Novel Synthetic Approaches into Intensely Sweet Glycosides: Baiyunoside and Osladin

Novel synthetic approaches into intensely sweet glycosides, baiyunoside and osladin, have been developed. Baiyunoside, a diterpene glycoside isolated from Chinese drug Bai-Yun-Shen, is 250 times sweeter than sucrose. The aglycone of baiyunoside, baiyunol, have been synthesized as racemate by means of the biomimetic olefin cyclization induced by mercury(II) triflate. Introduction of sugar residue afforded natural baiyunoside and stereoisomers or analogs with other sugar residues. One analog was sweeter than natural product, while some were very bitter. Well-known saponin osladin is the sweet principle of a fern, Polypodium vulgare (Polypodiaceae). Although we accomplished the total synthesis of the saponin corresponding to the reported structure for osladin, it was not sweet at all. Reextraction of the rhizomal sweet principle of the fern and a single crystal X-ray diffraction study revealed its real structure to be isomeric 26-O-α-L-rhamnopyranosyl-(22R,25S,26R)-22,26-epoxy-6-oxo-5α-cholestan-3β,26-diol-3-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranoside. The synthesis of the real osladin was achieved by using a newly developed β-selective and 2’ hydroxyl group discriminating glucosylation procedure and an α-selective thermal rhamnosylation reaction. Synthetic osladin was very sweet, thus showing that osladin is proved to be the real sweet principle of the fern.

Sweet Taste - Glycoside - Baiyunoside - Osladin - Synthesis - Polypodoside A - Structure Revision