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Research Article Open access CC BY 4.0

Aromatic Functionalized Indanones and Indanols: Broad Spectrum Intermediates for Drug Candidate Diversification

Thomas C. Nugent, Nilesh N. Shitole

Organics · pp. 263–276 · Published 1 Aug 2024

10.3390/org5030014

Abstract

A series of new aromatic substituted indanone and indanol building blocks have been prepared and are anticipated to aid future drug discovery studies. In total, seven compounds (7, 12–17) are expounded on, and all have been fully characterized. In doing so, we have shown multiple examples of highly chemoselective reactions. One example employed an adaptation of Fujioka’s chemoselective reduction methodology, allowing an ester to be reduced in the presence of a ketone. In another example, an uncommon benzylic methyl group to aldehyde oxidation was demonstrated for two different compounds. These and other chemoselective interconversions allowed us to identify compound (12) as a remarkably flexible springboard for accessing a diverse array of indan-based building blocks (13–17).

Aldehyde Ketone Broad spectrum Diversification (marketing strategy) Chemistry Combinatorial chemistry Organic chemistry Catalysis

References (33)

  1. 1 Schwink, L., Buning, C., Glombik, H., Gossel, M., Kadereit, D., Halland, N., Lohmann, M., Pöverlein, C., and Ritter, K. (2015). Substituted Indanone Compounds as GPR119 Modulators for The Treatment of Diabetes, Obesity, Dyslipidemia, and Related Disorders. (2015150563 A1), WO Patent.
  2. 2 Brea, 2002, New Serotonin 5-HT2A, 5-HT2B, and 5-HT2C Receptor Antagonists: Synthesis, Pharmacology, 3D-QSAR, and Molecular Modeling of (Aminoalkyl)benzo and Heterocycloalkanones [DOI]
  3. 3 Morales, 2004, Synthesis of New 6-Substituted Purinyl-5′-nor-1′-homocarbanucleosides Based on Indanol [DOI]
  4. 4 Alonso, 2008, Synthesis and Antiviral Activities of Novel Purinyl- and Pyrimidinylcarbanucleosides Derived from Indan [DOI]
  5. 5 Gao, 2017, Identification and Preliminary Structure–Activity Relationships of 1-Indanone Derivatives as Novel Indoleamine-2,3-dioxygenase 1 (IDO1) Inhibitors [DOI]
  6. 6 Turek, 2017, Synthesis of 1-Indanones with a Broad Range of Biological Activity [DOI]
  7. 7 Tsai, 1979, A New Synthesis of Chasmanine and 13-Desoxydelphonine: A Preferred Route to the Aromatic Intermediate [DOI]
  8. 8 Roberge, 1979, Convenient Synthesis of Some Highly Functionalized Chromones and Indenones [DOI]
  9. 9 Mazzocchi, 1991, A Regiospecific Synthesis of 8-Methoxy-1,2,3,4,5,6-hexahydro-1,6-methano-3-benzazocines [DOI]
  10. 10 Gan, 2011, An Improved Synthesis of Substituted Indan-1-carboxylic Acid [DOI]
  11. 11 Baddeley, 1953, Interaction of β-Aroylacrylic Acids and Aluminium Chloride [DOI]
  12. 12 Nie, 2022, Facile Access to Chiral Chromanone-2-carboxylic Acids Enabled by Rhodium-Catalyzed Chemo- and Enantioselective Hydrogenation [DOI]
  13. 13 Crompton, 2023, Synthesis of Cyclopropanes via Hydrogen-Borrowing Catalysis [DOI]
  14. 14 Altmann, 2002, The Total Synthesis and Biological Assessment of trans-Epothilone A [DOI]
  15. 15 Yang, 2009, Synthesis and Biological Evaluation of C-12 Triazole and Oxadiazole Analogs of Salvinorin A [DOI]
  16. 16 Lan, 2010, The First Enantioselective Synthesis of Cytotoxic Marine Natural Product Palau’imide and Assignment of Its C-20 Stereochemistry [DOI]
  17. 17 Fujioka, 2011, Reversing the Reactivity of Carbonyl Functions with Phosphonium Salts: Enantioselective Total Synthesis of (+)-Centrolobine [DOI]
  18. 18 Goto, 2012, Effects of Phosphorus Substituents on Reactions of α-Alkoxyphosphonium Salts with Nucleophiles [DOI]
  19. 19 Yahata, 2013, Methodology for in Situ Protection of Aldehydes and Ketones Using Trimethylsilyl Trifluoromethanesulfonate and Phosphines: Selective Alkylation and Reduction of Ketones, Esters, Amides, and Nitriles [DOI]
  20. 20 Ohta, 2017, Chemoselective Reduction and Alkylation of Carbonyl Functions Using Phosphonium Salts as an in Situ Protecting Groups [DOI]
  21. 21 Bhatt, 1981, Facile Conversion of Electron Rich Benzylic Hydrocarbons to Carbonyl Compounds by Peroxydisulfphate and Copper Ions [DOI]
  22. 22 Ohshima, 1992, Synthesis and Antiallergic Activity of 11-(Aminoalkylidene)-6,11-dihydrodibenz[b,e]oxepin Derivatives [DOI]
  23. 23 Hellwinkel, 1987, Dibenzocycloocten-, Dibenzochalcocin- und Diarenochalconindione [DOI]
  24. 24 Sosnovskikh, 2003, Regioselective Nucleophilic 1,4-Trifluoromethylation of 2-Polyfluoroalkylchromones with (Trifluoromethyl)trimethylsilane. Synthesis of Fluorinated Analogs of Natural 2,2-Dimethylchroman-4-ones and 2,2-Dimethylchromenes [DOI]
  25. 25 Liu, 2019, Nickel Chloride-Catalyzed Oxidation of Aromatic Hydrocarbon with Sodium Persulfate at the Benzylic Site [DOI]
  26. 26 Hu, 2019, Bio-Inspired Iron-Catalyzed Oxidation of Alkylarenes Enables Late-Stage Oxidation of Complex Methylarenes to Arylaldehydes [DOI]
  27. 27 Lin, 2018, Chemoselective Oxidation and Deprotection of para-Methoxybenzylic Position with (Diacetoxyiodo)benzene in Acetic-Trifluoroacetic Acid [DOI]
  28. 28 Crawford, 2006, Use of a Highly Effective Intramolecular Pauson–Khand Cyclisation for the Formal Total Synthesis of (±)-α- and β-Cedrene by Preparation of Cedrone [DOI]
  29. 29 Steiner, 2005, Direct Asymmetric α-Fluorination of Aldehydes [DOI]
  30. 30 Brandes, 2006, Non-Biaryl Atropisomers in Organocatalysis [DOI]
  31. 31 Li, 2010, A Facile Method for Synthesis of Polysubstituted Naphthalene Derivatives through Pyrrolidine Catalyzed Domino Reaction [DOI]
  32. 32 Jaiswal, 2013, An Organocatalytic Highly Efficient Approach to the Direct Synthesis of Substituted Carbazoles in Water [DOI]
  33. 33 Caro, 2003, Kinetic Resolution of 3-Hydroxymethylbenzo-cycloalkanols by Selective Asymmetric Hydrogen-Transfer Oxidation [DOI]

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