The asymmetric total synthesis of a newly proposed structure of (3S,16E,20E,23S)-(+)-eushearilide was achieved primarily through an asymmetric Mukaiyama aldol reaction, Schlosser-modified Wittig reaction and 2-methyl-6-nitrobenzoic anhydride-mediated macrolactonization. Based on detailed spectroscopic analyses, the obtained synthetic compound was found to be identical to natural eushearilide. Therefore, we were able to determine the true structure of eushearilide. Moreover, the synthetic compound was found to exhibit significant in vitro antifungal activity against various fungi and bacteria.

An efficient and practical method for the synthesis of (9R,14R,17R)‐FE399, a novel antitumor bicyclic depsipeptide, was developed. A 2‐methyl‐6‐nitrobenzoic anhydride (MNBA)‐mediated dehydration condensation reaction was effectively employed for the formation of the 16‐membered macrocyclic depsipeptide moiety of FE399. FE399 was found to exist as an inseparable equilibrium mixture of conformational isomers; the mixture was quantitatively transformed into the corresponding S‐benzyl product and isolated as a single isomer. Thus, we could confirm that the molecular structure of FE399 obtained by this method is identical to that of the natural product.

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A depsipeptidic analogue of FE399 was efficiently synthesized mainly through macrolactamization using 2-methyl-6nitrobenzoic anhydride (MNBA), and a detailed investigation of the desired 16-membered macrolactam core of FE399 was performed. It was determined that the combination of MNBA and a catalytic amount of 4-(dimethylamino)pyridine N-oxide exhibits much higher activity than that of conventionally used coupling reagents such as hexafluorophosphate azabenzotriazole tetramethyl uronium and benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate.