Syntheses of Glycyrrhetic Acid α-Diglycosides and Enol α-Glycosides

Glycyrrhetinate α-monoglycoside derivatives 8, 10 and 12, all having a trichloroacetyl group at the C-2 position of the pyranose ring, were treated with NH3-saturated ether at 0°C to give the corresponding alcohols 13, 15 and 17, accompanied by 2'-chloroderivatives, 14, 16 and 18, respectively. Glycosylations of the alcohols 13, 15 and 17 with methyl 2, 3, 4-tri-O-acetyl-α-D-glucuronatopyranosyl bromide 19 in the presence of AgOTf in dry CH2Cl2 gave the corresponding α-diglycosides 20, 22 and 24 together with the enol α-glycosides 21, 23 and 25, respectively. Glycosylations of the diglycoside derivatives 20, 22 and 35 having no reactive OH group in the molecules with 19 for longer reaction times gave quantitatively the enol α-glycoside derivatives 21, 23 and 36, respectively. Glycosylation of the monoglycoside derivative 37, which has a poorly reactive OH group at the C-4 position on the pyranose ring, with 19 gave an enol α-glycoside 38. The mechanism of the formation of enol α-glycosides was investigated. Removal of the protecting groups of 20, 22 and 24 by successive treatment with 1.5N NaOMe in MeOH and 5% KOH in EtOH-H2O (1 : 1) gave the free α-diglycosides 26-28, and removal of those of 31, 21, 23, 25 and 36 by treatment with 5% KOH in EtOH-H2O (1 : 1) under reflux gave the free enol α-glycosides 41-45, respectively.