- Chemical conversion of ryanodol to ryanodine
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Ryanodine (1) is a plant-derived natural product with powerful pharmacological and insecticidal action, and is a potent modulator of intracellular calcium release channels. Compound 1 possesses a 1H-pyrrole-2-carboxylate ester at the C3-position of heptahydroxylated terpenoid ryanodol (2). Whereas 2 was readily obtained from 1 by basic hydrolysis, 1 has never been synthesized from 2, due to the extreme difficulty in selectively introducing the bulky pyrrole moiety at the severely hindered C3-hydroxyl group of heptaol 2. Here we report chemical conversion of 2 to 1 for the first time. The derivatization was realized through the use of a new protective group strategy and the application of on-site construction of the pyrrole-2-carboxylate ester from the glycine ester and 1,3-bis(dimethylamino)allylium tetrafluoroborate.
- Masuda, Kengo,Nagatomo, Masanori,Inoue, Masayuki
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p. 874 - 879
(2016/07/14)
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- Asymmetric Total Synthesis of (+)-Ryanodol and (+)-Ryanodine
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(+)-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.
- Masuda, Kengo,Koshimizu, Masaki,Nagatomo, Masanori,Inoue, Masayuki
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p. 230 - 236
(2016/01/25)
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- Investigation of the constituents of Ryania Speciosa
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Six new metabolites (2, 5-9) were isolated from the extracts of Ryania Speciosa Vahl.These compounds are closely related to ryanodine, the known insecticidal toxic alkaloid from this plant.
- Ruest, Luc,Taylor, David R.,Deslongchamps, Pierre
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p. 2840 - 2843
(2007/10/02)
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- Ryanoid Insecticides: Structural Examination by Fully Coupled Two-dimensional 1H-13C Shift Correlation Nuclear Magnetic Resonance Spectroscopy
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The two-dimensional pulse sequence, (?/2, 1H)-Δt1-(?/2, 1H; ?/2, 13C)-acquire, for 'fully coupled' 1H-13C shift correlation n.m.r. has been applied to structural analysis of ryanodine (1) and 9,21-didehydroryanodine (2) (a new botanical insecticide from Ryania speciosa).This procedure allowed total assignment of the 13C n.m.r. spectra using one-, two-, and three-bond 1H-13C couplings, stereochemical assignments of protons, and some conformational data via relative 3JCH couplings.The stucture (2) defined by n.m.r. was confirmed by reductive conversion into ryanodine (1) and 9-epi-ryanodine (3).
- Waterhouse, Andrew L.,Holden, Ian,Casida, John E.
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p. 1011 - 1016
(2007/10/02)
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- 9,21-Didehydroryanodine: a New Principal Toxic Constituent of the Botanical Insecticide Ryania
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A major insecticidal constituent of Ryania speciosa is isolated and characterized by n.m.r. and mass spectroscopy as the new alkaloid 9,21-didehydroryanodine (2); reduction of (2) with hydrogen (or tritium) gas yields both ryanodine (1) and 9-epiryanodine (3) (or their 9,21-3H analogues) in a 1 : 9 ratio.
- Waterhouse, Andrew L.,Holden, Ian,Casida, John E.
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p. 1265 - 1266
(2007/10/02)
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