Synthesis of certain monoterpenoid glucosides

Article abstract of DOI:10.1007/s10600-006-0173-8

The monoterpenols borneol, verbenol, 4-(1-hydroxyethyl)carene-2, and myrtenol were glucosylated using acetobromoglucose. The structures of the prepared derivatives were established using PMR and ¹³C NMR spectroscopy.

Full text of DOI:10.1007/s10600-006-0173-8

Chemistry of Natural Compounds, Vol. 42, No. 4, 2006
SYNTHESIS OF CERTAIN MONOTERPENOID GLUCOSIDES
S. A. Patov, V. V. Punegov, A. V. Kuchin, and L. L. Frolova
UDC 247.918
The monoterpenols borneol, verbenol, 4-(1-hydroxyethyl)carene-2, and myrtenol were glucosylated using
13
acetobromoglucose. The structures of the prepared derivatives were established using PMR and C NMR
spectroscopy.
Key words: monoterpenoids, glucosylation.
Monoterpenoids are found in essential oils of many medicinal plants and medicinal agents based on them.
Monoterpene glucosideshavebeen isolatedfrom themedicinal plants
L.,
, which possess distinct
Origanumvulgare Rosa gallica
fungicidal properties [1, 2]; and
others [3, 4].
, which has a unique structure and possesses adaptogenic activity among
Paeona peregrine
The physiological activity of monoterpene glucosides was studied by synthesizing glucosides of the terpene alcohols
borneol (1), verbenol (2), 4-(1-hydroxyethyl)carene-2 (3), and myrtenol (4), which have chemical structures identical to the
natural ones except for 3.
Glucosides were synthesized using the Koenig—Knorr method [5] and silver carbonate catalyst. Unreacted
monoterpenoids were removed after the reactions were completed by steam distillation. Then, compounds were purified over
silica-gel columns with elution by CHCl :CH OH of increasing polarity.
3
3
We believe that the scatter in the product yields is explained by steric hindrances in the structures of the actual
monoterpenoids. In particular, the hydroxyl in 2 is more reactive because it is allylic and as far as possible from the
-dimethyl on C-6. Therefore, the yield ofverbenol glucoside is slightlygreater than that ofthe other alcohols. The low yield
gem
of borneol (1) glucoside is explained by the fact that the C-2 hydroxyl has the
-configuration that is known to be sterically
endo
shielded. Compounds 3 and 4 give similar yields:
Compound
Yeld, %
5
6
7
8
35
58
42
42
OAc
OAc
O
O
Ag CO
2
3
AcO
AcO
AcO
OR
ROH
+
AcO
1 - 4
OAc
Br
OAc
5 - 8
9
8
7
10
10
OH
OH
10
10
3
3
3
1
1
1
11
12
3
6
5
6
1
9
OH
7
5
7
5
OH
8
5
7
4
1
2
3
Institute of Chemistry, Komi Scientific Center, Urals Division, Russian Academy of Sciences, 167000, Syktyvkar, ul.
Pervomaiskaya, 48, fax(88212)436677, e-mail:patov-sa@chemi.komisc.ru. Translatedfrom KhimiyaPrirodnykh Soedinenii,
No. 4, pp. 348-349, July-August, 2006. Original article submitted April 24, 2006.
0009-3130/06/4204-0431 ©2006 Springer Science+Business Media, Inc.
431

TABLE 1. 13C NMR and PMR Chemical Shifts of Monoterpenoid Glycosides, ppm*
Compound
C atom
5
6
7
8
13C
1H
13C
1H
13C
1H
13C
1H
1
49.0
72.6
39.1
47.9
26.3
28.2
47.9
20.3
18.8
15.0
-
-
47.7
149.7
114.8
76.6
46.6
35.5
27.6
26.6
22.8
22.4
-
1.8
-
213.0
122.4
137.5
45.3
0.9
5.2
-
42.1
142.8
123.1
34.7
40.8
37.6
26.5
24.0
23.4
68.3
-
2.4
-
2
3.8
1.5
1.6
1.7
1.5
-
3
5.5
4.0
2.8
-
5.6
2.0
3.2
-
4
2.4
1.7
0.6
-
5
27.6
6
21.3
7
1.6
1.1
1.2
1.7
-
22.3
1.5
1.0
1.0
3.9
-
8
0.8
0.9
1.0
-
20.0
1.0
1.1
1.6
3.6
0.7
4.6
4.5
5.0
4.8
3.5
4.2
-
9
20.6
10
68.7
11
20.7
12
-
-
-
-
20.7
-
-
1
102.3
71.8
71.2
68.6
72.6
62.0
169-170
19-21
4.7
4.4
5.0
4.7
3.7
4.2
-
98.9
71.0
69.8
68.4
72.9
61.9
169-170
19-21
4.2
4.3
4.8
4.8
3.5
4.0
-
98.8
101.1
71.9
70.9
67.1
69.7
61.9
169-170
19-21
4.4
4.8
5.4
5.0
4.0
4.1
-
2
69.8
3
68.8
4
5
67.2
71.0
6
61.9
O-C=O
OCH3
169-170
19-21
2.0
2.0
2.0
2.0
______
*Acetates in acylated glycosides were removed by a Zemplen reaction [6].
13
According to PMR and C NMR spectra, the resulting glucosides have a β-D-glucoside bond. This was confirmed
by the presence in the spectra of signals at 4.2-4.6 ppm (J1′2′ = 8-8.5 Hz) and 99-101 ppm, respectively (Table 1). According
to the literature, most glucosides isolated from medicinal plants have the β-D-configuration.
EXPERIMENTAL
13
C NMRand PMRspectra were recorded on a Bruker DRX 400 spectrometer at working frequency400 and 100 MHz,
respectively, in CDCl . TLC was performed on Silufol (Czech Rep.) plates using CHCl :CH OH (9:1 and 6:1); column
3
3
3
chromatography, over silica gel L (100/160 µm) using mixtures of CHCl :CH OH (10:1-4:1). Compounds were detected by
3
3
phosphotungstic acid solution (20%) in ethanol with heating at 120°C for 1 min.
2,3,4,6-Tetra-O-acetyl-α-D-glucopyranosylbromide was prepared by the literature method [7], silver carbonate, by
reacting silver nitrate (2 g) with saturated Na CO solution (100 mL) in the dark. The resulting yellow powder was dried with
2
3
anhydrous acetone and then lyophilized. Diethylether was distilled from metallic Na.
Synthesis of 5-8. A weighed portion of starting alcohol (50 mg) in absolute diethylether (20 mL) was stirred and
treated with glycosylating agent (2,3,4,6-tetra-O-acetyl-α-D-glucopyranosylbromide, 0.7 mol amount) and AgCO (2-fold
3
excess, 71 mg). The reaction mixture was stirred at room temperature for 1 d. The course of the reaction was monitored by
TLC. After the reaction was finished, solvent was evaporated. The excess of monoterpenoids was steam distilled. The solid
was placed on a SiO column and eluted by CHCl :CH OH (20:1-6:1).
2
3
3
Removal of Acetates. A solution of acetylated glucoside in anhydrous CH OH (25 mL) was treated with a solution
3
prepared by dissolving metallic Na (10 mg, 0.435 mmol) in CH OH (absolute, 25 mL) and stirred for 5 h at room temperature.
3
The reaction mixture was neutralized by adding cation-exchanger KU-2 (1 g) in the H-form. Yield 95-97%.
432

REFERENCES
1.
V. Manohar, C. Ingram, J. Gray, N. A. Talpur, B. W. Echard, D. Bagchi, and H. G. Preuss, Mol. Cell. Biochem.,
228, 111 (2001).
2.
3.
4.
5.
6.
7.
P. S. Bugorskii and V. N. Mel′nikov, Khim. Prir. Soedin., 864 (1977).
I. N. Kostova, M. F. Simeonov, D. I. Todorova, and P. L. Petkova, Phytochemistry, 48, No. 3, 511 (1998).
H.-C. Lin, H.-Y. Ding, T. Shung, and P.-L. Wu, Phytochemistry, 41, No. 1, 237 (1996).
N. K. Kochetkov, Methods of Carbohydrate Chemistry [in Russian], Mir, Moscow (1967).
L. F. Tietze and T. Eicher, Preparative Organic Chemistry [translated from Ger.], Mir, Moscow (1999).
Yu. A. Zhdanov, Practicum in Carbohydrate Chemistry [in Russian], Vysshaya Shkola, Moscow (1973).
433