An efficient one-pot synthesis of cyclovirobuxine A from buxozine C

Full text of DOI:10.1007/s10600-009-9202-8

Chemistry of Natural Compounds, Vol. 44, No. 6, 2008
AN EFFICIENT ONE-POT SYNTHESIS OF CYCLOVIROBUXINE A
FROM BUXOZINE C
Hai-Feng Liu, Xiao-Qing Wu, Yan-Bing Duan,
Ren-Bo Dou, Hai-Feng Sun, and Min Ji*
UDC 547.945
For many years, alkylation of 1,2-aminoalcohols was usually performed in high yield by catalytic hydrogenation of
oxazolidine. Cope et al. reported that the ring opening of oxazolidine under catalytic hydrogenation with platinum oxide
afforded 2-alkylaminoethanols as the only detectable product. The yield is nearly quantitive [1].
Theringopeningoftetrahydro-1, 3-oxazineispreviouslyperformedwith nucleophilicagentssuch aslithium aluminum
hydride [2] and bromozincioacetate [3, 4], which is a useful synthetic method to obtain 3-aminopropanol derivatives.
Buxozine-C (1), the first
alkaloid possessing a tetrahydro-oxazine ring joined to position 16a, 17b of the
Buxus
androstane skeleton, was first isolated from
L. Its structure elucidation was reported byVoticky[5] in 1977,
Buxus sempervirens
and it was obtained by semisynthesis from cyclovirobuxine D [6].
Cyclovirobuxine A (2), a alkaloid, was first isolated by Khuong-Huu-Laine [7] in 1966. It has potential
Buxus
application for the treatment of cardiovascular and cerebrovascular diseases [8].
Similar to platinum oxide, palladized carbon is an important hydrogenation catalyst. Meanwhile palladized carbon is
also an effective catalyst for reductive amination.
In the current attempt at the semisynthesis ofcyclovirobuxine Afrom buxozine C, the real issue is tochoose an efficient
catalyst reacting both on reductive ring cleavage and amination.
The above-mentioned data on platinum oxide led to speculation that palladized carbon may be an effective catalyst for
both direct ring opening of tetrahydro-1,3-oxazine and reductive amination of buxozine C.
Results showed that reductive amination and ring cleavage of compound 1 with 10% palladized carbon as catalyst
afforded alkaloid 2 in nearly quantitive yield (Scheme 1).
CH
N
3
24
N
(CH )
3 2
O
OH
H
H
HCHO, H
22
2
HN
HN
Pd/C, 90°
H
H
25
26
H C
3
(CH )
3 2
23
1
2
Scheme 1. Synthesis of cyclovirobuxine A (2) from buxozine C (1).
The postulated formulation of compound 2 is in accordance with the number of acid hydrogen found in the molecule.
1
Characteristically, The TOF-MS displayed a peak of the [M+H]+ at 431.7(C28H50N2OH+, requires 431.71). The H NMR
showed the presence of the hydroxy group at 4.49 ppm. The IR spectrum exhibited the vibration of the O-H bond (3414 cm–1)
and the
-amino group (1175 cm–1).
tert
Melting point was determined on an RY-1 melting point apparatus and is uncorrected. Infrared spectra were recorded
in KBr on a Nicolet Impact 410 spectrophotometer. NMR spectra were taken on Bruker AV-500 spectrometers (300 MHz for
Institute of Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Southeast University,
Nanjing 210096, China, e-mail: jimin@seu.edu.cn. Published in Khimiya Prirodnykh Soedinenii, No. 6, pp. 667-668,
November-December, 2008. Original article submitted July 18, 2007.
0009-3130/08/4406-0829 ©2008 Springer Science+Business Media, Inc.
829

1H and 125 MHz for 13C). Deuteriochloroform was used as the solvent. Chemical shifts are given in the δ-scale (ppm), and
coupling constants J in Hz. Assignment of C atoms in the 13C NMR spectra was based on previous studies with Buxus alkaloids
[9, 10]. API-MS was recorded on an Agilent 1100 LC-MS mass spectrometer.
Cyclovirobuxine A (2). In a high-pressure autoclave (1000 mL) containing 10% Pd/C (1g) and absolute ethanol
(300 mL) was added 37% aqueous formaldehyde (2.25 mL, 0.03 mol) and buxozine C (10.35 g, 0.025 mol). Stirring led to the
ring opening reaction with H2 at 2 atm pressure at 90°C. After 6 h, the mixture was filtered, the solvent evaporated, and the
residue recrystallized with acetone to afford 10.46 g (97%) of cyclovirobuxine A, mp 241–242°C (acetone, decomposed),
lit. [7] 244°C.
IRspectrum (KBr, νmax, cm–1): 3414, 2965, 2926, 2861, 2824, 2783, 2765, 1640, 1648, 1455, 1384, 1376, 1369, 1354,
1336, 1398,1255, 1175, 1151, 1100, 1029, 1003, 987, 897.
1H NMR (300 MHz, CDCl3, δ, ppm, J/Hz): 4.49 (1H, s, OH), 4.18 (1H, m, H-16), 2.76 (1H, m, H-20), 2.40 (3H, s,
H-23), 2.40 (3H, s, H-23′), 2.28 (3H, s, H-24), 2.28 (3H, s, H-24′), 1.09 (3H, s, H-22), 1.08 (3H, s, H-18), 0.99 (3H, s, H-26),
0.91 (3H, s, H-25), 0.64 (1H, d, J = 3.8, H-19), 0.39 (1H, d, J = 4.1, H-19′)
13C NMR (125 MHz, CDCl3): 79.1 (C-16), 71.9 (C-3), 62.4 (C-20), 57.1 (C-17), 49.5 (C-14), 48.2 (C-8), 47.3 (C-24,
C-24′), 44.9 (C-13), 44.7 (C-4), 44.3 (C-5), 41.9 (C-10), 33.4 (C-12), 31.6 (C-15), 30.3 (C-1), 26.9 (C-19), 26.3 (C-25, C-26),
26.2 (C-23, C-23′), 26.0 (C-6, C-7), 21.4 (C-2), 21.1 (C-9), 20.4 (C-11), 19.5 (C-22), 19.0 (C-18), 16.0 (C-21).
API-MS (m/z): 431.7 [M+H]+.
REFERENCES
1.
2.
3.
4.
5.
A. C. Cope and E. M. Hancock, J. Am. Chem. Soc., 64, 1503 (1942).
A. Alberola, M. A. Alvarez, C. Andres, A. Gonzolez, and R. Pedrosa, Synthesis, 153 (1990).
A. Alberola, M. A. Alvarez, C. Andres, A. Gonzolez, and R. Pedrosa, Synthesis, 1057 (1990).
M. J. Wu, D. S. Yan, H. W. Tsai, and S. H. Chen, Tetrahedron Lett., 35, 5003 (1994).
a. Z. Voticky, L. Dolejs, O. Bauerova, and V. Paulik, Collect. Czech. Chem. Commun., 42, 2549 (1977);
b. Z. Voticky, O. Bauerova, V. Paulik, and L. Dolejs, Phytochemisty, 16, 1860 (1977).
H. F. Liu, M. Ji, and J. Cai, Arch. Pharm. Chem. Life Sci., 339, 675 (2006).
6.
7.
Khuong-Huu-Laine, M. Marie-Josee, G. B. Norman, and G. Robert, Bull. Soc. Chim. Fr., 758 (1966).
8.
M. H. Chiu and R. L. Nie, Nat. Prod. Res. Dev., 4, 41 (1992).
9.
10.
Atta-ur-Rahman, S. Parveen, A. Khalid, A. Farooq, and M. I. Choudhary, Phytochemistry, 58, 963 (2001).
M. I. Choudhary, S. Shahnaz, S. Parveen, A. Khalid, S. A. M. Ayatollahi, Atta-Ur-Rahman, and M. Parvez,
J. Nat. Prod., 66, 739 (2003).
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