Total Synthesis Of5,6-Secoarguterin And Nitidine

The iridoids are large class of naturally occurring compounds with over900membersin the family. They represent a highly oxygenated monoterpenoid skeleton characterised bya functionalised cyclopentane ring cis-fused to a dihydropyran, δ-1actol or δ-1actone. Theearly examples of these cyclopentanoid monoterpenes, iridomyrmecin1andisoiridomyrmecin2，were isolated almost nine decades ago and have attracted considerableattention because of their diverse biological action and interesting structure.Our group has isolated many new natural products from Incarvilea arguta, includingcarbolines, terpenoids and iridoid lactones.5,6-secoarguterin was indetified as a newiridoid skeleton.Previous secoarguterin reported is7,8-secoarguterin. This5,6-secoarguterin isolated issignificant for natural product classification. This structure is composed of two six-memberring and three achiral centers. It is simple but not easy to synthesis.We tried to build this molecular by many methods, but only one succeeded. The keyintermediate was constructed by H-D-A reaction, while three asymmetric centers were setup. The target molecular was synthesized after13steps. The total yield was0.73%and thetarget molecular was identified by1H NMR,13C NMR, ESI, NOE. The absolute structurewas confirmed using X-ray crystallography. The data of synthetic compound wasconfirmed by the original data.Nitidine chloride (Zanthoxylum nitidum) has many names in China. It is a kind oftraditional Chinese medicine. It is recorded by ‘ben cao gang mu’ and Chinese medicinaldicnary (1955). The leaves，stem and roots can be used as medicine to release many pains.A series of strategies have been developed for the synthesis of Nitidine chloride andits derivations which exhibits various biological activities. Our group found that nitidinechloride is positive for IL-10. Nitidine chloride is expensive. This disadvantage drove us tofind a more economic approach to nitidine chloride. The process of nitidine was optimized. A reasonable process was schuelded. The key intermediate was constructed by inter-Heckreation, followed by methylated, icon exchanged. The total yield was25.5%.