Construction of the hasubanan alkaloid core through an oxidative dearomatization/lewis acid catalyzed cyclization

Abstract

Access to novel opioid receptor binding ligands is important as chronic pain continues to be a pervasive problem in healthcare. The hasubanan (HB) alkaloids have been identified as potential candidates for selective opioid receptor binding. These alkaloids are a family of compounds, primarily isolated from the flowering plants of the sp Stephania, which have been used for centuries in traditional medicinal remedies. While morphine and HB alkaloids share several structural features, the natural occurring HB alkaloids have a configuration opposite to that of morphine. The unnatural antipodes of the HB alkaloids have a similar spatial orientation to morphine, making then increasingly attractive as potential analgesic therapeutics. Based on these observations we were inspired to develop a synthetic strategy that allows access to both the natural and unnatural enantiomers for several of the HB alkaloid family members.