Total Synthesis of Apoptolidin: Completion of the Synthesis and Analogue Synthesis and Evaluation
journal contributionposted on 17.12.2003, 00:00 authored by K. C. Nicolaou, Yiwei Li, Kazuyuki Sugita, Holger Monenschein, Prasuna Guntupalli, Helen J. Mitchell, Konstantina C. Fylaktakidou, Dionisios Vourloumis, Paraskevi Giannakakou, Aurora O'Brate
The total synthesis of apoptolidin (1) is reported together with the design, synthesis, and biological evaluation of a number of analogues. The assembly of key fragments 6 and 7 to vinyl iodide 3 via dithiane coupling technology was supplemented by a second generation route to this advanced intermediate involving a Horner−Wadsworth−Emmons coupling of fragments 22 and 25. The final stages of the synthesis featured a Stille coupling between vinyl iodide 3 and vinylstannane 2, a Yamaguchi lactonization, a number of glycosidations, and final deprotection. The developed synthetic technology was applied to the construction of several analogues including 74, 75, and 77 which exhibit significant bioactivity against tumor cells.