Synthetic Modulation of an Unstable Dehydrosecodine-type Intermediate and Its Encapsulation into a Confined Cavity Enable Its X-ray Crystallographic Observation.

Numerous indole alkaloids such as the iboga- and aspidosperma-type are believed to be biosynthesized via a common hypothetical intermediate, dehydrosecodine. The highly reactive nature of dehydrosecodine-type compounds has hampered their isolation and structural elucidation. In this study, we achieved the first X-ray structural determination of a dehydrosecodine-type compound by integrating synthetic optimization of the reactivity and stabilizing the fragile molecule by encapsulation into a supramolecular host.

Synthesis of a Halicyclamine-Type Macrocyclic Scaffold via Biomimetic Transannular Cyclization.

Previous attempts for biomimetic transannular reactions between two dihydropyrdine (DHP) rings incorporated in macrocycle frameworks relevant to manzamine alkaloids have been unsuccessful. Herein, we report an efficient regiocontrolled transannular cyclization of -symmetric macrocyclic precursor with rational modifications of the 3 and 6 positions of the DHP rings to synthesize a halicyclamine-type scaffold. The -double bonds installed in the macrocyclic alkyl loops played a crucial role in achieving the biomimetic transannular cyclization.

Regiocontrolled Dimerization of Densely Functionalized 1,6-Dihydropyridines for the Biomimetic Synthesis of a Halicyclamine-type Scaffold by Preventing Disproportionation.

The biomimetic dimerization of 1,6-dihydropyridines (DHPs) remains a daunting challenge due to competitive disproportionation pathways. Herein we report the regioselective dimerization of densely functionalized 1,6-DHPs that allow direct access to the bis-nitrogen bicyclic scaffold of halicyclamines. Disproportionation triggered by the hydride shift of 1,6-DHP was suppressed by the use of geminal disubstituted substrates.