1) Institute of Organic Chemistry, Ufa Scientific Center, Russian Academy of Sciences, 450054, Ufa, pr. Oktyabrya,
71, e-mail: email@example.com; 2) N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Division, Russian Academy
of Sciences. Translated from Khimiya Prirodnykh Soedinenii, No. 6, pp. 575-578, November-December, 2006. Original article
submitted November 24, 2005.
2006 Springer Science+Business Media, Inc.
Chemistry of Natural Compounds, Vol. 42, No. 6, 2006
SYNTHESIS OF METHYL ESTERS OF BETULINIC ACID
-GLYCOSIDES AND 28-OXO-19,28-EPOXYOLEANANE
O. B. Flekhter,
N. I. Medvedeva,
E. V. Tret
F. Z. Galin,
and G. A. Tolstikov
New 2-deoxy- and 2,6-dideoxy-α-L-arabinohexopyranosides of betulinic acid and 28-oxoallobetulin methyl
esters were synthesized by the glycal method.
triterpenoids, betulinic acid, glycosylation, glycals, glycosides.
The synthesis of glycosides of triterpene alcohols is interesting because of their valuable biological activity. Addition
of a sugar unit to the triterpene increases its water solubility, which is especially important in developing medicinal preparations.
Natural and synthetic glycosides of the lupane triterpene betulin (mainly
-glycosides have been reported) exhibited various
types of pharmacological activity. Thus, fruticesaponin B, which was isolated from Bupleurum fruticescens extract, exhibited
high activity toward inflammations caused by carrageenin, tetradecanoylphorbol acetate, arachidonic acid, and
Glycosides of betulin administered in lecithin liposomes can increase the effect of liposomal preparations for decreasing
the blood level of cholesterol in experimental hypercholesterolemia . The O-, S-, and N-glycosides of betulinic acid have been
patented for inhibition of lipoxygenase and intercellular adhesion . 3-O-Glucopyranosyl betulinic acid possess high growth-
regulating activity for the main root of cucumber (Cucumis sativus L., variety KIT) sprouts . Glycosides of betulin and its
monoacetates and 18,19-isobetulin were synthesized under Koenigs—Knorr and Helferich reaction conditions and had low
stereoselectivity and yields [5-7].
It seemed interesting to synthesize new
-glycosides, in particular, of betulinic acid and 28-oxoallobetulin, during a
study of their structure—activity relationships and ways to increase their solubility. We note that 28-oxoallobetulin exhibited
distinct anti-flu activity . However, this compound is practically insoluble in water, which has a detrimental effect on the
ability to study it further. Furthermore, glycosides of 28-oxoallobetulin have not been reported.
Triterpene glycosides were synthesized by the glycal method . The glycosyl donors were acetates of L-glucal (
); the activators, cation exchanger KU-2-8 (H
-form) and LiBr. This glycosylation method was successfully used
previously for preparation of glycyrrhetic acid and betulin 2-deoxy-
-glycosides [10, 11]. The glycosylation of the methyl ester
of betulinic acid (
) and 28-oxoallobetulin (
proceeded stereoselectively to form 2-deoxy- (
) in 83-88% yields (Scheme 1). The
-anomers were detected by TLC and NMR.
by KOH (5%) in CH
OH gave the target 2-deoxy-
-L-arabino- and 2,6-dideoxy-
in 80-87% yields.
The structures of the synthesized compounds (
) were established using NMR spectra and were compared with
literature data for the aglycon  and the carbohydrate part .
C NMR spectra of the aglycons of the glycosides were
analogous to the spectrum of the starting material with the exception of a weak-field shift for C3 by 9.0-9.7 ppm. Signals of
anomeric C1′ atoms of
appeared at δ 99.4-99.8 ppm. Spectra of
lacked signals for acetates but retained signals for
methoxyls of the aglycon in
(δ 176.6 ppm). Anomeric protons of
were observed in PMR spectra at δ 4.94 ppm as
a doublet with J
= 2.0-2.6 Hz, which indicated that they were equatorial and, therefore, that the C1′–O bond to the aglycon