Abstract
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.
Highlights
A novel bicyclic depsipeptide, FE399 (1), was first isolated from the filamentous fungus, Ascochyta sp., by Oobayashi et al of the Ajinomoto group[1]
We report the total synthesis of (9R,14R,17R)-FE399 (1) mainly by using the methyl-6-nitrobenzoic anhydride (MNBA)-mediated dehydration condensation reaction for the construction of the
We have achieved the total synthesis of (9R,14R,17R)-1 through a macrolactamization approach using methyl-6-nitrobenzoic anhydride (MNBA) in the presence of a nucleophilic catalyst, such as DMAP or DMAPO, without any epimerization of the stereogenic centers of 1 from a known alcohol 5 in[15] steps, with an overall yield of 20%
Summary
A novel bicyclic depsipeptide, FE399 (1), was first isolated from the filamentous fungus, Ascochyta sp., by Oobayashi et al of the Ajinomoto group[1] (see Figure 1). The total synthesis of (9R,14R,17R)-FE399 (1) was efficiently achieved through a macrolactamization approach mainly by exploiting the MNBA-mediated dehydration condensation reaction for the construction of the 16-membered depsipeptide core of FE399 using a known diol (5) in 15 steps, with an overall yield of 20%. After the solution was stirred at room temperature for 2 h, the reaction mixture was quenched with saturated aqueous ammonium chloride.
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