Ten-Gram-Scale Total Synthesis of the Anticancer Drug Candidate E7130 to Supply Clinical Trials
Yosuke Kaburagi, Kazunobu Kira, Kenzo Yahata, Kentaro Iso, Yuki Sato, Fumiyoshi Matsuura, Isao Ōhashi, Yasunobu Matsumoto, Minetaka Isomura, Takeo Sasaki, Takashi Fukuyama, Yusuke Miyashita, Hiroshi Azuma, Daisuke Iida, Tasuku Ishida, W. Itano, Masaaki Matsuda, Masayuki Matsukura, Norio Murai, Satoshi Nagao, Masashi Seki, Akihiko Yamamoto, Yuji Yamamoto, Naoki Yoneda, Yuzo Watanabe, Atsushi Kamada, Akio Kayano, Katsuya Tagami, Osamu Asano, Takashi Owa, Yoshito Kishi
Abstract
E7130 is a novel drug candidate with an exceedingly complex chemical structure of the halichondrin class, discovered by a total synthesis approach through joint research between the Kishi group at Harvard University and Eisai. Only 18 months after completion of the initial milligram-scale synthesis, ten-gram-scale synthesis of E7130 was achieved, providing the first good manufacturing practice (GMP) batch to supply clinical trials. This paper highlights the challenges in developing ten-gram-scale synthesis from the milligram-scale synthesis.