Biomimetic Total Synthesis of Dysoxylum Alkaloids.

A five-step total synthesis of Dysoxylum alkaloids has been achieved using a biomimetic approach from zanthoxylamide protoalkaloids. The synthesis featured a direct amidation and a Bischler-Napieralski reaction to form the dihydroisoquinoline ring, which was then subjected to a Noyori asymmetric transfer hydrogenation to establishing the stereogenic center at C-1. Our synthetic sequence provides an important perspective on the biosynthetic origin of Dysoxylum alkaloids, since six natural alkaloids and twelve synthetic analogues were obtained with high enantioselectivity and in overall yields up to 68 %. In addition, we describe the acute toxicity toward zebrafish embryos of Dysoxylum alkaloids, comparing their toxicity with their corresponding zanthoxylamide protoalkaloids and establishing an enantioselectivity-toxicity relationship.