Sanphetchaloemchok P.Saikachain N.Khumjiang R.Muanprasat C.Tadpetch K.Mahidol University2023-05-192023-05-192023-04-03European Journal of Organic Chemistry Vol.26 No.13 (2023)1434193Xhttps://repository.li.mahidol.ac.th/handle/20.500.14594/81741The first total syntheses of seiricuprolide and pestalotioprolide B, rare 14-membered α,β-unsaturated macrolides embedding a chiral epoxide motif, were achieved in 17 steps with 1.9 % and 1.6 % overall yields, respectively. Our synthesis featured the key Shiina macrolactonization to construct the 14-membered macrocyclic skeleton, Wittig olefination to generate the (E)-α,β-unsaturated ester and selective reduction of advanced chiral propargylic alcohol intermediate to enable the exclusive formation of Z- or E-olefin at C8−C9. Synthetic seiricuprolide and pestalotioprolide B were evaluated for their cytotoxic activity against the HCT116 colon cancer cell line as well as their inhibitory effect on CFTR chloride channel activity in human intestinal epithelial (T84) cells. Preliminary structure–activity relationship suggested that the C5−C6 β-epoxide moiety suppressed both biological activities.ChemistryArticleSCOPUS10.1002/ejoc.2023000342-s2.0-8514904410510990690