Development of a biologically active secondary metabolite into a useful medicine requires continuous access to meaningful quantities of material. Although any chemical synthesis is broadly useful for its versatility, identification of a synthesis route that can be economically scaled represents a greater challenge. Here we report a concise synthesis of the neurotrophic trace metabolite (-)-jiadifenolide and its production on a gram-scale. The brevity of the route and the structural similarity of a key intermediate to many potent Illicium terpenes make chemical synthesis the unquestionable method for accessing and modifying these potential therapeutics.

7,20-Diisocyanoadociane, a scarce marine metabolite with potent antimalarial activity, was synthesized as a single enantiomer in 13 steps from simple building blocks (17 linear steps). Chemical synthesis enabled identification of ICT antiplasmodial activity against liver-stage parasites, which suggested heme detoxification does not exclusively underlie the mechanism of action of this class.

The vinylogous Mukaiyama aldol reaction (VMAR) allows efficient access to larger segments for complex natural product synthesis, primarily polyketides, through the construction of vicinal hydroxyl and methyl groups as well as di and tri-substituted double bonds in one single operation. In this review, we will highlight stereoselective protocols that have been used in natural product synthesis and cluster them into the four groups that can be obtained from different silyl ketene acetals or enol ethers. At the beginning, an overview on different stereoselective VMARs is presented; disregarding their applications in total syntheses.

[reaction: see text] Readily tunable and bifunctional L-prolinamides as novel organocatalysts have been developed, and their catalytic activities were evaluated in the direct asymmetric Aldol reactions of various aromatic aldehydes and cyclohexanone. High isolated yields (up to 94%), enantioselectivities (up to 99% ee), and anti-diastereoselectivities (up to 99:1) were obtained under the optimal conditions.