6688-49-9Relevant academic research and scientific papers
A 15-step synthesis of (+)-ryanodol
Chuang, Kangway V.,Xu, Chen,Reisman, Sarah E.
, p. 912 - 915 (2016)
(+)-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.
Asymmetric Total Synthesis of (+)-Ryanodol and (+)-Ryanodine
Masuda, Kengo,Koshimizu, Masaki,Nagatomo, Masanori,Inoue, Masayuki
, p. 230 - 236 (2016/01/25)
(+)-Ryanodine (1) is the ester derivative of 1H-pyrrole-2-carboxylic acid and the complex terpenoid (+)-ryanodol (2), which possesses eleven contiguous stereogenic centers on the ABCDE-ring system. Compound 1 is known to be a potent modulator of intracellular calcium release channels, whereas the activity of 2 is significantly weaker. To chemically construct 1, the multiple oxygen functional groups must be installed on the fused pentacycle in stereoselective fashions and the extremely hindered C3-hydroxy group must be acylated in a site-selective manner. First, the total synthesis of 2 was accomplished by introducing the five stereocenters from the previously prepared enantiopure ABDE-ring 7. Stereoselective construction of the C3-secondary, C2- and C6-tertiary alcohols was achieved by three nucleophilic reactions. The C9- and C10-trisubstituted carbon centers were regio- and stereoselectively introduced by hydroboration/oxidation of the six-membered C-ring, which was formed by the ring-closing metathesis reaction. Direct esterification of the C3-alcohol with pyrrole-2-carboxylic acid proved unsuccessful; therefore, we developed a new, two-step protocol for attachment of the pyrrole moiety. The C3-hydroxy group was first converted into the less sterically cumbersome glycine ester, which was then transformed into the pyrrole ring through condensation with 1,3-bis(dimethylamino)allylium tetrafluoroborate. This procedure resulted in the first total synthesis of 1.
The total synthesis of (+)-ryanodol. Part IV. Preparation of (+)-raynodol from (+)-anhydroryanodol
Deslongchamps, Pierre,Belanger, Andre,Berney, Daniel J. F.,Borschberg, Hans-Juerg,Brousseau, Robert,et al.
, p. 186 - 192 (2007/10/02)
This paper reports the transformation of (+)-anhydroryanodol (6) to (+)-ryanodol (7) by reductive cyclization of lactone epoxide derivatives 9 and 20 (Scheme 4).
