Total synthesis of ryanodol.
Ryanodol (1) exists in nature in the form of the 1H-pyrrole-2-carboxylate ester derivative known as ryanodine, which is a potent modulator of the calcium release channel. The pentacyclic ABCDE-ring system of 1 is fabricated with eight oxy groups, three methyl groups, and one isopropyl group. All the eight tetrasubstituted stereocenters are concentrated within the 10-carbon ABDE framework. The total synthesis of this exceptionally complex molecule was achieved in 22 steps from the simple C2-symmetric tricycle 8. The synthetic route is based on installation of the seven stereogenic centers and formation of the four C-C bonds within the highly congested multicyclic format. The novel and flexible strategy developed here will enable the generation of chemical derivatives with different functional properties toward calcium release channels.
Graduate School of Pharmaceutical Sciences, The University of Tokyo , Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Masanori
M
Nagatomo
Masaki
M
Koshimizu
Kengo
K
Masuda
Toshiki
T
Tabuchi
Daisuke
D
Urabe
Masayuki
M
Inoue
D015220:Calcium Channels / Q000378:metabolism; D060326:Chemistry Techniques, Synthetic; D010084:Oxidation-Reduction; D012433:Ryanodine / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology
D015220:Calcium Channels; D012433:Ryanodine