Heronamides are biosynthetically related metabolites isolated from marine-derived actinomycetes. Heronamide C shows potent antifungal activity by targeting membrane phospholipids possessing saturated hydrocarbon chains with as-yet-unrevealed modes of action. In spite of their curious hypothesized biosynthesis and fascinating biological activities, there have been conflicts in regard to the reported stereochemistries of heronamides. Here, we describe the asymmetric total synthesis of the originally proposed and revised structures of heronamide C, which unambiguously confirmed the chemical structure of this molecule. We also demonstrated nonenzymatic synthesis of heronamides A and B from heronamide C, which not only proved the postulated biosynthesis, but also confirmed the correct structures of heronamides A and B. Investigation of the structure-activity relationship of synthetic and natural heronamides revealed the importance of both long-range stereochemical communication and the 20-membered macrolactam ring for the biological activity of these compounds.

The total synthesis of the proposed structure of heronamide C was accomplished through a Sato–Micalizio reductive alkyne–alkyne coupling strategy and remote‐amine controlled stannylcupration. However, the physical data for the synthetic and natural samples differ from each other, which suggests that the proposed structure should be reinvestigated.

The enantioselective total synthesis of (-)-scabronine G is described. The key features of the present synthesis include the construction of a 5-6 ring system containing two quaternary carbon centers via a diastereoselective intramolecular double Michael reaction and the formation of a seven-membered ring using a Prins cyclization.

Total Synthesis of the Proposed Structure of Heronamide C. -Based on the physical data of the target compound a reinvestigation of the proposed structure of Heronamide C is suggested. -(SAKANISHI, K.; ITOH, S.; SUGIYAMA, R.; NISHIMURA, S.; KAKEYA, H.; IWABUCHI, Y.; KANOH*, N.; Eur. J. Org. Chem. 2014, 7, 1376-1380, http://dx.

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