- HETEROCYCLIC COMPOUNDS AND USES THEREOF
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Provided herein are novel heterocyclic compounds, for example, compounds having Formula I, I-P, II, lI-P, or III. Also provided herein are pharmaceutical compositions comprising the compounds and methods of using the same, for example, in inhibiting aldehyde dehydrogenases and/or for treating various cancers, cancer metastasis, type 2 diabetes, pulmonary arterial hypertension (PAH) or neointimal hyperplasia (NIH).
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- Synthesis of Pharmaceutically Relevant 2-Aminotetralin and 3-Aminochroman Derivatives via Enzymatic Reductive Amination
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2-Aminotetralin and 3-aminochroman derivatives are key structural motifs present in a wide range of pharmaceutically important molecules. Herein, we report an effective biocatalytic approach towards these molecules through the enantioselective reductive coupling of 2-tetralones and 3-chromanones with a diverse range of primary amine partners. Metagenomic imine reductases (IREDs) were employed as the biocatalysts, obtaining high yields and enantiocomplementary selectivity for >15 examples at preparative scale, including the precursors to Ebalzotan, Robalzotan, Alnespirone and 5-OH-DPAT. We also present a convergent chemo-enzymatic total synthesis of the Parkinson's disease therapy Rotigotine in 63 % overall yield and 92 % ee.
- Citoler, Joan,Harawa, Vanessa,Marshall, James R.,Bevinakatti, Han,Finnigan, James D.,Charnock, Simon J.,Turner, Nicholas J.
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p. 24456 - 24460
(2021/10/19)
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- Carbonyl 1,2-transposition through triflate-mediated a-amination
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To date, it remains challenging to selectively migrate a carbonyl oxygen within a given molecular scaffold, especially to an adjacent carbon. In this work, we describe a simple one- or two-pot protocol that transposes a ketone to the vicinal carbon. This approach first converts the ketone to the corresponding alkenyl triflate, which can then undergo the palladium- and norbornene-catalyzed regioselective a-amination and ipso-hydrogenation enabled by a bifunctional hydrogen and nitrogen donor. The resulting "transposed enamine" intermediate can subsequently be hydrolyzed to produce the 1,2-carbonyl-migrated product. This method allows rapid access to unusual bioactive analogs through late-stage functionalization.
- Wu, Zhao,Xu, Xiaolong,Wang, Jianchun,Dong, Guangbin
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p. 734 - 740
(2021/11/16)
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- Bifunctional Br?nsted Base Catalyst Enables Regio-, Diastereo-, and Enantioselective Cα-Alkylation of β-Tetralones and Related Aromatic-Ring-Fused Cycloalkanones
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The catalytic asymmetric synthesis of both α-substituted and α,α-disubstituted (quaternary) β-tetralones through direct α-functionalization of the corresponding β-tetralone precursor remains elusive. A designed Br?nsted base-squaramide bifunctional catalyst promotes the conjugate addition of either unsubstituted or α-monosubstituted β-tetralones to nitroalkenes. Under these reaction conditions, not only enolization, and thus functionalization, occurs at the α-carbon atom of the β-tetralone exclusively, but adducts including all-carbon quaternary centers are also formed in highly diastereo- and enantioselective manner.
- Urruzuno, I?aki,Mugica, Odei,Oiarbide, Mikel,Palomo, Claudio
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p. 2059 - 2063
(2017/02/15)
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- Rh-catalyzed intramolecular aromatic C-H insertion of α-diazo β-ketoesters: Synthesis of 4-carbonyl chroman derivatives
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A Rh-catalyzed intramolecular aromatic C-H insertion of α-diazo β-ketoesters was developed. This protocol offers a practical strategy for the synthesis of 4-carbonyl chroman derivatives with high yield and is compatible with a wide variety of substituents
- Zhang, Xiaolin,Lei, Mei,Zhang, Yi-Nan,Hu, Li-Hong
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p. 3400 - 3406
(2014/05/06)
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- POTENT SMALL MOLECULE INHIBITORS OF AUTOPHAGY, AND METHODS OF USE THEREOF
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Certain aspects of the invention relate to small molecule autophagy inhibitors, and their use for treatment and prevention of cancers and acute pancreatitis. Medicinal chemistry studies led to small molecular autophagy inhibitors with improved potency and selectivity.
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Page/Page column 116; 117
(2014/09/29)
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- Rapid access to chroman-3-ones through gold-catalyzed oxidation of propargyl aryl ethers
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The two-step: Chroman-3-ones are important intermediates for organic synthesis and medicinal chemistry. However, their syntheses require multiple steps and are not efficient. By using gold-catalyzed alkyne oxidation, this versatile heterocycle can be prepared in only two steps from readily available phenols and with mostly high efficiencies (see scheme).
- Wang, Yanzhao,Ji, Kegong,Lan, Sylvester,Zhang, Liming
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p. 1915 - 1918
(2012/03/26)
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- ANTAGONISTS OF THE TRPV1 RECEPTOR AND USES THEREOF
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The present application is directed to compounds that are TRPV1 antagonists and have formula (I) wherein variables Ar1, L1, R1, R2, R3, R4, R5, Y1, Y2, and Y3, are as defined in the description, which are useful for treating disorders caused by or exacerbated by vanilloid receptor activity.
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Page/Page column 13
(2008/12/06)
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- Efficient syntheses of new heteroarotinoids through functional pyridylzinc reagents and palladium-catalyzed cross-coupling reactions
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A convergent synthesis of heteroarotinoids 4, 5a, and 5b, bearing chromene rings in association with pyridyl or ethynylpyridyl moieties, from 6-bromo-2-pyridylzinc chloride (11) is described. This new functional heteroarylzinc reagent, readily accessible
- Alami, Mouad,Peyrat, Jean-Francois,Belachmi, Larbi,Brion, Jean-Daniel
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p. 4207 - 4212
(2007/10/03)
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- STUDIES ON OXYGEN HETEROCYCLES PART-1 : ACID CATALYSED AND PHOTOCHEMICAL REACTIONS OF SOME ARYLDIAZOKETONES
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Trifluoroacetic acid catalysed reaction of 2-methoxyphenyldiazomethylketone (4a), 2-acetoxyphenyldiazomethylketone (4b) and 3-(2-anisyl)-α-diazo-2-propanone (11) leads to the formation of coumaranone (6) and 3-chromanone (12), while 4-(2-anisyl)-α-diazo-2-butanone (16) affords benzo-1-oxepan-3-one (17) and 5-methoxy-2-tetralone (18) in moderate yield.The photochemical decomposition of the said diazoketones (4a, 11 and 16) gave products depending on the length of the side chain present in the substrates.
- Ghosh, Somnath,Datta, Indira,Chakraborty, Rupak,Das, Tapas Kumar,Sengupta, Judhajit,Sarkar, Dipak Chandra
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p. 1441 - 1446
(2007/10/02)
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- PHOTOCHEMICAL BEHAVIOUR OF 3,4-EPOXYPRECOCENE-I AND RELATED EPOXYCHROMANS
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A systematic study of photochemical behaviour of 3,4-epoxyprecocene-I and related epoxychromans was undertaken.Upon irradiation in acetone or cyclohexane, 3,4-epoxyprecocene-I 1 was found to undergo photoisomerisation to the corresponding 3-chromanone 2.In contrast, the photochemical behaviour of analogous 3,4-dihydro-3,4-epoxy-2H-1-benzopyrans 3 was found to be dependent upon the nature of solvent.Irradiation of 3 in cyclohexane led to photodecarbonylation leading to the formation of 2,3-dihydrobenzofurans 4, whereas irradiation in acetone resulted in the formation of chromanones 5.
- Ariamala, G.,Balasubramanian, K. K.
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p. 3769 - 3774
(2007/10/02)
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- CATALYTIC DECOMPOSITION OF BRANCHED α'-PHENOXY-α-DIAZO KETONES AFFORDING 2,8H-CYCLOHEPTAFURAN-3-ONE AND 2H-CYCLOHEPTAFURAN-3a(3aH)METHYL-3-ONE
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The decomposition induced by bis(hexafluoroacetoacetonato)Cu II on branched α-diazo ketones 1 bearing a phenoxy group at the α'-carbon has been investigated.The course of the reactions has been shown to be dependent upon substitution.Mixtures of furanones
- Pusino, Alba,Saba, Antonio,Rosnati, Vittorio
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p. 4319 - 4324
(2007/10/02)
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- Oxidation of Arylalkanols by S2O82--CuII
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Products of oxidation of a series of arylalkanols by S2O82--CuII in acetic acid and acetonitrile are consistent with initial oxidation to aryl radical cations followed by either loss of a benzylic proton or C-C bond scission and subsequent oxidation of intermediate benzylic radicals by CuII to final products. 1-Arylalkanols (ArCHOHR)react by both paths, C-C bond scission increasing with stability of the radical R.. 2-Arylalkanols (ArCH2CHOHR) give chiefly C-C bond scission to benzyl radicals and RCHO.The 3- and 4-arylalkanols undergo chiefly proton loss, and the resulting radicals are oxidized with cyclization to chromans and 2-phenylfurans, respectively, both of which may by oxidized in turn to further products.
- Walling, Cheves,El-Taliawi, Gamil M.,Zhao, Chengxue
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p. 4914 - 4917
(2007/10/02)
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