biostudies-literatureXu CNational Institute of General Medical SciencesNIGMS NIH HHSEli Lilly and CompanyNovartis278-282https://www.ebi.ac.uk/biostudies/studies/S-EPMC5409222biostudies-literatureUnknown3(4)(+)-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, respeACS central scienceChemical Synthesis of (+)-Ryanodine and (+)-20-Deoxyspiganthine.PMC5409222RGM097582-01R35 GM118191-01R35 GM118191R01 GM097582T32 GM007616Han AReisman SEXu CVirgil SCfalseChemical Synthesis of (+)-Ryanodine and (+)-20-Deoxyspiganthine.(+)-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, respe2017-01-01T00:00:00Z2017 Apr2025-04-05T15:14:02.888Z2019-03-27T02:42:17ZS-EPMC54092222847004410.1021/acscentsci.6b00361