%0 Generic %A Xu, Chen %A Han, Arthur %A Virgil, Scott C. %A Reisman, Sarah E. %D 2017 %T Chemical Synthesis of (+)-Ryanodine and (+)-20-Deoxyspiganthine %U https://acs.figshare.com/articles/dataset/Chemical_Synthesis_of_-Ryanodine_and_-20-Deoxyspiganthine/4737463 %R 10.1021/acscentsci.6b00361.s003 %2 https://ndownloader.figshare.com/files/7735450 %K intracellular calcium ion channels %K synthesis %K strategy %K chemical %K Ryanodine %K pyrrole -2-carboxylate ester %K ryanodine receptors %X (+)-Ryanodine is a natural product modulator of ryanodine receptors, important intracellular calcium ion channels that play a critical role in signal transduction leading to muscle movement and synaptic transmission. Chemical derivatization of (+)-ryanodine has demonstrated that certain peripheral structural modifications can alter its pharmacology, and that the pyrrole-2-carboxylate ester is critical for high affinity binding to ryanodine receptors. However, the structural variation of available ryanodine analogues has been limited by the challenge of site-specific functionalization of semisynthetic intermediates, such as (+)-ryanodol. Here we report a synthetic strategy that provides access to (+)-ryanodine and the related natural product (+)-20-deoxyspiganthine in 18 and 19 steps, respectively. A key feature of this strategy is the reductive cyclization of an epoxide intermediate that possesses the critical pyrrole-2-carboxylate ester. This approach allows for the direct introduction of this ester in the final stage of the synthesis and provides a framework for the synthesis of previously inaccessible synthetic ryanoids. %I ACS Publications