Total Synthesis of Reniochalistatin E

Abstract

Reniochalistatin E (1) is one of the five related cyclic peptides isolated from the marine sponge Reniochalina stalagmitis. The discovery of these compounds resulted from a screening program directed toward the identification of proline-rich bioactive compounds. Reniochalistatin E is the only member of the family to possess a tryptophan amino acid residue. Given the cytotoxicity observed for 1, efforts were directed toward developing a synthetic route to 1. The first total synthesis of 1 has been accomplished in a 15-step route in an overall 5.0% yield. The synthetic sample of reniochalistatin E was shown to have similar activity toward HeLa and RPMI-8226 cell lines compared to the natural sample, with IC values of 16.9 vs 17.3 μM and 4.5 vs 4.9 μM, respectively. Interestingly, both of the fully deprotected octapeptides constructed toward the synthesis of reniochalistatin E were shown to have cytotoxicity. The route provides a means to probe the structure-activity relationship of 1 and further biological investigations.

Total Synthesis and Bioactivity Evaluation of Hydrophobic Microcionamide‐Inspired Peptides

“…Following purification, the desired compounds 1 and 2 were obtained in 6.4 % and 6.6 % yield, respectively. To some extent, this was expected because low percent yields (<10 %) are usually reported in the synthesis of very hydrophobic peptides due to difficulties in synthesis and purification [14–17] . A significantly higher amount of compound 3 was obtained after purification, with a percent yield of 23.4 %.…”

“…To some extent, this was expected because low percent yields (< 10 %) are usually reported in the synthesis of very hydrophobic peptides due to difficulties in synthesis and purification. [14][15][16][17] A significantly higher amount of compound 3 was obtained after purification, with a percent yield of 23.4 %. From these results, it was evident that percent yields correlated negatively with the hydrophobicity of the peptides.…”

Natural Cyclopeptides as Anticancer Agents in the Last 20 Years

“…Differed from other congeners (reniochalistatins A-D) of the same origin, this compound showed in vitro cytotoxicity against RPMI-8226 (human myeloma) and MGC-803 (human gastric carcinoma) cells with IC 50 values of 4.9 and 9.7 µM, respectively [64]. The subsequent total synthesis of reniochalistatin E provided some inspiring methods for the synthetic strategies of cyclopeptides with similar structures [65].…”