Spiro ent-Clerodane Dimers: Discovery and Green Approaches for a Scalable Biomimetic Synthesis

Abstract

Scospirosins A (1) and B (2), two unprecedented spiro ent-clerodane dimers with 6/6/10/6 and 6/6/6/6/6 ring systems, respectively, were isolated from Isodon scoparius. Their structures were unambiguously established by spectroscopic, X-ray crystallographic, and chemical approaches. A bioinspired protecting-group-free strategy for their synthesis was achieved on a gram scale and featured the application of green methods, including neat reaction, sensitized photooxygenation, and electrochemical oxidation. 2 exhibited selective immunosuppressive activity against the proliferation of T lymphocytes (IC50 = 1.42 μM).