An Expedient Total Synthesis of Chivosazole F: an Actin‐Binding Antimitotic Macrolide from the Myxobacterium Sorangium Cellulosum. Issue 2 (29th November 2016)

• Record Type: Journal Article
• Authors: Williams, Simon; Jin, Jialu; Kan, S. B. Jennifer; Li, Mungyuen; Gibson, Lisa J.; Paterson, Ian
• Is Part Of: Angewandte Chemie international edition. Volume 56:Issue 2(2017)
• Page Start: 645
• Page End: 649
• Publication Date: 2016-11-29
• Subjects: macrocycles -- macrolides -- polyenes -- Stille cross-coupling -- total synthesis; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201610636
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: A unified strategy for the chemical synthesis of the chivosazoles is described. This strategy is based on two closely related approaches involving the late‐stage installation of the isomerization‐prone (2 Z, 4 E, 6 Z, 8 E )‐tetraenoate motif, and an expedient fragment‐assembly procedure. The result is a highly convergent total synthesis of chivosazole F through the orchestration of three mild Pd/Cu‐mediated Stille cross‐coupling reactions, including the use of a one‐pot, site‐selective, three‐component process, in combination with controlled installation of the requisite alkene geometry. Abstract : Stille crazy after all these years : Total synthesis of the myxobacterial metabolite chivosazole F, a potent actin‐binding anticancer agent, has been achieved. The modular strategy explores two related approaches involving the careful orchestration of mild Pd/Cu‐mediated Stille cross‐coupling reactions in concert with achieving control over the geometry of the sensitive polyene arrays.