The clerodane diterpene family possesses an impressive range of bioactivities and high synthetic challenge due to their unique amalgamation of rings, stereocenters, and oxygenation. Herein, we disclose the first total syntheses of three members, scaparvins B, C, and D, through a route fueled by several chemoselective and carefully orchestrated steps. One such operation is a tailored late-stage C-H functionalization converting a carboxylic acid into a lactone through the oxidation of a tertiary C-H bond under conditions that minimize epoxidation of an alkene. This step, among others, afforded critical functionality to complete the targets. In addition, use of an appropriate chiral catalyst with a Rawal diene renders the sequence enantioselective.

Although alkaloid natural products possess incredible diversity when considered broadly, certain domains are sometimes shared by several members, even from different sub-collections. Such homology can point to potential synthetic strategies. Herein, we highlight how such an analysis of the natural product arboridinine pinpointed two key elements of structural similarity that suggested the value of a metal-mediated 6-endo-dig cyclization to fashion its tetracyclic indolenine core, as well as the need to develop what could be considered a reversed polarity aza-Prins cyclization to deliver its tertiary allylic alcohol and final cage structure. The power of the latter design element is highlighted by several failures in achieving similar functional group patterning through more traditional aza-Prins and Mannich cyclization strategies. Overall, these operations fueled an inaugural 13-step racemic synthesis of the target; exploration of varied solutions for the enantioselective preparation of a key 7-membered indole-containing piece afforded a 16-step formal asymmetric solution.

Pre-schisanartanin C belongs to the family of Schisandra nortriterpenoids with potent antihepatitis, antitumor, and anti-HIV activities. This paper presents the enantioselective total synthesis of pre-schisanartanin C (1). An important step in the total synthesis of 1 is gold-catalyzed intramolecular cyclopropanation of a 1,8-enyne substrate bearing a secondary ester group at the propargylic position to prepare a bicyclo[6.1.0]­nonane core. Additional highlights include (i) an asymmetric Diels–Alder reaction to install the initial C5 stereogenic center of 1 and (ii) a sequential Pd-catalyzed Stille coupling, regio- and stereoselective Sharpless asymmetric dihydroxylation, and a subsequent intramolecular lactonization to construct the side chain of 1. The developed chemistry paves the way for the total syntheses of other family members bearing highly rigid bicyclo[6.1.0]­nonane cores.