title: A 15-step synthesis of (+)-ryanodol.
abstract: (+)-Ryanodine and (+)-ryanodol are complex diterpenoids that modulate intracellular calcium-ion release at ryanodine receptors, ion channels critical for skeletal and cardiac muscle excitation-contraction coupling and synaptic transmission. Chemical derivatization of these diterpenoids has demonstrated that certain peripheral structural modifications can alter binding affinity and selectivity among ryanodine receptor isoforms. Here, we report a short chemical synthesis of (+)-ryanodol that proceeds in only 15 steps from the commercially available terpene (S)-pulegone. The efficiency of the synthesis derives from the use of a Pauson-Khand reaction to rapidly build the carbon framework and a SeO2-mediated oxidation to install three oxygen atoms in a single step. This work highlights how strategic C-O bond constructions can streamline the synthesis of polyhydroxylated terpenes by minimizing protecting group and redox adjustments.
authors: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors: Kangway V
authors: KV
authors: Chuang
authors: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors: Chen
authors: C
authors: Xu
authors: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA. reisman@caltech.edu.
authors: Sarah E
authors: SE
authors: Reisman
mesh_terms: D001688:Biological Products / Q000138:chemical synthesis*; D000081005:Cyclohexane Monoterpenes; D039821:Monoterpenes / Q000737:chemistry; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry; D012433:Ryanodine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D064588:Selenium Oxides / Q000737:chemistry
chemical_list: D001688:Biological Products; D000081005:Cyclohexane Monoterpenes; D039821:Monoterpenes; D019837:Ryanodine Receptor Calcium Release Channel; D064588:Selenium Oxides; C000608459:ryanodol; D012433:Ryanodine; C039648:pulegone; D010100:Oxygen