253128-15-3Relevant articles and documents
Commercial manufacture of halaven: Chemoselective transformations en route to structurally complex macrocyclic ketones
Austad, Brian C.,Calkins, Trevor L.,Chase, Charles E.,Fang, Francis G.,Horstmann, Thomas E.,Hu, Yongbo,Lewis, Bryan M.,Niu, Xiang,Noland, Thomas A.,Orr, John D.,Schnaderbeck, Matthew J.,Zhang, Huiming,Asakawa, Naoki,Asai, Naoki,Chiba, Hiroyuki,Hasebe, Takashi,Hoshino, Yorihisa,Ishizuka, Hiroyuki,Kajima, Takashi,Kayano, Akio,Komatsu, Yuki,Kubota, Manabu,Kuroda, Hirofumi,Miyazawa, Mamoru,Tagami, Katsuya,Watanabe, Tomohiro
, p. 333 - 337 (2013)
The evolution of the synthesis of Halaven (E7389, INN eribulin mesylate) from a medicinal chemistry process to the execution of the final process on pilot scale is described. The completion of the synthesis of Halaven from C1-C13 ester and C14-C35 sulfone alcohol involves a series of chemo-, regio-, and stereoselective transformations. Furthermore, a high-dilution macrocyclization presented a number of challenges for industrial-scale manufacture (throughput, processing time, and side reactions). This paper describes studies at Eisai leading to an understanding, optimization, and control of the chemistry that realized the reproducible commercial production of Halaven.
METHODS USEFUL IN THE SYNTHESIS OF HALICHONDRIN B ANALOGS
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Paragraph 0078; 0079, (2015/06/17)
In general, the present invention features improved methods useful for the synthesis of analogs of halichondrin B, such as eribulin and pharmaceutically acceptable salts thereof (e.g., eribulin mesylate).
Macrocyclic ketone analogues of halichondrin B
Zheng, Wanjun,Seletsky, Boris M.,Palme, Monica H.,Lydon, Paul J.,Singer, Lori A.,Chase, Charles E.,Lemelin, Charles A.,Shen, Yongchun,Davis, Heather,Tremblay, Lynda,Towle, Murray J.,Salvato, Kathleen A.,Wels, Bruce F.,Aalfs, Kimberley K.,Kishi, Yoshito,Littlefield, Bruce A.,Yu, Melvin J.
, p. 5551 - 5554 (2007/10/03)
Synthesis and SAR studies of structurally simplified analogues of marine natural product halichondrin B resulted in the discovery of E7389, a new potential antitumor agent currently undergoing Phase I clinical trials. Structurally simplified macrocyclic ketone analogues of halichondrin B were prepared by total synthesis and found to retain the potent cell growth inhibitory activity in vitro, stability in mouse serum, and in vivo efficacy of the natural product.