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

Abstract

Ever 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 yuzuriminetype 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.

The Total Synthesis of Diquinane‐Containing Natural Products

“…Although a lot of achievements have been made on total synthesis of diquinane‐containing natural products, an enormous knowledge gap there still remains for future research on this subject. For instance, it deserves more breakthroughs in the following two aspects 1) development of more new strategies for those “unconquered land and missing links” among diquinane‐containing Daphniphyllum alkaloids discovered; [82] 2) utilization of those readily available diquinane building blocks in total synthesis of complex natural products accompanied with a variety of novel, more efficient, and sustainable chemical reactions, such as ring size‐modulation, C−C bond cleavage, C−H activation and skeletal rearrangements, as well as, in particular, under the photocatalysis and/or organocatalysis paradigms. Along with the elucidation of novel structures and on‐going unparalleled bioactivity studies in the terpenoid‐centered phytochemical research, the ever‐growing number of compounds bearing a diquinane unit will definitely continue to give further movement to the field of natural product total synthesis in the years to come.…”

Integrative metabolomics reveal the organisation of alkaloid biosynthesis in Daphniphyllum macropodum

“…Based on their skeletal structures, they can be categorised into 13−35 structurally distinct type subclasses including daphniphylline, secodaphniphylline, calyciphylline-A, yuzurimine, and yuzurine types (9). Due to their structural complexity and potential biological activities, Daphniphyllum alkaloids (DAs) have remained targets for total synthesis efforts over many decades (10)(11)(12)(13)(14)(15).…”

Studies toward the Total Syntheses of Calyciphylline D-Type Daphniphyllum Alkaloids

“…Heathcock and co-workers had accomplished six alkaloids including (±)-methyl homodaphniphyllate, methyl homosecodaphniphylline, daphnilactone A, ,,, secodaphniphylline, bukittinggine, and codaphniphylline via elegant biomimetic total syntheses. Recently, the groups of Carreira, Li, Smith, Fukuyama, Hanessian, Dixon, Zhai, Xu, Gao, Sarpong, Qiu, and Li have reported total syntheses of several other types of Daphniphyllum alkaloids.…”