Search

Amphidinolides C, F, and U, including C2‐C4 analogs, are highly cytotoxic marine macrolides, mainly isolated from dinoflagellates of the genus Amphidinium. All these polyketides share a 75 % or more similar structure, highlighted by a macrolactone ring, at least one trans‐2,5‐substituted‐THF motif and a characteristic polyenic side chain. From their isolation and absolute configurational assignment, the total synthesis of these marine macrolides represented an intense challenge to the organic synthesis community over the last 15 years, with around 14 research groups engaged in this inspiring task. In the first part of this review, we present the different approaches to the isolation and characterization of these natural products, including the most recent analogs, which may cast doubt on the biogenetic origin of these compounds. The various synthetic approaches to the total synthesis of C, F, and U amphidinolides are presented in a second part, focusing on key reactions and/or innovative strategies. The review concludes in a third section summarizing the successful approaches leading to the total synthesis of one of the members of this amphidinolide subfamily. [ABSTRACT FROM AUTHOR]

Keywords: amphidinolides; polyketides; total synthesis; Suzuki cross-coupling; epoxides; protecting groups EN amphidinolides polyketides total synthesis Suzuki cross-coupling epoxides protecting groups 2017 2021 5 10/09/23 20231024 NES 231024 Graph Amphidinolide U is a moderately cytotoxic macrolide isolated from dinoflagellates of an I Amphidinium i species, with reported IC SB 50 sb values on L1210 and KB cell lines of 12 and 20 g/mL, respectively. 1994, 107 24 Ley, S V. Tackett, M N. Maddess, M L. Anderson, J C. Brennan, P E. Cappi, M W. Heer, J P. Helgen, C. Kori, M. Kouklovsky, C. Marsden, S P. Norman, J. Osborn, D P. Palomero, M. Á. Pavey, J B. J. Pinel, C. Robinson, L A. Schnaubelt, J. Scott, J S. Spilling, C D. Watanabe, H. Wesson, K E. Willis, M C. Chem. Eur. J. 2009, 15: 2874 25 Cid, M B. Pattenden, G. Synlett. Chem. 2006, 71: 5826 20 Mihelich, E D. Daniels, K. Eickhoff, D J. J. Am. Chem. Soc. 1981, 103: 7690 21 Corey, E J. Fuchs, P L. Tetrahedron Lett. Int. Ed. 2001, 40: 4544 29 Berthold, D. Breit, B. Chem. Eur. J. 2018, 24: 16770 30 Geist, E. Kirschning, A. Schmidt, T. Nat. [Extracted from the article]

Natural products (NPs) are endless sources of compounds for fighting against several pathologies. Many dysfunctions, including cardiovascular disorders, such as cardiac arrhythmias have their modes of action regulation of the concentration of electrolytes inside and outside the cell targeting ion channels. Here, we highlight plant extracts and secondary metabolites' effects on the treatment of related cardiac pathologies on hERG, Nav, and Cav of cardiomyocytes. The natural product's pharmacology of expressed receptors like alpha-adrenergic receptors causes an influx of Ca 2+ ions through receptor-operated Ca 2+ ion channels. We also examine the NPs associated with cardiac contractions such as myocardial contractility by reducing the L-type calcium current and decreasing the intracellular calcium transient, inhibiting the K + induced contractions, decreasing amplitude of myocyte shortening and showed negative ionotropic and chronotropic effects due to decreasing cytosolic Ca 2+ . We examine whether the NPs block potassium channels, particular the hERG channel and regulatory effects on Nav1.7.