54621-12-4Relevant articles and documents
A concise total synthesis of (±)-minfiensine
Liu, Peijun,Wang, Juan,Zhang, Jiancun,Qiu, Fayang G.
, p. 6426 - 6428 (2011)
A concise total synthesis of (±)-minfiensine using all conventional methods and starting from commercial materials has been completed. The synthesis features a Fischer indole synthesis, a Heck alkylation of an intermediate ketone enolate, conversion of a ketone carbonyl into an epoxide, and transformation of the latter into an allylic alcohol.
ABC ! ABCE/D based approaches to the pentacyclic ring system of the vinca alkaloids using intramolecular hetero-[2+2]cycloaddition and gold(i)-catalysed 6-endo-dig cyclisation protocols
White, Lorenzo V.,Banwell, Martin G.,Willis, Anthony C.
, p. 298 - 315 (2015)
The angularly substituted tetrahydrocarbazole 13, which is readily obtained from cyclohexane-1,4-dione monoethylene ketal (6) using Fischer indole chemistry, has been converted into the isothiocyanate 16. Photolysis of this last compound affords, via an intramolecular hetero-[2+2]cycloaddition reaction, the pentacyclic "-thiolactam 17 that incorporates the ABCE ring substructure of natural products 1-3. Attempts to effect a two-carbon homologation of the four-membered ring within compound 17, and thereby establish the D-ring, failed. The azide 20, also obtained from compound 13, forms the cyclic imine 21 on thermolysis in refluxing toluene and the readily derived enamide 23 engages in a Au(I)-catalysed 6-endo-dig cyclisation reaction to give compound 24 embodying the ABCDE ring system of the title alkaloids.
Direct Synthesis of Indoles from Azoarenes and Ketones with Bis(neopentylglycolato)diboron Using 4,4′-Bipyridyl as an Organocatalyst
Misal Castro, Luis C.,Sultan, Ibrahim,Nishi, Kohei,Tsurugi, Hayato,Mashima, Kazushi
, p. 3287 - 3299 (2021/03/01)
Multifunctionalized indole derivatives were prepared by reducing azoarenes in the presence of ketones and bis(neopentylglycolato)diboron (B2nep2) with a catalytic amount of 4,4′-bipyridyl under neutral reaction conditions, where 4,4′-bipyridyl acted as an organocatalyst to activate the B-B bond of B2nep2 and form N,N′-diboryl-1,2-diarylhydrazines as key intermediates. Further reaction of N,N′-diboryl-1,2-diarylhydrazines with ketones afforded N-vinyl-1,2-diarylhydrazines, which rearranged to the corresponding indoles via the Fischer indole mechanism. This organocatalytic system was applied to diverse alkyl cyclic ketones, dialkyl, and alkyl/aryl ketones, including heteroatoms. Methyl alkyl ketones gave the corresponding 2-methyl-3-substituted indoles in a regioselective manner. This protocol allowed us to expand the preparation of indoles having high compatibility with not only electron-donating and electron-withdrawing groups but also N- and O-protecting functional groups.
LIPOXYGENASE INHIBITORS
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Paragraph 00568-00570, (2021/10/02)
Various embodiments of the present disclosure are directed to compounds having Formula (I), Formula (IA), Formula (IB), Formula (IC), Formula (ID), Formula (IE), and/or pharmaceutically acceptable salts thereof. The compounds can be suitable for inhibiting lipoxygenases, and/or treating associated diseases, such as Alzheimer's disease. In some embodiments, the compounds may be administered to a patient as part of a pharmaceutical formulation.
Selective N1/N4 1,4-Cycloaddition of 1,2,4,5-Tetrazines Enabled by Solvent Hydrogen Bonding
Zhu, Zixi,Glinkerman, Christopher M.,Boger, Dale L.
supporting information, p. 20778 - 20787 (2020/12/22)
An unprecedented 1,4-cycloaddition (vs 3,6-cycloaddition) of 1,2,4,5-tetrazines is described with preformed or in situ generated aryl-conjugated enamines promoted by the solvent hydrogen bonding of hexafluoroisopropanol (HFIP) that is conducted under mild reaction conditions (0.1 M HFIP, 25 °C, 12 h). The reaction constitutes a formal [4 + 2] cycloaddition across the two nitrogen atoms (N1/N4) of the 1,2,4,5-tetrazine followed by a formal retro [4 + 2] cycloaddition loss of a nitrile and aromatization to generate a 1,2,4-triazine derivative. The factors that impact the remarkable change in the reaction mode, optimization of reaction parameters, the scope and simplification of its implementation through in situ enamine generation from aldehydes and ketones, the reaction scope for 3,6-bis(thiomethyl)-1,2,4,5-tetrazine, a survey of participating 1,2,4,5-tetrazines, and key mechanistic insights into this reaction are detailed. Given its simplicity and breath, the study establishes a novel method for the simple and efficient one-step synthesis of 1,2,4-triazines under mild conditions from readily accessible starting materials. Whereas alternative protic solvents (e.g., MeOH vs HFIP) provide products of the conventional 3,6-cycoladdition, the enhanced hydrogen bonding capability of HFIP uniquely results in promotion of the unprecedented formal 1,4-cycloaddition. As such, the studies represent an example of not just an enhancement in the rate or efficiency of a heterocyclic azadiene cycloaddition by hydrogen bonding catalysis but also the first to alter the mode (N1/N4 vs C3/C6) of cycloaddition.
Synthesis method for (R)-3-amino-1,2,3,4-tetrahydrocarbazole
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Paragraph 0038; 0039; 0040; 0041, (2016/10/08)
The invention discloses a synthesis method for a Ramatroban intermediate (R)-3-amino-1,2,3,4-tetrahydrocarbazole.The synthesis method includes the steps that 1,4-cyclohexanedione monoethylene acetal and phenylhydrazine are subjected to aldehyde ketone amine condensation, then cyclization is conducted to obtain 3,3-vinyl dioxo-1,2,4,9-tetrahydrocarbazole-3-ketone, then protecting groups are removed to obtain 1,2,4,9-tetrahydrocarbazole-3-ketone, 1,2,4,9-tetrahydrocarbazole-3-ketone and O-hydroxylamine hydrochloride react to obtain oxime ether, and oxime ether is subjected to low-temperature chiral selective reduction to directly obtain (R)-3-amino-1,2,3,4-tetrahydrocarbazole.A new synthesis route of the important intermediate (R)-3-amino-1,2,3,4-tetrahydrocarbazole of medicine Ramatroban is provided.The synthesis method is simple and convenient, operation conditions are mild, the reaction yield is high, an amplification reaction can be conducted, and the synthesis method is applied to industrial production.
Enantioselective Total Synthesis of (+)-Hinckdentine A via a Catalytic Dearomatization Approach
Douki, Kazuya,Ono, Hiroyuki,Taniguchi, Tohru,Shimokawa, Jun,Kitamura, Masato,Fukuyama, Tohru
supporting information, p. 14578 - 14581 (2016/11/18)
Optically pure hinckdentine A was synthesized on a 300 mg scale via an asymmetric catalysis-based strategy. The key steps to the first asymmetric synthesis involved (i) enantioselective dearomative cyclization of an achiral N-acyl indole that allowed for the efficient construction of the key polycyclic indoline intermediate with a crucial tetrasubstituted stereogenic carbon center, (ii) Beckmann fragmentation-mediated ring expansion, (iii) rearrangement-based introduction of an anilinic nitrogen atom, (iv) regioselective tribromination, and (v) final closure of the cyclic amidine moiety.
HETEROARYL COMPOUNDS FOR KINASE INHIBITION
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Paragraph 00408, (2016/12/01)
Compounds and pharmaceutical compositions that modulate kinase activity, including mutant EGFR and mutant HER2 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including mutant EGFRand mutant HER2 activity, are described herein.
Asymmetric chemoenzymatic synthesis of ramatroban using lipases and oxidoreductases
Busto, Eduardo,Gotor-Fernandez, Vicente,Gotor, Vicente
experimental part, p. 4842 - 4848 (2012/07/31)
A chemoenzymatic asymmetric route for the preparation of enantiopure (R)-ramatroban has been developed for the first time. The action of lipases and oxidoreductases has been independently studied, and both were found as excellent biocatalysts for the production of adequate chiral intermediates under very mild reaction conditions. CAL-B efficiently catalyzed the resolution of (±)-2,3,4,9-tetrahydro-1H-carbazol-3-ol that was acylated with high stereocontrol. On the other hand, ADH-A mediated bioreduction of 4,9-dihydro-1H-carbazol-3(2H)-one provided an alternative access to the same enantiopure alcohol previously obtained through lipase-catalyzed resolution, a useful synthetic building block in the synthesis of ramatroban. Inversion of the absolute configuration of (S)-2,3,4,9-tetrahydro-1H-carbazol-3-ol has been identified as a key point in the synthetic route, optimizing this process to avoid racemization of the azide intermediate, finally yielding (R)-ramatroban in enantiopure form by the formation of the corresponding amine and the convenient functionalization of both exocyclic and indole nitrogen atoms.
TRICYCLIC CYTOPROTECTIVE COMPOUNDS
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Page/Page column 18-19, (2008/06/13)
Compounds of formula (I): in which: X is a group of formula >CR1R2 or >SO2; Y is a group of formula >NH or >CR1R2; Z is a group of formula >C=O or >CH2 or a direct bond; R1 hydrogen and R2 is hydrogen, carboxy or hydroxy; or R1 and R2 together represent an oxo group, a methylenedioxy group or a hydroxyimino group; R3 is hydrogen or lower alkyl; R4 represents two hydrogen atoms, or an oxo or hydroxyimino group; R5 is hydrogen, lower alkyl or halogen; R6 is hydrogen, lower alkoxy or carboxy; R7 and R8 are each hydrogen, lower alkyl or halogen; and pharmaceutically acceptable salts and esters thereof can be used for the treatment or prophylaxis of acute or chronic neurodegenerative diseases or conditions such as Alzheimer’s Disease, Parkinson’s Disease, Huntington’s Chorea, Multiple Sclerosis or the sequelae to acute ischaemic events such as heart attack, stroke or head injury and for protection against ischaemic damage to tissues of peripheral organs.
