Article

Download article 		Title: A new approach for the total synthesis of spilanthol and analogue with improved anesthetic activity
Author: Alonso, Isabella G.; Yamane, Lais T.; De Freitas-blanco, Verônica S.; Novaes, Luiz F.T.; Leite, Michelle F.M.B.; De Paula, Eneida; Rodrigues, Marili V.N.; Rodrigues, Rodney A.F.; Pastre, Julio C.
Year: 2018
Is part of: TETRAHEDRON, v. 74, p. 5192 - 5199
DOI: https://doi.org/10.1016/j.tet.2018.06.034

Citation: Alonso, Isabella G.; Yamane, Lais T.; De Freitas-blanco, Verônica S.; Novaes, Luiz F.T.; Leite, Michelle F.M.B.; De Paula, Eneida; Rodrigues, Marili V.N.; Rodrigues, Rodney A.F.; Pastre, Julio C.; A new approach for the total synthesis of spilanthol and analogue with improved anesthetic activity. TETRAHEDRON, v.74, p. 5192-5199, 2018

Abstract: A 5-step synthesis of spilanthol (affinin) is reported, where the route features complete control of alkene geometry during the assembling of the double bonds, with the use of a Sonogashira cross-coupling reaction, a Z-selective alkyne semi-reduction and a HWE olefination reaction as the key steps. A simplified analogue was also prepared in 4 steps. Both compounds were found to permeate dermatomed pig ear skin through an in vitro Franz-type diffusion cell. The simplified analogue presented a superior anesthetic effect in vivo, using the tail flick model, when compared to spilanthol and to the commercial standard EMLA (R). These results suggest that both spilanthol and its analogue could be useful as a topical anesthetic in clinical practice. (C) 2018 Elsevier Ltd. All rights reserved.

Keywords: anesthesia; spilanthol;
Subjects: CIENCIAS_BIOLOGICAS; Farmacologia Bioquímica e Molecular;

Funding: The authors acknowledge financial support from the Sao Paulo Research Foundation - FAPESP (Awards No. 2014/26378-2, 2014/25770-6, 2014/16186-9, 2014/06461-2 and 2015/08199-6), CNPq (award No. 453862/2014-4), and CAPES. We are also grateful to Renan Galaverna and Prof. Marcos Eberlin (University of Campinas, Brazil) for HRMS analysis. This work is dedicated in memory of Sir Derek Barton on occasion of his centennial birthday. 		Financed by: