Selective oxidation of triterpene alcohols by sodium hypochlorite

Article abstract of DOI:10.1023/B:CONC.0000033930.76751.b7

3-Oxo-triterpenoids were prepared by oxidation of the methyl esters of glycyrrhetic acid, allobetulin, and 20-oxo-29-nor-betulin with sodium hypochlorite in acetic acid or methylene chloride under phase-transfer conditions.

Full text of DOI:10.1023/B:CONC.0000033930.76751.b7

Chemistry of Natural Compounds, Vol. 40, No. 2, 2004
SELECTIVE OXIDATION OF TRITERPENE ALCOHOLS
BY SODIUM HYPOCHLORITE
O. B. Flekhter,1 O. Yu. Ashavina,1 I. E. Smirnova,1
L. A. Baltina,1 F. Z. Galin,1 N. N. Kabal′nova,1
and G. A. Tolstikov2
UDC 547.918:547.914.4.057
3-Oxo-triterpenoids were prepared by oxidation of the methyl esters of glycyrrhetic acid, allobetulin, and
20-oxo-29-nor-betulin with sodium hypochlorite in acetic acid or methylene chloride under phase-transfer
conditions.
Key words: oxidation; sodium hypochlorite; selectivity; methyl esters ofglycyrrhetic acid, allobetulin, 20-oxo-29-nor-
betulin.
Sodium hypochlorite is used successfully for oxidation under mild conditions of secondary alcohols to ketones [1-3]
and allylic chlorination of terminal olefins [4]. The oxidation of triterpene alcohols by NaOCl has not been reported.
Traditional oxidants such as Cr(VI) [6], -CPBA ( -chloroperbenzoic acid) [7], "activated" dimethylsulfoxide [8] and others,
m
m
which often lead to several side products [7-9], are used to prepare 3-oxo-derivatives of triterpenoids, which are valuable
intermediates in the synthesis of several biologically active compounds [5].
We observed that NaOCl oxidizes the 3β-hydroxyl of certain triterpenoids. The methyl esters of glycyrrhetic acid (1),
allobetulin (2), and 20-oxo-29-nor-betulin (messagenin) (3) give 3-oxo-derivatives 4-6. The reaction was carried out in acetic
acid [10] or methylene chloride in the presence of the phase-transfer catalyst hexadecyltrimethylammonium bromide [11] using
three equivalents of NaOCl. The formation of the ketone on C-3 in compounds 4-6 was inferred from the presence of a signal
at 217.1-218.2 ppm and the absence of a signal for proton H-3 at 3.10-3.20 ppm, which is observed in NMR spectra of the
starting triterpene alcohols. Signals belonging tothe primaryalcohol in NMRspectra of6 persist, confirming that the oxidation
is selective. This is consistent with the known reactivity of NaOCl [10].
O
COOCH
3
20
30
H 19
H
O
12
18
O
28
CH OH
2
28
3
3
3
X
X
X
1, 4
2, 5
3, 6
OH
H
1 - 3: X =
4 - 6: X = O
1) Institute of Organic Chemistry, Ufa Scientific Center, Russian Academy of Sciences, 450054, Ufa, pr. Oktyabrya,
71, fax (3472) 35 60 66, e-mail: obf@anrb.ru; 2) N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian
Division, Russian Academy of Sciences, 630090, Novosibirsk, pr. Akad. Lavren′teva, 9. Translated from Khimiya Prirodnykh
Soedinenii, No. 2, pp. 121-122, March-April, 2004. Original article submitted January 27, 2004.
0009-3130/04/4002-0141 ©2004 Plenum Publishing Corporation
141

EXPERIMENTAL
13
PMR and C NMR spectra were recorded on an AM-300 spectrometer (Bruker, 300 and 75.5 MHz, respectively) in
CDCl with SiMe internal standard. Melting points were determined on a Boetius microstage. TLC was performed on Silufol
3
4
plates (Chemapol, Czech Rep.) using the solvent systems CHCl :CH OH (20:1, A; 25:1, B). Compounds were detected using
3
3
phosphotungstate solution in EtOH (10%) with subsequent heating at 100-120°C for 2-3 min. Aqueous NaOCl (1 M, OAO
Ufakhimprom, Rep. of Bashkortostan) was used in the experiments.
The methyl esters of glycyrrhetic acid (1), allobetulin (2), and 20-oxo-29-nor-betulin (3) were prepared as before [12-
14]. Elemental analyses agreed with those calculated.
Oxidation of 1-3. Method a) A solution of 1-3 (1 mmol) in acetic acid (10 mL) was stirred and treated dropwise with
NaOCl solution (0.60 mL, 3 eq., 1M), held at room temperature for 1 h, and treated with KOH solution (50 mL, 5%). The
resulting precipitate was filtered off, washed with water until the washings were neutral, and dried. Yield 90-95%.
Method b) A suspension of hexadecyltrimethylammonium bromide (0.020 mmol) in CH Cl (10 mL) and water
2
2
(10 mL) was stirred, treated with 1-3 (1 mmol) and then dropwise with NaOCl solution (0.60 mL, 3 eq., 1 M), and held at room
temperature for 1-2 h (TLC monitoring). The organic layer was separated, washed with water (2 × 10 mL), dried over MgSO ,
4
and evaporated in vacuum. The solid was dissolved in CHCl (10 mL), passed over a layer of aluminum oxide (1 cm), and
3
evaporated in vacuum. Yield 76-81%.
Methyl Ester of 3,11-Dioxo-18β-olean-12-en-20β-oic Acid (4). Yield 0.45 g (93%) (method a) and 0.37 g (76%)
(method b) from 1, R 0.85 (system A), mp 248°C, lit. [15] mp 248-249°C, C H O .
f
31 46
4
PMR spectrum (δ, ppm, J/Hz): 0.80, 1.04, 1.08, 1.13, 1.14, 1.25, 1.35 (7s, 21H, 7CH ), 1.15-2.10 (m, CH, CH ), 2.32
3
2
(s, 1H, H-9), 2.80 (d, 1H, J = 13.5, H-18), 3.67 (s, 3H, OCH ), 5.68 (br.s, 1H, H-12).
3
13
C NMR spectrum (δ, ppm): 15.6. 18.5, 18.7, 21.3, 21.4, 23.4, 26.4, 26.5, 28.2, 28.5, 31.0, 31.7, 32.0, 34.1, 36.4,
37.6, 39.6, 41.1, 43.2, 44.9, 45.2, 47.7, 48.3, 51.8, 55.3, 61.0 (C-9), 128.4 (C-12), 169.5 (C-13), 176.8 (C-30), 199.4 (C-11),
217.1 (C-3).
19β,28-Epoxy-18α-olean-3-one (5). Yield 0.42 g (95%) (method a) and 0.35 g (79%) (method b) from 2, R 0.82
f
(system B), mp 230°C, lit. [16] mp 230-231°C, C H O .
30 48
2
PMR spectrum (δ, ppm, J/Hz): 0.80, 0.92, 0.93, 0.95, 1.02, 1.04, 1.10 (7s, 21H, 7CH ), 1.15-2.00 (m, CH, CH ), 2.46
3
2
(m, 2H, H-2), 3.47 and 3.80 (both d, 1H each, J = 6, H-28), 3.55 (s, 1H, H-19).
13
C NMR spectrum (δ, ppm): 13.00, 15.4, 16.2, 18.6, 19.4, 20.8, 21.2, 21.6, 24.1, 25.3, 25.7, 25.8, 25.9, 28.2, 32.2,
33.0, 33.5, 35.8, 36.2, 38.7, 40.2, 40.4, 41.0, 46.8, 48.8, 51.7, 56.6, 70.6 (C-28), 87.4 (C-19), 218.0 (C-3).
3,20-Dioxo-29-nor-lup-28-ol (6). Yield 0.41 g (92%) (method a) and 0.36 g (81%) (method b) from 3, R 0.52
f
(system B), mp 125°C, C H O .
29 46
3
PMR spectrum (δ, ppm, J/Hz): 0.67, 0.74, 0.88, 0.91, 0.92 (5s, 15H, 5CH ), 1.00-2.00 (m, CH, CH ), 2.16 (s, 3H,
3
2
H-30), 2.40-2.45 (m, 1H, H-19), 3.25 (d, 1H, J = 11, H-28), 3.80 (d, 1H, J = 11, H-28).
13
C NMR spectrum (δ, ppm): 14.5, 15.8, 15.9, 16.3, 17.9, 19.6, 21.3, 26.8, 27.0, 27.3, 27.7, 28.7, 29.5, 33.3, 33.8,
36.1, 36.9, 37.6, 38.1, 40.6, 42.4, 46.1, 49.2, 49.9, 51.5, 55.1, 60.5 (C-28), 211.0 (C-20), 218.2 (C-3).
ACKNOWLEDGMENT
The work was supported by the Russian Basic Research Foundation (project 02-03-81007) and grants of the RF
President and Young Russian Scientists and Leading Scientific Schools (projects MK-543.2003.03, NSh-1488.2003.3). We
thank the Russian Foundation for Science Support (Young Investigators Program).
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