and finally deprotection with 2 M HCl in methanol to form isobavachalcone in an overall yield of 15 % over five steps. The X-ray crystal structures of 2,4-dihydroxy-3-iodoacetophenone (21) and of several prenylated chalcones are reported, including the elucidation of their hydrogen-bonding networks in the solid state. The synthetic route has been extended to include organometallic derivatives in which the 4-(methoxymethoxy) benzaldehyde used in the Claisen-Schmidt condensation has been replaced by formylferrocene, formylruthenocene or (η5-formylcyclopentadienyl) (η4-tetraphenylcyclobutadiene)cobalt to form the corresponding analogues of isobavachalcone containing organometallic sandwich moieties.
- Grealis, John P.,Mueller-Bunz, Helge,Ortin, Yannick,Casey, Michael,McGlinchey, Michael J.
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p. 332 - 347
(2013/03/13)
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- Enantioselective synthesis of multisubstituted biaryl skeleton by chiral phosphoric acid catalyzed desymmetrization/kinetic resolution sequence
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Described herein is the enantioselective synthesis of multisubstituted biaryl derivatives by chiral phosphoric acid catalyzed asymmetric bromination. Two asymmetric reactions (desymmetrization and kinetic resolution) proceeded successively to afford chiral biaryls in excellent enantioselectivities (up to 99% ee). Both experimental and computational studies suggested that this excellent selectivity could be achieved via a highly organized hydrogen bond network among a substrate, a catalyst (chiral phosphoric acid), and a brominating reagent (N-bromophthalimide).
- Mori, Keiji,Ichikawa, Yuki,Kobayashi, Manato,Shibata, Yukihiro,Yamanaka, Masahiro,Akiyama, Takahiko
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supporting information
p. 3964 - 3970
(2013/04/24)
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- HYDANTOIN DERIVATIVES USEFUL AS KV3 INHIBITORS
-
The invention provides compounds of formula (I): Said compounds being inhibitors of Kv3 channels and of use in the prophylaxis or treatment of related disorders.
- -
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Paragraph 0555-0557
(2013/10/22)
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- The chirality conversion reagent for amino acids based on salicyl aldehyde
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2-Hydroxy-6-(1-(3-phenylurylphenyl)ethoxy)-benzaldehyde (2) has been synthesized in racemic form from 1,3-Dihydroxybenzene via formylation and reaction with 3-phenyluryl-methylbenzylbromide. The optically pure form of 2 was separated by normal silica colu
- Yoon, Hoe-Jin,Jung, Hein,Ahn, Yun Soo,Nandhakumar, Raju,Kim, Jun Soo,Kim, Kwan Mook
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experimental part
p. 1715 - 1718
(2012/07/30)
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- Total synthesis of (±)-sorocenol B employing nanoparticle catalysis
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The total synthesis of (±)-sorocenol B has been accomplished featuring key steps including silver nanoparticle (AgNP)-catalyzed Diels-Alder cycloaddition and late-stage Pd(II)-catalyzed oxidative cyclization. The synthetic natural product exhibited low mi
- Cong, Huan,Porco, John A.
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supporting information; scheme or table
p. 2516 - 2519
(2012/09/08)
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- HYDANTOIN DERIVATIVES USEFUL AS KV3 INHIBITORS
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The invention provides compounds of formula (I): Said compounds being inhibitors of Kv3 channels and of use in the prophylaxis or treatment of related disorders.
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-
Page/Page column 72
(2012/06/30)
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- IMIDAZOLIDINEDIONE DERIVATIVES
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The invention provides a compound of formula (Ia), and pharmaceutically acceptable salts thereof. The invention also provides use of the compounds or salts as modulators of Kv3.1 and/or Kv3.2, and in the treatment of diseases or disorders where a modulator of Kv3.1 and/or Kv3.2 is required, such as depression and mood disorders, hearing disorders, schizopherenea, substance abuse disorders, sleep disorders or epilepsy.
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Page/Page column 143-144
(2011/06/26)
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- Total synthesis of the pyranocoumaronochromone lupinalbin H
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The pyranocoumaronochromone lupinalbin H was synthesized in three major steps, which involved preparation of 2′-hydroxygenistein by the Suzuki-Miyaura reaction, followed by oxidative cyclodehydrogenation into lupinalbin A. The final step was the regiospec
- Selepe, Mamoalosi A.,Drewes, Siegfried E.,Van Heerden, Fanie R.
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experimental part
p. 8654 - 8658
(2011/12/01)
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- NOVOBIOCIN ANALOGUES AND TREATMENT OF POLYCYSTIC KIDNEY DISEASE
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Novobiocin analogues are useful in methods of treating, inhibiting, and/or preventing cyst formation in autosomal dominant polycystic kidney disease (ADPKD) in a subject. The disclosure provides methods of treating ADPKD comprising administering a therapeutically effective amount of a coumarin-3-carboxamide novobiocin analogue. Accordingly, the method can include administering a novobiocin analogue in a therapeutically effective amount for reducing levels of mTOR pathway phosphoproteins P-mTOR, P-Akt and P-S6K, or combinations thereof. Further, the method can include administering a novobiocin analogue in a therapeutically effective amount for reducing levels of Hsp-90 client proteins CFTR, ErbB2, c-Raf and Cdk4, or combinations thereof.
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- Studies towards the synthesis of 13C-labelled anthocyanins
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The anthocyanins are a class of polyphenols found in nature, which are widely distributed throughout the plant kingdom and are thought to possess antioxidant properties. Methodology previously developed in our group for the regioselective placement of 13C-atoms into aromatic rings is being applied to the synthesis of 13C-labelled anthocyanins-namely cyanidin-3-glucoside and delphinidin-3-glucoside. Copyright
- Marshall, Laura J.,Cable, Karl M.,Botting, Nigel P.
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scheme or table
p. 315 - 318
(2011/05/02)
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- High pressure Diels-Alder approach to hydroxy-substituted 6a-cyano-tetrahydro-6H-benzo[c]chromen-6-ones: A route to Δ6- cis-cannabidiol
-
(Chemical Equation Presented) Diels-Alder cycloaddition reactions of 3-cyanocoumarin, hydroxy-substituted 3-cyanocoumarins and mesyl-substituted 3-cyano-coumarins with methyl-1,3-butadienes carried out under high pressure (11 kbar) are reported. Activatio
- Ballerini, Eleonora,Minuti, Lucio,Piermatti, Oriana,Pizzo, Ferdinando
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supporting information; experimental part
p. 4311 - 4317
(2009/09/08)
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- The design, synthesis, and evaluation of coumarin ring derivatives of the novobiocin scaffold that exhibit antiproliferative activity
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(Chemical Equation Presented) Novobiocin, a known DNA gyrase inhibitor, binds to a nucleotide-binding site located on the Hsp90 C-terminus and induces degradation of Hsp90-dependent client proteins at ~700 μM in breast cancer cells (SKBr3). Although many analogues of novobiocin have been synthesized, it was only recently demonstrated that monomeric species exhibit antiproliferative activity against various cancer cell lines. To further refine the essential elements of the coumarin core, a series of modified coumarin derivatives was synthesized and evaluated to elucidate structure-activity relationships for novobiocin as an anticancer agent. Results obtained from these studies have produced novobiocin analogues that manifest low micromolar activity against several cancer cell lines.
- Donnelly, Alison C.,Mays, Jared R.,Burlison, Joseph A.,Nelson, John T.,Vielhauer, George,Holzbeierlein, Jeffrey,Blagg, Brian S. J.
-
experimental part
p. 8901 - 8920
(2009/04/11)
-
- Synthesis and biological evaluation of novel, selective, nonsteroidal glucocorticoid receptor antagonists
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We report the discovery of a novel class of glucocorticoid receptor (GR) antagonists based on the chromene molecular scaffold. The compounds exhibit good functional potency and an improved receptor selectivity profile for GR over other steroid receptors when compared to the classical steroidal GR-antagonist, RU-486.
- Akritopoulou-Zanze, Irini,Patel, Jyoti R.,Hartandi, Kresna,Brenneman, Jehrod,Winn, Martin,Pratt, John K.,Grynfarb, Marlene,Goos-Nisson, Annika,Von Geldern, Thomas W.,Kym, Philip R.
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p. 2079 - 2082
(2007/10/03)
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- Inhibitors of α4 mediated cell adhesion
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The present invention relates to a pharmaceutical composition comprising as an active ingredient a compound of formula (I), wherein Ring A is an aromatic or a heterocyclic ring; Q is a bond, carbonyl, lower alkylene, lower alkenylene, —O-(lower alkylene)-, etc.; n is 0, 1 or 2; Z is oxygen or sulfur, W is oxygen, sulfur, —CH═CH—, —NH— or —N═CH—; R1, R2and R3are the same or different and are hydrogen, halogen, hydroxyl, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted lower alkoxy group, a substituted or unsubstituted amino group, etc.; R4is tetrazolyl, carboxyl group, amide or ester; R5is hydrogen, nitro, amino, hydroxyl, lower alkanoyl, lower alkyl etc.; R6is selected from (a) a substituted or unsubstituted phenyl group, (b) a substituted or unsubstituted pyridyl group, (c) a substituted or unsubstituted thienyl group, (d) a substituted or unsubstituted benzofuranyl group, etc.; or a pharmaceutically acceptable salt thereof.
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-
- Glucocorticoid receptor antagonists for treatment of diabetes
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Compounds of formula I are useful for treating type II diabetes, obesity, hyperglycemia, inadequate glucose clearance, hyperinsulinemia, hypertriglyceridemia, and high-circulating glucocorticoid levels, preparations of the compounds, compositions containing the compounds, and methods of treatment using the compounds.
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-
- Bicyclic compounds
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The present invention is directed to new bicyclic compounds of the formula [I], and pharmaceutically acceptable salts thereof wherein R1, R2, R3, R4, R5, R6, R7, Q1Q2and Q3are as defined in the claims. The compounds have N-myristoyltransferase inhibitory and antifungal activity.
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-
-
- GLUCOCORTICOID RECEPTOR ANTAGONISTS FOR TREATMENT OF DIABETES
-
are useful for treating type II diabetes, obesity, hyperglycemia, inadequate glucose clearance, hyperinsulinemia, hypertriglyceridemia, and high-circulating glucocorticoid levels, preparations of the compounds, compositions containing the compounds, and methods of treatment using the compounds.
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- Silyl triflate-mediated ring-closure and rearrangement in the synthesis of potential bisfuran-containing intermediates of aflatoxin biosynthesis
-
The biosynthetic pathway to the potent mycotoxin aflatoxin B1 is unusually long and complex, proceeding from anthraquinone to xanthone to coumarin nuclear types bearing fused tetrahydro- and bisdihydrofuran rings. A synthetic strategy is described involving two silyl triflate-mediated cyclization and rearrangement processes that have enabled both furofuran oxidation states to be readily achieved and undesired but thermodynamically favorable side reactions to be avoided in the preparation of these ring systems. In the first an o-methoxymethyl phenylacetaldehyde is cyclized directly to the five-membered, differentially protected hemiacetal, while in the second this group, appropriately substituted, can be rearranged to a 4- trialkylsilyloxy-2,5-methano-1,3-benzodioxepane. The latter masked dialdehyde is sufficiently stable to strong base, mild acid, and oxidants to allow all needed aryl ring systems to be constructed. Using these methods, total syntheses of (±)-versicolorin B, (±)-versicolorin A, its hemiacetal, and its 6-deoxy derivative, (±)-6-deoxyversicolorin A, have been achieved, and these are reported herein, as well as preparation of the methyl ester of a putative o-carboxybenzophenone biosynthetic intermediate. In work described elsewhere, incorporation experiments with 13C-labeled forms of these compounds have made possible the complete elucidation of bisfuran biosynthesis characteristic of the first major phase of aflatoxin formation in vivo.
- Graybill, Todd L.,Casillas, Eduard G.,Pal, Kollol,Townsend, Craig A.
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p. 7729 - 7746
(2007/10/03)
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- Methoxymethyl-Directed Aryl Metalation. A Total Synthesis of (+/-)-Averufin
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A total synthesis of (+/-)-averufin, a central intermediate in aflatoxin biosynthesis, is described.The key steps of the synthesis involve the following: (1) the regiospecific coupling of the phthalide anion of 3b and the benzyne derived in situ from aryl
- Townsend, Craig A.,Davis, Steven G.,Christensen, Siegfried B.,Link, John C.,Lewis, Charles P.
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p. 6885 - 6888
(2007/10/02)
-