[Studies of the total synthesis of (-)-ranunculin].
The synthesis of (-)-ranunculin from mannitol is described. The oxidation of 1,2,5,6-diacetone d-mannitol with NaIO4 or lead tetraacetate gave 2,3-O-isopropylidene-D-glyceraldehyde with the desired alpha-carbon-(R)-configuration. The Wittig reaction of isopropylidene-D-glyceraldehyde with (C6H5)3P = CHCOOCH3 gave a mixture of Z and E methyl-3-(2,2-dimethyl-1,3-dioxo-lan-4-yl)-2-propenoate with a Z:E ratio of 85:15. The dependence of Z:E ratio upon the solvent present was studied. On careful treatment of the cis isomer with 0.1 mol/L HCl, hydrolysis of the ketal took place along with cyclization to give the optically active aglycone with the expected stereochemistry, which was followed by Koenigs-Knorr reaction to give (-)-ranunculin tetraacetate. Since the glycoside is sensitive to acid and base, hydrolysis was carried out with strongly acidic cation exchange resin which yielded (-)-ranunuculin smoothly. The overall yield from mannitol with all the intermediates purified amounted to 15%.
Fang
Z
Z
Zhou
J
J
Huang
L
L
D005663:Furans / Q000138:chemical synthesis* / Q000494:pharmacology; D008759:Methylglycosides / Q000138:chemical synthesis* / Q000494:pharmacology
D005663:Furans; D008759:Methylglycosides; C039859:ranunculin