Scalable Total Synthesis, IP3R Inhibitory Activity of Desmethylxestospongin B, and Effect on Mitochondrial Function and Cancer Cell Survival. (8th April 2021)

• Record Type: Journal Article
• Authors: Podunavac, Maša; Mailyan, Artur K.; Jackson, Jeffrey J.; Lovy, Alenka; Farias, Paula; Huerta, Hernan; Molgó, Jordi; Cardenas, Cesar; Zakarian, Armen
• Is Part Of: Angewandte Chemie. Volume 133:Number 20(2021)
• Page Start: 11378
• Page End: 11382
• Publication Date: 2021-04-08
• Subjects: cancer -- IP3R receptor -- metabolism -- total synthesis -- xestospongins; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202102259
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: The scalable synthesis of the oxaquinolizidine marine natural product desmethylxestospongin B is based on the early application of Ireland–Claisen rearrangement, macrolactamization, and a late‐stage installation of the oxaquinolizidine units by lactam reduction. The synthesis serves as the source of material to investigate calcium signaling and its effect on mitochondrial metabolism in various cell types, including cancer cells. Abstract : Desmethylxestospongin B (dmXe B) is a complex marine natural product that exhibits unique properties as a modulator of calcium signaling with downstream effects on cancer cell mitochondrial metabolism. We report a scalable total synthesis of dmXe B by a flexible synthetic strategy that allows for control of oxidation levels and stereochemistry at C9/9′.