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Unusual pharmacophores. Chemical reactions underlie the biological mechanisms of many small molecules. Insight into chemical reactivity can therefore inform biology. Our laboratory has invented methods to easily access several classes of secondary metabolites that contain unique pharmacophores and whose covalent cellular reactivity is not understood. We are working to understand 1) the Nuphar dimers, which contain a covalently-reactive thiaspirane pharmacophore; 2. the asmarine alkaloids, whose N-hydroxydiazepine purine may bind metals, react covalently or oxidize a biomolecule; and 3. the isocyanoterpenes (ICTs), antimalarial marine metabolites whose isonitrile function may affect diverse bioinorganic processes. To study this latter class, we invented a general stereochemical inversion of tertiary alcohols. 

 

See publications: 

  1. Huffman, B. J.; Chen, S.; Schwarz, J. L; Plata, R. E.; Chin, E.; Houk, K. N.; Lairson, L. L.; Shenvi, R. A. "Electronic Complementarity Permits Hindered Butenolide Heterodimerization and Discovery of Novel cGAS/STING Pathway Antagonists," Nature Chem. 2020, 12, 310–317.

  2. Lambrecht, M.; Kelly, J. W.; Shenvi, R. A. "Mechanism of Action of the Cytotoxic Asmarine Alkaloids." ACS Chem. Bio. 2018, 13, 1299–1306. DOI 10.1021/ acschembio.8b00096.

  3. Martinez, R.; Burdge, H.; Shenvi, R. A. Reanalysis of Lindenatriene, a Building Block for the Synthesis of Lindenane Oligomers, [invited manuscript, award issue, Symposium-in-Print] Tetrahedron 2019, 75, 3140–3144.

  4. Reiher, C. A.; Shenvi, R. A. "Stereocontrolled Synthesis of Kalihinol C" JACS, 2017, 139, 3647–3650.

  5. Tada, N.; Jansen, D. J.; Mower, M. P.; Blewett, M. M.; Umotoy, J. C.; Cravatt, B. F.; Wolan, D. W.; Shenvi, R. A. "Synthesis and Sulfur Electrophilicity of the Nuphar Thiaspirane Pharmacophore," A(CS)2 2016, 2, 401–408

  6. Lu, H.-H.; Pronin, S. V.; Antonova-Koch, Y.; Meister, S.; Winzeler, E. A.; Shenvi, R. A. "Synthesis of (+)-7,20-Diisocyanoadociane and Liver Stage Antiplasmodial Activity of the ICT Class," JACS 2016, 138, 7268–7271

  7. Jansen, D. J.; Shenvi, R. A. "Synthesis of (–)-Neothiobinupharidine", JACS, 2013, 135, 1209-1212.

  8. Wan, K. K.; Iwasaki, K.; Umotoy, J. C.; Wolan, D.; Shenvi, R. A. “Nitrosopurines en route to Potent Asmarine Cytotoxins” Angew. Chem. Int. Ed. 2015, 127, 2440-2445.

  9. Pronin, S. V.; Shenvi, R. A. “Synthesis of a Potent Antimalarial Amphilectene”, JACS. 2012, 134, 19604-19606.

  10. Pronin, S. V.; Reiher, C. A.; Shenvi, R. A. "Stereoinversion of tertiary alcohols to tertiary-alkyl isonitriles and amines", Nature, 2013, 501, 195-199.

  11. Pronin, S. V.; Shenvi, R. A. “Synthesis of Highly Strained Terpenes by Nonstop Tail-to-Head Polycyclization”, Nature Chem. 2012, 4, 915-920.

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