A 15-step synthesis of (+)-ryanodol

(+)-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 demonstra...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2016-08, Vol.353 (6302), p.912-915
Main Authors: Chuang, Kangway V., Xu, Chen, Reisman, Sarah E.
Format: Article
Language:English
Subjects:
Biochemistry
Biological Products - chemical synthesis
Calcium
Carbon
Chemical bonds
Chemical synthesis
Chemistry
Construction
Monoterpenes - chemistry
Oxidation
Oxidation-Reduction
Oxygen
Oxygen - chemistry
Receptors
Ryanodine - analogs & derivatives
Ryanodine - chemical synthesis
Ryanodine Receptor Calcium Release Channel - metabolism
Selenium Oxides - chemistry
Synthesis
Synthesis (chemistry)
Terpenes
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Description
Summary:(+)-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-0 bond constructions can streamline the synthesis of polyhydroxylated terpenes by minimizing protecting group and redox adjustments.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.aag1028