The first total syntheses of aflavazole (6) and 14-hydroxyaflavinine (8), two sterically congested indole diterpenoids, were accomplished. AlI-promoted alkyne Prins cyclization was exploited to construct their key structural motifs. An electrocyclization-aromatization sequence assembled the pentasubstituted arene of 6, and a Stille-Migita coupling furnished the tetrasubstituted olefin of 8. The benzylic and allylic C-O bonds were reductively cleaved at the late stage of the syntheses, respectively.

Sesquiterpenoids are a group of naturally occurring 15-carbon isoprenoid compounds that are mainly found in higher plants, microorganism and marine life. Many of them provided encouraging leads for chemotherapeutics. In this review, the sesquiterpenoids are classified according to the ring numbering system and the functional groups presented in the core structures as acyclic, mono-, bi-, and tricyclic derivatives, and a current overview of sesquiterpenoids as potential cytotoxic anticancer agents is provided.

The architecturally symmetrical and synthetically challenging marine natural products lomaiviticins A and B present alluring synthetic targets due to their molecular complexity, potent antitumor properties, and natural scarcity. Herein, we report the total synthesis of the fully glycosylated monomeric unit of lomaiviticin A, monolomaiviticin A. The retrosynthetically derived synthetic strategy relied on an intramolecular palladium-catalyzed coupling reaction to complete the tetracyclic aglycon scaffold and gold-promoted glycosylations to install the synthetically challenging αand β-glycoside moieties of the target molecule. This accomplishment paves a path for the eventual total synthesis of lomaiviticins A and B and opens opportunities for biological investigations within this family of compounds.

Our previous studies with shishijimicin A resulted in the total synthesis of this scarce marine natural product and a number of its simpler analogues endowed with picomolar potencies against certain cancer cell lines. Herein, we describe the design, synthesis, and biological evaluation of four linker-drugs, anticipating the construction of antibody–drug conjugates (ADCs) as the ultimate goal of this research program. Using a common payload, the assembly of these linker-drugs utilized different linkers and attachment points, providing opportunities to probe the optimal molecular design of the intended ADCs as targeted cancer therapies. In the course of ADC generation and in vitro evaluation, we identified two linker-drugs with a promising in vitro plasma stability profile and excellent targeted cytotoxicity and specificity. Conjugation of shishijimicin A enediyne payloads through their phenolic moiety represents a novel approach to enediyne ADC creation, while the pharmacological profiles of at least two of the generated ADCs compare well with the profiles of the corresponding clinically approved ADC Kadcyla.