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3-epi-β-yohimbine from roots of Rauwolfia linearifolia
$3.00 + 0.00 003I 9422,91 .(‘. 1991Pergamon Press plc
VoI .W.~GII4, pp 1352 1353.1991 Ph~roc%rmi.srr~. Pnnted in Grcar Britain.
3-WI-P-YOHIMBINE
FROM
ROOTS
OF RAU WOLFZA
LINEARZFOLIA
JORGE A. MARTINEZ PEREZ, CARLOS G~MEZ GONZALEZ, MARIA E. S~SA RODRIGUEZ and LETICIA T. NODA LLERENA Faculty
of Pharmacy.
University
(Rewired
Key Word I&x-Rauwo[fia
Abstract -----Anew natural
structure
elucidated
linearifolia;
yohimbine, by spectroscopic
of Havana,
Cuba
8 June 1990)
Apocynaceae;
roots; indole alkaloid;
3-epi-fi-yohimbine, was isolated and chemical studies.
The investigation of the alkaloidal fraction of the root of an endemic Cuban Apocynaceae, namely, Rauwolja linearijolia Britton and Wilson, led to the isolation of several known bases and a new natural compound, 3-e@b-yohimbine (1) [yohimbdn-l&carboxylic acid-17hydroxy, methyl ester (3,$16a,17/I)] Cl). It has been obtained as a crystalline solid, mp 201-203”. The UV spectrum J.k:” nm (log E): 227 (4.54), 282 (3.90) and 290 (3.81) indicated an unsubstituted indole chromophore. The IR spectrum showed absorptions at vi:: cm ’ : 3350 and 3150 (NH/OH), 1735 (C=O) and 750 (o-substituted benzene). The mass spectrum displayed CM] + at m/z 354. corresponding to the formula C,, HZ60,N,, and prominent peaks at m/z 353,295, 184,170, I69 and 156, typical of alkaloids with a tetrahydro-/&carboline nucleus in its structure [I]. The ‘H NMR spectrum showed signals (6, TMS) of the N-H indolic proton (7.95, br s, lH), four aromatic hydrogens (7.c7.5) and a methoxycarbonyl function (3.82, s, 3H). The above characteristics are in close agreement with those reported for the isomeric yohimbines [2]. In addition, the absence of Bohlmann’s bands in the IR spectrum and the presence of a signal at 64.44 (m, IH) in the ‘H NMR spectrum of compound I are considered to be diagnostic of a cis-C/D-junction in its structure [3,4], whereas a double triplet at 63.60 (lH, J, zJ z z IO Hz; J,=4.5 Hz) indicates an axial orientation of H- I7 in ring E of the alkaloid [4]. The analysis of the “C NMR spectra (SFORD and INEPT modes) was partially based on the literature for other yohimbine-type alkaloids [S, 63 and it clearly showed that 1 belongs to the pseudo-series, with both methoxycarbonyl and hydroxyl groups in equatorial positions. The chemical shifts of C-3 and C-6 in 1 arc quite similar to those observed in pseudoyohimbine (3) (Table I), showing in both cases the characteristic shielding for alkaloids with a cis-C,/Djunction. Chemical shifts of C-l 5, C-17 and C-19 in 1 resemble those of p-yohimbine (2), in both cases downfield when compared with those in the spectrum of 3. The former is due to the s_vn-diaxial steric interactions of the axial l7-hydroxyl group in 3 which are absent in 1 and 2. On the other hand, the chemical shifts of C-14, C-18 and C-20 in 1 adequately resembled the corresponding deshielded signals observed in the spectra of 2 and 3, thus revealing the presence of an equatorial methoxycarbonyl group in 1. Supplementary evidence of the structure 1352
3-epi-/?-yohimbine.
from the root of Rauwolfia linearifolia and its
C;;1
H-3 OH-17
Table
c 2 3 5 6 7 8 9 10 II 12 13 14 15 16 17 18 19 20 21 c=o OMe
1
B
B
2
Q
B
3
B
(I
1. “CINMR
spectral data of compounds and 3 [6] (CDCI,)
I, 2 [S]
I
2
3
135.8 55.x 50.9 17.1 107.8 127.6 118.0 119.3 121.4 111.2 135.x 32.0 36.8 56.9 71.9 30.8 28.0 39.5 53.5 173.7 51.9
134.0 59.0 52.3 21.3 107.4 126.9 I 17.7 118.8 120.9 110.7 135.8 33.8 41.6 57.1 71.6 33.5 27.5 39.1 60.5 175.0 51.6
135.0. 54.6 51.0 16.9 108.0. 127.0.
*The exact posttion
the original paper.
117.0’ 119.0* 12 I .o* 111.0* 135.0; 31.6 32.5 52.1 67.0 3 I .4 23.0 40.2 52.0 174.9 51.9
of these signals was not detined
in
Short
proposed for alkaloid 1 was obtained after chemical interrelation with 2. Following a reported procedure [7], a sample of natural p-yohimbine was dehydrogenated by treatment with mercury(H) acetate, then reduced with zinc powder in acetic acid to give a mixture of 1 and 2, which was separated by PLC. Crystalline synthetic 3-e@/l-yohimbine was undistinguishable in mp, chromategraphic and spectral data from the naturally occurring base. Although 3-epi-B-yohimbine has been synthesized previously [I, this is, to our knowledge, its first recognition as a natural product. EXPERIMENTAL
NMR spectra were recorded in CDCI,. The mass spectra were taken with a spectrometer
Mp: uncorr.
fitted with direct inlet system (70 eV).
1353
Reports REFERENCES
1 Budzikiewicz, ’
H., Djerassi, C. and Williams, D. H. (1964) Structure Elucidation of Natural Products by Mass Spectramerry Vol. 1. Holden-Day. San Frdncisco. *, Gabetta, B. and Mustich, G. (1975) Spectral Data of Indole Alkaloids. Inverni Della Be& Milan. 3, Bohlmann, F. (1957). Angew. Chem. 69, 641. 4, Albright, J. D., M&her, L. A. and Goldman, L. (1%3)J. Org. Chem. 28.38.
5
Honty, K., Baitz-Can, E., Blasko, G. and Szantay, C. (1982) J. Org. Chem. 47, 5111. 6. Amone, A., Nasini, G. and Merlini, L. (1987) J. C&m. Sot., Perkin
Trans I 571.
7. Janet, M. M., Goutarel, R., Warnhoff, (1961) Bull. Sot. Chim. Fr. 637.
E. F. and Le Hir, A.
VoI .W.~GII4, pp 1352 1353.1991 Ph~roc%rmi.srr~. Pnnted in Grcar Britain.
3-WI-P-YOHIMBINE
FROM
ROOTS
OF RAU WOLFZA
LINEARZFOLIA
JORGE A. MARTINEZ PEREZ, CARLOS G~MEZ GONZALEZ, MARIA E. S~SA RODRIGUEZ and LETICIA T. NODA LLERENA Faculty
of Pharmacy.
University
(Rewired
Key Word I&x-Rauwo[fia
Abstract -----Anew natural
structure
elucidated
linearifolia;
yohimbine, by spectroscopic
of Havana,
Cuba
8 June 1990)
Apocynaceae;
roots; indole alkaloid;
3-epi-fi-yohimbine, was isolated and chemical studies.
The investigation of the alkaloidal fraction of the root of an endemic Cuban Apocynaceae, namely, Rauwolja linearijolia Britton and Wilson, led to the isolation of several known bases and a new natural compound, 3-e@b-yohimbine (1) [yohimbdn-l&carboxylic acid-17hydroxy, methyl ester (3,$16a,17/I)] Cl). It has been obtained as a crystalline solid, mp 201-203”. The UV spectrum J.k:” nm (log E): 227 (4.54), 282 (3.90) and 290 (3.81) indicated an unsubstituted indole chromophore. The IR spectrum showed absorptions at vi:: cm ’ : 3350 and 3150 (NH/OH), 1735 (C=O) and 750 (o-substituted benzene). The mass spectrum displayed CM] + at m/z 354. corresponding to the formula C,, HZ60,N,, and prominent peaks at m/z 353,295, 184,170, I69 and 156, typical of alkaloids with a tetrahydro-/&carboline nucleus in its structure [I]. The ‘H NMR spectrum showed signals (6, TMS) of the N-H indolic proton (7.95, br s, lH), four aromatic hydrogens (7.c7.5) and a methoxycarbonyl function (3.82, s, 3H). The above characteristics are in close agreement with those reported for the isomeric yohimbines [2]. In addition, the absence of Bohlmann’s bands in the IR spectrum and the presence of a signal at 64.44 (m, IH) in the ‘H NMR spectrum of compound I are considered to be diagnostic of a cis-C/D-junction in its structure [3,4], whereas a double triplet at 63.60 (lH, J, zJ z z IO Hz; J,=4.5 Hz) indicates an axial orientation of H- I7 in ring E of the alkaloid [4]. The analysis of the “C NMR spectra (SFORD and INEPT modes) was partially based on the literature for other yohimbine-type alkaloids [S, 63 and it clearly showed that 1 belongs to the pseudo-series, with both methoxycarbonyl and hydroxyl groups in equatorial positions. The chemical shifts of C-3 and C-6 in 1 arc quite similar to those observed in pseudoyohimbine (3) (Table I), showing in both cases the characteristic shielding for alkaloids with a cis-C,/Djunction. Chemical shifts of C-l 5, C-17 and C-19 in 1 resemble those of p-yohimbine (2), in both cases downfield when compared with those in the spectrum of 3. The former is due to the s_vn-diaxial steric interactions of the axial l7-hydroxyl group in 3 which are absent in 1 and 2. On the other hand, the chemical shifts of C-14, C-18 and C-20 in 1 adequately resembled the corresponding deshielded signals observed in the spectra of 2 and 3, thus revealing the presence of an equatorial methoxycarbonyl group in 1. Supplementary evidence of the structure 1352
3-epi-/?-yohimbine.
from the root of Rauwolfia linearifolia and its
C;;1
H-3 OH-17
Table
c 2 3 5 6 7 8 9 10 II 12 13 14 15 16 17 18 19 20 21 c=o OMe
1
B
B
2
Q
B
3
B
(I
1. “CINMR
spectral data of compounds and 3 [6] (CDCI,)
I, 2 [S]
I
2
3
135.8 55.x 50.9 17.1 107.8 127.6 118.0 119.3 121.4 111.2 135.x 32.0 36.8 56.9 71.9 30.8 28.0 39.5 53.5 173.7 51.9
134.0 59.0 52.3 21.3 107.4 126.9 I 17.7 118.8 120.9 110.7 135.8 33.8 41.6 57.1 71.6 33.5 27.5 39.1 60.5 175.0 51.6
135.0. 54.6 51.0 16.9 108.0. 127.0.
*The exact posttion
the original paper.
117.0’ 119.0* 12 I .o* 111.0* 135.0; 31.6 32.5 52.1 67.0 3 I .4 23.0 40.2 52.0 174.9 51.9
of these signals was not detined
in
Short
proposed for alkaloid 1 was obtained after chemical interrelation with 2. Following a reported procedure [7], a sample of natural p-yohimbine was dehydrogenated by treatment with mercury(H) acetate, then reduced with zinc powder in acetic acid to give a mixture of 1 and 2, which was separated by PLC. Crystalline synthetic 3-e@/l-yohimbine was undistinguishable in mp, chromategraphic and spectral data from the naturally occurring base. Although 3-epi-B-yohimbine has been synthesized previously [I, this is, to our knowledge, its first recognition as a natural product. EXPERIMENTAL
NMR spectra were recorded in CDCI,. The mass spectra were taken with a spectrometer
Mp: uncorr.
fitted with direct inlet system (70 eV).
1353
Reports REFERENCES
1 Budzikiewicz, ’
H., Djerassi, C. and Williams, D. H. (1964) Structure Elucidation of Natural Products by Mass Spectramerry Vol. 1. Holden-Day. San Frdncisco. *, Gabetta, B. and Mustich, G. (1975) Spectral Data of Indole Alkaloids. Inverni Della Be& Milan. 3, Bohlmann, F. (1957). Angew. Chem. 69, 641. 4, Albright, J. D., M&her, L. A. and Goldman, L. (1%3)J. Org. Chem. 28.38.
5
Honty, K., Baitz-Can, E., Blasko, G. and Szantay, C. (1982) J. Org. Chem. 47, 5111. 6. Amone, A., Nasini, G. and Merlini, L. (1987) J. C&m. Sot., Perkin
Trans I 571.
7. Janet, M. M., Goutarel, R., Warnhoff, (1961) Bull. Sot. Chim. Fr. 637.
E. F. and Le Hir, A.