The Asymmetric Total Synthesis of (+)-Cytotrienin A, an Ansamycin-Type Anticancer Drug

✍ Scribed by Yujiro Hayashi; Mitsuru Shoji; Hayato Ishikawa; Junichiro Yamaguchi; Tomohiro Tamura; Hiroki Imai; Yosuke Nishigaya; Kenichi Takabe; Hideaki Kakeya; Hiroyuki Osada

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 370 KB
• Volume: 120
• Category: Article
• ISSN: 0044-8249
• DOI: 10.1002/ange.200802079

✦ Synopsis

Cytotrienin A (1) is a microbial antitumor secondary metabolite that was isolated from the fermentation broth of Streptomyces sp. RK95-74 from soil. [1] It possesses an E,E,E-triene motif within a 21-membered cyclic lactam, which also contains four chiral centers. These are common structural features of the ansamycin class of natural products, which include the mycotrienins (or ansatrienins), [2] trienomycins, [2c, 3] thiazinotrienomycins, [4] and trierixin. [5] Cytotrienin A, with its unusual aminocyclopropane carboxylic acid side chain, exhibits potent apoptosis-inducing activity on HL-60 cells with an ED 50 value of 7.7 nm. To facilitate elucidation of its mechanism of action, the development of a method for the total synthesis and derivatization of cytotrienin A is highly desirable.