Asymmetric total synthesis of yuzurimine-type Daphniphyllum alkaloid (+)-caldaphnidine J

• DOI: 10.1038/s41467-020-17350-x
• Publication Date: 2020-07-15T10:04:02Z
• Authors: Lian-Dong Guo; Yan Zhang; Jingping Hu; Chengqing Ning; Heyifei Fu; Yuye Chen; Jing Xu
• Keywords: Biological Products; Samarium; Magnetic Resonance Spectroscopy; Molecular Structure; Science; Q; Stereoisomerism; Ethylenes; Ketones; 01 natural sciences; Article; Catalysis; 0104 chemical sciences; Daphniphyllum; Oxygen; Alkaloids; Models, Chemical; Drug Design; Oxidation-Reduction

AbstractEver since Hirata’s report of yuzurimine in 1966, nearly fifty yuzurimine-type alkaloids have been isolated, which formed the largest subfamily of the Daphniphyllum alkaloids. Despite extensive synthetic studies towards this synthetically challenging and biologically intriguing family, no total synthesis of any yuzurimine-type alkaloids has been achieved to date. Here, the first enantioselective total synthesis of (+)-caldaphnidine J, a highly complex yuzurimine-type Daphniphyllum alkaloid, is described. Key transformations of this approach include a highly regioselective Pd-catalyzed hydroformylation, a samarium(II)-mediated pinacol coupling, and a one-pot Swern oxidation/ketene dithioacetal Prins reaction. Our approach paves the way for the synthesis of other yuzurimine-type alkaloids and related natural products.