Total Synthesis of (-)- and (+)-Talaroenamine B and Diphenylene Derivatives.

Abstract

The first total synthesis of (±)-talaroenamine B was achieved through a concise four-step procedure. The key feature of this synthetic strategy lies in a one-pot reaction involving I (III)-mediated oxidative dearomatization to construct a racemic cyclohexanedione unit, followed by imination using a chiral auxiliary to afford a separable mixture of diastereoisomers. A further acid-catalyzed substitution reaction of aniline with the diastereoisomers led to the natural product (-)-talaroenamine B and its enantiomer (+)-talaroenamine B. Additionally, virtual screening was utilized to expand the chemo-diversity of talaroenamines, and (±)-talaroenamine B diphenylene derivatives 6-11 were obtained by replacing aniline with selected aniline derivatives in the final step of synthesis. The structures of the synthetic compounds were elucidated using NMR, HRESIMS, and electronic circular dichroism (ECD) data. Compound 6b displayed an acetylcholinesterase (AChE) inhibitory effect with an IC₅₀ value of 4.5 μM, as well as cytotoxicity against the K562 cell line with an IC₅₀ value of 5.6 μM.