Access to a Structurally Complex Compound Collection via Ring Distortion of the Alkaloid Sinomenine

Many compound collections used in high-throughput screening are composed of members whose structural complexity is considerably lower than that of natural products. We previously reported a strategy for the synthesis of complex and diverse small molecules from natural products using ring-distortion reactions, called complexity-to-diversity (CtD), and herein, CtD is applied in the synthesis of 16 diverse scaffolds and 65 total compounds from the alkaloid natural product sinomenine. Chemoinformatic analysis shows that these compounds possess complex ring systems and marked three-dimensionality.