Total syntheses of (−)-emestrin H and (−)-asteroxepin

First total syntheses of (−)-emestrin H and (−)-asteroxepin are described. To find the appropriate protecting group on the amide nitrogen of the diketopiperazine core, we conducted model studies using a simple diketopiperazine derivative. As a result, allyloxymethyl (Allom) group was the most suitable protecting group, which tolerated Nicolaou's sulfenylation conditions, and was easily cleavable under the mild conditions using Pd(PPh₃)₄ and N,N-dimethylbarbituric acid leaving methylthioethers intact. The general utility of Allom group for protection of amides was studied using simple substrates. Finally, the effectiveness of Allom group was proved by the accomplishment of the first total synthesis of (−)-emestrin H. Allom group was robust enough during installation of two methylthioethers to the diketopiperazine core and easily removed at the final step. The first total synthesis of (−)-asteroxepin was also completed by acylation of (−)-emestrin H.