Research Publications
(Journal Articles, Patents, Book Chapters)
"1,2-Wagner Meerwein Shift in Divergent Reactivity of 1-Azapentadienyl Cations Yields Expedient Access to Highly Substituted Pyrroles and Indenes" - D. D. Gaonkar, S. Gangai, K. Mhaske, R. Narayan* in preparation, 2023.
"Cu(II)-Catalyzed Aerobic Oxidative Coupling of Furans with Indoles Enables Expeditious Synthesis of Indolyl-Furans with Blue Fluorescence" - S. Gangai, R. Fernandes, K. Mhaske, R. Narayan*, RSc. Advances, 2024, 14, 1239-1249. (First two authors contributed equally)
DOI: 10.1039/d3ra08226a
Sustainability is increasingly being factored into the design of chemical processes. Herein, we report the oxidative coupling between indoles and furans using extremely inexpensive catalyst CuCl2.2H2O (<0.25$ per g) in the presence of air for an expeditious synthesis of indolyl–furans. The reaction was found to work even under partially aqueous conditions. In addition, the methodology provides direct access to novel indole–furan–thiophene (IFT)-based electron-rich pi-conjugated systems, which show green-yellow fluorescence with large Stokes shift and high quantum yields.
"Aerobic Catalytic Cross-Dehydrogenative Coupling of Furans with Indoles Provides Access to Fluorophores with Large Stokes Shift" - K. Mhaske, S. Gangai, R. Fernandes, A. Kamble, A. Chowdhury, R. Narayan*, Chem. Eur. J., 2024, e202302929.
We report a general cross-dehydrogenative coupling between furans and indoles using earth-abundant metal catalyst FeCl3.6H2O in presence of oxygen. The reaction displayed scalability and aqueous compatibility, thus making it practical, operationally simple, and sustainable. The products were found to possess fluorescence properties with remarkable Stokes’ shift of upto 205 nm.
"Mapping the Lipid Signatures in COVID-19: Diagnostic and Therapeutic Solutions" - A. Dasgupta, S. Gangai, R. Narayan*, S. Kapoor*, J. Med. Chem., 2023, 66, 14411 - 14433.
SARS-CoV-2, the virus responsible for COVID-19, hijacks the metabolic machinery of the host cells, relying on their lipids and lipoproteins for entry, trafficking, immune evasion, viral replication, and exocytosis. The infection causes host cell lipid metabolic remodelling. Targeting lipid-based processes is, thus, a promising strategy for countering COVID-19. Here, we review the role of lipids in the different steps of the SARS-CoV-2 pathogenesis and identify lipid-centric targetable avenues. We summarize the emerging direct and indirect therapeutic approaches for targeting COVID-19 using lipid-inspired approaches.
"Computational Benchmarking of Putative KIFC1 Inhibitors" - N. Sharma, D. Setiawan, D. Hamelberg, R. Narayan* and R. Aneja * Med. Res. Rev. 2023, 43, 293 - 318.
The paper describes the first-of-its-kind computational benchmarking of all known KIFC1 inhibitors against all the three proposed binding sites using the most resolved KIFC1 structural information. In addition, the most comprehensive review of the putative KIFC1 inhibitors reported to date in the literature is also presented along with a detailed analysis of the evolving biological profiles of each inhibitor chemotype. In this work, we show that α4/α6 is the most preferred binding site for the known KIFC1 inhibitors. Identification of the challenges in the development of novel KIFC1 inhibitors has been added to complete the review.
"The Pseudo Natural Product Rhonin Targets RhoGDI" - M. Akbarzadeh, J. Flegel, S. Patil, E. Shang, R. Narayan, M. Buchholzer, N. S. Kazemein Jasemi, M. Grigalunas, A. Krzyzanowski, D. Abegg, A. Shuster, M. Potowski, H. Karatas, G. Karageorgis, N. Mosaddeghzadeh, M.-L. Zischinsky, C. Merten, C. Golz, L. Brieger, C. Strohmann, A. P. Antonchick, P. Janning, A. Adibekian, R. S. Goody, M. Reza Ahmadian, S. Ziegler, H. Waldmann * Angew Chem. Intl. Ed. 2022, 61(18), e202115193.
DOI: https://doi.org/10.1002/anie.202115193 (Open Access)
Selected as the "Hot Paper" by the editors.
The identification of the pseudo-natural product Rhonin as the first small-molecule modulator of RHO GDP dissociation inhibitor (RHOGDI) is reported. Rhonin binds to RHOGDI and interferes with its function by disrupting the interaction between RHOGDI and RHO GTPases.
“Copper Catalyzed Aerobic Cross-Dedrogenative Coupling of β-Oxime Ether Furan with Indole" – R. Fernandes, K. A. Mhaske, R. Balhara, G. Jindal and R. Narayan* Chem. Asian. J. 2022, 17(6), e202101369. (First two authors contributed equally.)
Furan and Indole represent two of the most versatile heterocycles in organic chemistry. Herein, we report the first cross-dehydrogenative coupling of these two heterocycles catalyzed by copper in combination with aerial oxygen. Additionally, we also demonstrate a lesser known activating group effect of oxime ether substituent in oxidative coupling.
"Mycobacteria Membranes as Actionable Target in Lipid-Centric Therapy in Tuberculosis" - B. Modak, S. Girkar, R. Narayan* and S. Kapoor* J. Med. Chem. 2022, 65, 3046-3065.
Infectious diseases remain significant health concerns worldwide, and resistance is particularly common in patients with tuberculosis caused by Mycobacterium tuberculosis. Here, we comprehensively review recent advances in the development of membrane-active chemotypes that target mycobacterial membranes and discuss clinically relevant membrane-active antibacterial agents that have shown promise in counteracting bacterial infections. We discuss the relationship between the membrane properties and the synthetic requirements within the chemical scaffold, as well as the limitations of current membrane-active chemotypes.
"β-Bromoenol Phosphate as a New Precursor for the Modular Regioselective Synthesis of Substituted Furans" - R. Fernandes, K. Mhaske and R. Narayan* Tetrahedron 2022, 103, 132553. (First two authors contributed equally)
DOI: https://doi.org/10.1016/j.tet.2021.132553
Featured in Org. Chem. Highlights (17th Oct 2022)
Furan occupies a position of eminence among heterocycles. Despite the availability of many methodologies for the synthesis of variably substituted furans, a modular convenient synthesis of 2,4-disubstituted furans remains challenging. The present work attempts to bridge that gap through a novel annulation-based approach using methyl ketones and β-bromoenol phosphates. We have demonstrated a hitherto unknown reactivity of β-bromoenol phosphates which is responsible for the observed regioselectivity. The methodology was applied to obtain synthetically challenging 3-acylfuran derivatives as well.
"Dynamical Organization of Compositionally Distinct Inner and Outer Membrane Lipids of Mycobacteria"- P. Adhyapak, A. T. Srivatsav, M. Mishra, A. Singh, R. Narayan, and S. Kapoor, Biophysical Journal, 2020, 118, 1279-1291.
DOI: https://doi.org/10.1016/j.bpj.2020.01.027
“Chemical Tools for Illumination of Tuberculosis Biology, Virulence Mechanisms, and Diagnosis’’ – G. Kumar, R. Narayan*, and S. Kapoor* J. Med. Chem. 2020, 63, 15308-15332.
“Enantioselective Catalysis using Copper (I)-Phosphine Complexes’’ – R. Narayan* in “Copper(I) Chemistry of Phosphines, Functionalised Phosphines and Phosphorus Heterocycles” M. S. Balakrishna (Ed.), Elsevier, 2019, pp 259-303.
‘‘The Pseudo Natural Product Myokinasib Is a Myosin Light Chain Kinase 1 Inhibitor with Unprecedented Chemotype’’ –T. Schneidwand, S. Kapoor, G. Garivet, G. Karageorgis, R. Narayan, G-V. Navarro, A. P. Antonchick, S. Ziegler and H. Waldmann*, Cell Chem. Bio. 2019, 26, 512-523.e5.
DOI: https://doi.org/10.1016/j.chembiol.2018.11.014 (Open Access)
Small-molecule chemotypes with unexpected bioactivity may be identified by combining strategies built on the biological relevance of natural products (NPs). Evaluation in target-agnostic phenotypic assays and target identification may link biologically relevant chemotypes to unexpected and unknown targets. We describe the phenotypic identification of an unprecedented kinase inhibitor chemotype, termed Myokinasib which impairs cytokinesis, induces formation of multinucleated cells, and reduces phosphorylated myosin II light chain abundance on stress fibers by selective inhibition of myosin light chain kinase 1.
Biocon Bristol Myers Squibb Research Center (BBRC) Bangalore, India
"Bridged Bicyclic Compounds as Farnesoid X Receptor Modulators" WO/US Patent Application, Application Number 62/580075. Granted on 09th May 2019 as US20190127358A1 and WO2019089667A1.
"Substituted Bicyclic Compounds as Farnesoid X Receptor Modulators" WO/US Patent Application, Application Number 62/806066. Granted on 08th Aug 2020 as WO/2020/168148. Granted on 08th Aug 2020 as WO/2020/168148.
"Substituted Bicyclic Compounds as Farnesoid X Receptor Modulators" WO/US Patent Application, Application Number 62/806042. Granted on 08th Aug 2020 as WO/2020/168143.
"Substituted Amide Compounds Useful as Farnesoid X Receptor Modulators" WO/US Patent Application, Application Number 62/806047. Granted on 08th Aug 2020 as WO/2020/168152.
"Substituted Amide Compounds Useful as Farnesoid X Receptor Modulators" WO/US Patent Application, Application Number 62/806060. Granted on 08th Aug 2020 as WO/2020/168149.
Supervised Career (Max Planck Institute (MPI) Dortmund, Germany & WWU Muenster, Germany)
‘‘Metal-Free Oxidative C-C Bond Formation Through C-H Bond Functionalization’’- R. Narayan, K. Matcha, and A. P. Antonchick, Chem. Eur. J. 2015, 21, 14678-14693.
- The most read article from ChemPubSoc Europe Journals for October 2015
- One of the most accessed articles in first year after publication
‘‘Hypervalent Iodine (III) in Direct C-H Bond Functionalization’’– R. Narayan, S. Manna, and A. P. Antonchick*, Synlett, 2015, 26, 1785-1803.
- One of the most read articles in June 2015
‘‘Regioselective Annulation of Nitrosopyridine with Alkynes: Straightforward Synthesis of N-Oxide Imidazopyridines’’ - S. Manna, R. Narayan, C. Golz, C. Strohman, and A. P. Antonchick*, Chem. Comm. 2015, 51, 6119-6122.
‘‘Direct Regioselective Amination of Chromones Exposes Potent Inhibitors of Hedgehog Signaling Pathway’’ - R. Samanta, R. Narayan, J. O. Bauer, C. Strohmann, S. Sievers and A. P. Antonchick*, Chem. Comm. 2015, 51, 925-928.
‘‘2,2’-Diiodobiphenyl’’ - R. Narayan, and A. P. Antonchick*, Electronic Encyclopedia of Reagents For Organic Synthesis (e-EROS); J. Wiley and Sons, 2014.
‘‘Catalytic Enantioselective 1,3-Dipolar Cycloadditions of Azomethine Ylides for Biology- Oriented Synthesis’’ - R. Narayan, M.Potowski, Z.-J. Jia, A. P. Antonchick*, and H. Waldmann *, Acc. Chem. Res. 2014, 47, 1296-1310.
- American Chemical Society (ACS) ‘‘Editors’ Choice’’ article
- One of the most read articles in 4/2014-5/2014 and in first 12 months after publication
‘‘Hypervalent Iodine-Mediated Selective Oxidative Functionalization of (Thio)Chromones with Alkanes’’ - R. Narayan, and A. P. Antonchick*, Chem. Eur. J. 2014, 20, 4568-4572.
- One of the most read articles in 03/2014 and in the first year of publication
‘‘Catalytic Enantioselective Synthesis of Functionalized Tropanes Reveals Novel Inhibitors of Hedgehog Signaling’’ - R. Narayan, J. O. Bauer, C. Strohmann, A. P. Antonchick*, and H. Waldmann*, Angew. Chem. Int. Ed. 2013, 52, 12892-12896.
- Selected as ‘Hot Paper’ by the editors of Angewandte Chemie Int. Ed.
- Highlighted in Synfacts, 2014, 272
- Cheminform ‘Editors’ Choice’ article for 05/2014.
‘‘Metal-Free Radical Azidoarylation of Alkenes: Rapid Access to Oxindoles by Cascade C-N and C-C bond Forming Reactions’’ - K. Matcha, R. Narayan, and A. P. Antonchick*, Angew. Chem. Int. Ed. 2013, 52, 7985-7989.
‘‘Rhodium(III)-Catalyzed Direct Oxidative Cross-Coupling at the C-5 Position of Chromone with Alkenes’’ - R. Samanta, R. Narayan, and A. P. Antonchick*, Org. Lett. 2013, 14, 6108-6111.
‘‘Preparation of N-H Pyrroles under Superelectrophilic Conditions through an Aza- Nazarov Reaction Cascade with Indole as Neutral Leaving Group: Experiment and Theory ’’ - R. Narayan, C.-G. Daniliuc, and E.-U. Würthwein*, Eur. J. Org. Chem. 2012, 6021-6032.
‘‘Synthesis of Pyrroles through a 4π-Electrocyclic Ring-Closure Reaction of 1-Azapentadienyl Cations’’ - R. Narayan, R. Fröhlich, and E.-U. Würthwein*, J. Org. Chem. 2012, 77, 1868-1879.
‘‘3-(Hetero)aryl-4-indolylamino-α-Tetralones by Diastereoselective Internal Redox Cyclization: An ‘Azaenamine’ Conjugate Addition’’ - N. Ghavtadze*, R. Narayan, B. Wibbeling, and E.-U. Würthwein*, J. Org. Chem. 2011, 76, 5185-5197.
- Selected as ‘Featured Article’ by the editors