10.1021/ja0401702
The study presents the first total syntheses of the monoterpene alkaloids (-)-incarvilline, (+)-incarvine C, and (-)-incarvillateine, which are natural compounds with potent analgesic activity. The synthesis strategy utilized 6-epi-incarvilline as a common precursor, constructed through a three-component coupling reaction and a reductive Heck-type reaction to form the cyclopentanone and perhydro-2-pyrindine skeletons, respectively. Additionally, the study investigated the topochemically controlled [2 + 2] photodimerization of cinnamic acid derivatives to construct the 1,2,3,4-tetrasubstituted cyclobutane ring specific to (-)-incarvillateine. Various chemicals were employed, including (4S)-4-siloxy-2-cyclopenten-1-one, organozinc reagents, iodomethane, N-Boc-tosyl amide, and palladium catalysts, among others, to achieve the desired synthetic transformations and construct the complex molecular frameworks of the target alkaloids. These chemicals served the purpose of facilitating specific reactions and transformations necessary to synthesize the target compounds, ultimately allowing for the establishment of their structures and absolute configurations.
