Enantioselective Total Synthesis of (-)-Caldaphnidine O via a Radical Cyclization Cascade.

The synthetically challenging, diverse chemical skeletons and promising biological profiles of the alkaloids have generated intense interest from the synthetic chemistry community. Herein, the first and enantioselective total synthesis of (-)-caldaphnidine O, a complex bukittinggine-type alkaloid, is described. The key transformations in this concise approach included an intramolecular aza-Michael addition, a ring expansion reaction sequence, a Sm(II)/Fe(III)-mediated Kagan-Molander coupling, and the rapid formation of the entire hexacyclic ring skeleton of the target molecule via a radical cyclization cascade reaction, which was inspired by an unexpected radical detosylation observed in our recent dapholdhamine B synthesis.

Total Synthesis of Dapholdhamine B and Dapholdhamine B Lactone.

The intriguing structural complexity and bioactivities of the alkaloids have long attracted much attention. Herein, we report the first and enantioselective total synthesis of alkaloid dapholdhamine B and its lactone derivative. The chemical structure of dapholdhamine B contains a unique aza-adamantane core skeleton and eight contiguous stereocenters, including three contiguous fully substituted stereocenters, which present a formidable synthetic challenge.

Triptolide derivatives as potential multifunctional anti-Alzheimer agents: Synthesis and structure-activity relationship studies.

Owning to the promising neuroprotective profile and the ability to cross the blood-brain barrier, triptolide has attracted extensive attention. Although its limited solubility and toxicity have greatly hindered clinical translation, triptolide has nonetheless emerged as a promising candidate for structure-activity relationship studies for Alzheimer's disease. In the present study, a series of triptolide analogs were designed and synthesized, and their neuroprotective and anti-neuroinflammatory effects were then tested using a cell culture model.