Synthesis of an Iridoid-Inspired Compound Collection and Discovery of Autophagy Inhibitors

Iridoids comprise a large group of monoterpenoid natural products displaying a diverse array of biological activities ranging from neurotrophic to anti-inflammatory and anti-tumorigenic properties. Therefore, the development of concise synthesis routes to compound collections inspired by the structural features of these natural products is of particular relevance for chemical biology and medicinal chemistry. Herein we describe a samarium diiodide-mediated synthesis of a small, focused iridoid-inspired compound collection. Characterization of these iridoid analogues in biological assays revealed novel small-molecule inhibitors of autophagy.