Total Synthesis of Dixiamycins A and B via a Late-Stage N-N Bond Formation under Visible Light Photoredox Catalysis.

Intermolecular oxidative N-N bond formation reactions are quite challenging and are largely uncharted. N-N linked dimeric indolosesquiterpene alkaloids represent an underexplored class of natural products, and strategies for direct dehydrogenative N-N bond formation are limited. Here, we have reported that a late-stage visible-light photoredox catalysis facilitates N-N bond formation, leading to the total syntheses of atropo-diastereomers dixiamycins A () and B ().

Biomimetic total synthesis of the reported structure of (+)-selaginedorffone B.

The first enantioselective total synthesis of the reported structure of the structurally unique aromatic tetraterpenoid of anti-cancer potential, (+)-selaginedorffone B (2), has been accomplished from two modified abietane diterpenoids through an intermolecular Diels-Alder reaction between a bio-inspired diene 3 (HOMO counterpart) and dienophile 4 (corresponding LUMO counterpart) in a 23-step sequence, whereas the core framework of the monomeric abietane diterpenoid was constructed alkyne-activated ene-cyclization. Computational analysis was conducted to reveal the intricate regio and diastereoselectivity of this novel Diels-Alder reaction, strengthening the experimental results. The absolute configuration of the synthesized molecule was validated through X-ray studies of late-stage intermediates as well as comprehensive 2D NMR analysis.

Total synthesis of (+)-oridamycins A and B.

We have accomplished a unified strategy to achieve the structurally intriguing indolosesquiterpene alkaloids with diverse biological activity, xiamycin A (1a), xiamycin A methyl ester (1b) and oridamycins A (2a), and B (2b), which possesses a complex 6/6/6/5/6-fused pentacyclic skeleton bearing a carbazole moiety fused with a highly functionalized -decalin motif. Lewis acid-mediated epoxy-ene cyclization establishes the required pentacyclic scaffold with the installation of the four contiguous stereogenic centers. Further oxidative cleavage of the vinyl functionality, followed by successive functional group interconversions, completed the total synthesis of the indolosesquiterpene alkaloids.

Highly chemoselective oxidative dimerization of indolosesquiterpene alkaloids: a biomimetic approach to dixiamycin.

Dimeric indolosesquiterpene alkaloids, typically N-N- and C-N-linked xiamycin dimers, feature a pentacyclic framework with four contiguous stereogenic centers at the periphery of a -decalin scaffold to which a carbazole unit is attached. In comparison with actual biosynthetic dixiamycin derivatives, we designed C-C-linked xiamycin dimers, aiming to use them as a powerful tool to create unique scaffolds as drug candidates. In this work, we disclose the first synthetic route to access a C-C dimeric indolosesquiterpene skeleton, featuring a hypervalent iodine (PIFA)-catalyzed oxidative dimerization reaction in a single-step operation with overwhelming control over the chemoselectivity and regioselectivity.

Total synthesis of atropisomeric indolosesquiterpenoids N-N bond formation: dixiamycins A and B.

N-N dimeric indolosesquiterpene alkaloids constitute a class of under-investigated architecturally intriguing natural products. Herein, we report the first chemical oxidation approach to the asymmetric total syntheses of these atropisomeric indolosesquiterpenoids through N-N bond formation. Specifically, dixiamycins A (1a) and B (1b) were prepared through a Cu(i)-mediated aerobic dehydrogenative dimerization from the naturally occurring monomer xiamycin A methyl ester (2b); this preparation also represents the first total synthesis of dixiamycin A (1a).