Cannagenol and cannogenol-3-O-alpha-L-rhamnoside are natural cardiotonic steroids isolated from <i>convallaria majalis</i>. They have been shown to possess various modes of biological activities and hence represent attractive targets.  Current synthesis on the motifs of this class of steroid involves semi synthesis which will require intensive effort if some modification in the molecule is desired. This limits the structural diversity of the small molecules towards biological evaluation.<br/>Here, we report the first enantioselective total synthesis of cannogenol and cannogenol-3-O-alpha-L-rhamnoside. Our approach features enantioselective Cu(II)box promoted Michael reaction, tandem aldol cyclization reactions, and one pot reduction/transposition to synthesize an intermediate that allows accessibility to several natural products in this family and their derivatives. Once the steroid core is assembled, the butanolide moiety is installed following known protocol to complete the synthesis of cannogenol. Cannogenol, thus synthesized, was selectively acetylated at C-19 and glycosylated at C-3 with rhamnoside to give cannogenol-3-O-alpha-L-rhamnoside after global deprotection. The rapid assembly of functionalized intermediate allows for the concise and scalable synthesis of these two natural products.

Enantioselective total synthesis of cannogenol and cannogenol-3-O-alpha-L-rhamnoside

254th National Meeting (2017)

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