Fournet, A.

Jacquemin, Henri

Pascard, C.

Polonsky, J.

Prange, T.

Varenne, J.

Horizon / Pleins textes

731 J.C.S. CHEM. COMM., 1981 
Isolation and Structure (X-Ray Analysis) of Manicoline A, a New 
cr -Aminotropone from Dulacia guianensis (Olacaceae) 
By JUDITH POLONSKY,* JEANNETTE VARENNE, THIERRY PRANG&, and CLAUDINE PASCARD 
(Institut de Chimie des Substances Naturelles, C N R S ,  91190 Gif-sw-Yvette, France) 
and HENRI JACQUEMIN and ALAIN FOURNET 
(Ofice de la Recherche Scienti3que et Technique Outre-Mer, B.P. 165, Cayenne, Guyane) 
Summary Two alkaloids, manicoline A and B, have been 
isolated from the root bark of Dulacia-guianensis (Ola- 
caceae); the structure of manicoline "A, a novel a- 
aminotropone, has been established by X-ray analysis. 
Dulacia guianensis (Engl.) O. Ktze (Olacaceae) is a fairly 
rare Guyanan tree? growing in the forests of Gallion, south 
of Cayenne. Previous studies of its root bark resulted in 
the isolation and structural determination of a eudesmane- 
type sesquiterpene with an aromatic A-ring, manico1 (1) .l 
Continuing our work on the constituents of D. guianensis 
we have now isolated two alkaloids which we have designated 
manicoline A and B. We herein report the structural 
elucidation of the major alkaloid, manicoline A. 
Chromatography of the alkaloidal extract (1.4 g) obtained 
from hexane-defatted, ground root bark (1 kg) of D .  
OH 
13 13 15 
(1) (2) 
guianensis over silica gel gave manicoline A and B (120 
and 58 mg, respectively). Further purification by column 
chromatography over Sephadex LH 20 and crystallisation 
from ethyl acetate afforded pale yellow crystals of mani- 
coline A (2) ,  m.p. 197-199 "C, [a]$2 f 69' (c 0.9, CHCl, + 
10% MeOH). 
The molecular formula of (2) (C,,H,,NO,) was established 
by microanalysis and by mass spectrometry [ w / e  247.1573 
H,O - CH,), and 186.1280 (91%; M - H,O - CH, - CO)]. 
Fragmentation ions a t  m/e 188-1093 (16%; M - C,H,O) 
and 59.0506 (28% ; C,H,O) were also observed. 
The U.V. spectrum (EtOH) of (2)  showed maxima a t  252 
( E  32 110), 340 (13 170), and 420 nm (10 700), and shoulders 
a t  266 (21 406) and 277 nm (10 700). The 400 MHz lH 
n.m.r. spectrum showed signals due to three methyl groups 
(6 1.26, 1.28, and 2-36) assigned to 12-, 13-, and 15-H,, 
respectively. It also revealed two one-proton singlets a t  
6 6.69 and 7.24 due to H-3 and H-14, respectively, and a two- 
proton signal a t  6 8-44 exchangeable with D,O (NH, group). 
Manicoline A gave a red-brown colour with alcoholic FeCl,, 
was negative to ninhydrin reagent on t.1.c. (vinylogous 
amide), but could be extracted from a CH,Cl, solution by 
dilute HC1. 
The structure of manicoline A (2) was determined by X -  
ray analysis using crystals obtained from ethyl acetate. 
( M f ) ,  229.1475 (60%; M - H,O), 214.1238 (70%; M - 
t A sample (No. H J 2165) of the material studied was deposited in .the Herbier du Museum d'Histoire Naturelles, Park. 
J.C.S. CHEM. COMM., 1981 732 
Crystal data: monoclinic, space group P2,, a = 13.436, 
b = 11.305, c = 9.363 A, ß = 103.8’ for Z = 4. Two in- 
dependent molecules with a different hydrogen bond net- 
work were observed in the asymmetric unit. Intensity 
data for 2197 independent reflections were measured using 
Cu-K, radiation. Lorentz and polarisation corrections were 
applied to 1817 reflections with I 2 2 4 .  The structure 
was solved by direct methods using the multisolution 
technique2 and was isotropically refined to R = 15%. 
Hydrogen atoms were introduced a t  their theoretical posi- 
tions (except those of ,the methyl groups) and the structure 
was refined with anisotropic thermal factors for the non- 
hydrogen atoms t0.a final conventional R factor of 10.1%. 
Although the determination of the nature and position of 
the heavy atoms did not present any particular difficulties, 
some discrepancies arose in establishing the bond distances 
of the two molecules in the unit cell; this was due to the 
bad mosaic structure of the crystal used in this study. 
The molecular structure of (2) is shown in the Figure.$ 
Manicoline A is the first naturally occuring cr-aminotropone. 
Nfl\ .....
FIGURE. Molecular structure of manicoline A, (2), showing the 
crystallographic numbering scheme. 
Manico1 (1) obviously anses biogenetically from the 
sesquiterpene eudesmol (3) which undergoes a dienone- 
phenol rearrangement to give the aromatic ring. It seems 
reasonable to suppose that eudesmol (3) is also the precursor 
of manicoline A (2). Two routes, (A) or (B) (Scheme) can 
be envisaged. In the first a cyclopropane ring is formed as 
for cycloartenol, and the ketone function is then introduced. 
In the second the ketone function is used to facilitate cyclo- 
propane formation. Both routes afford the hypothetical 
intermediate (4). By hydride abstraction at  C-5 and re- 
arrangement the second intermediate (5) would result. By 
epoxidation and amination manicoline A (2) would be 
formed. 
Manicoline A (2) is not cytotoxic for chick embryo fibro- 
blasts up to doses of 5 pg/ml and does not inhibit cell 
, R O H  
\ 
SCHEME. X = leaving group. 
transformation induced by the Rous sarcoma virus.s Studies 
of other kinds of biological activity are in progress. 
We are grateful to Professor D. H. R. Barton for helpful 
discussions concerning the biogenetic hypothesis, Mr. S. K. 
Kan (Laboratoire de R.M.N. à Haut Champ, Orsay) for the 
400 MHz 1H n.m.r. spectrum, Mr. P. Varenne for the high 
resolution mass spectrum, and Mrs. M. Robert-GBro for the 
biological tests. 
(Received, 1st May 1981; Com. 521.) 
$ The atomic co-ordinates for this work are available on request from the Director of the Cambridge Crystallographic Data Centre, 
Any request should be accompanied by the full literature University Chemical Laboratory, Lensfield Road, Cambridge CB2 1EW. 
citation for this communication. 
J. Polonsky, 2. Varon, H. Jacquemin, D. M. X. Donnelly, and M. J. Meegan, J .  Chem. Soc., Perkin Trans. 1, 1980, 2066. 
M. Robert-Géro, F. Lawrence, G. Farrugia, A. Berneman, P. Blanchard, P. Vigier, and E. Lederer, Biochem. Biophys. RES. Gommzcn., 
a G. Germain, P. Main, and M. Woolfson, Acta Crystallogr., Sect. A ,  1971, 27, 368. 
1976, 65, 1342’. 
Isolation and Structure (X-Ray Analysis) of Manicoline A, a New 
a-Aminotropone from Dulacia guianensis (Olacaceae) 
By JUDITH POLONSKY,* JEANNETTE VARENNE, THIERRY PRANG& and CLAUDINE PASCARD 
(Institut de Chimie des Substances Naturelles, C N R S ,  91190 Gif-sur-Yvette, France) 
'and HENRI JACQUEMIN and ALAIN FOURNET 
(Ofice de la Recherche Sciewtijíque et Technique Outre-Mer, B.P. 165, Cayenne, Guyane) 
Reprinted from the Journal of The Chemical Society 
Chemkcd Communications 7987 
2..1 OCT. 1984 
o. R. 3, T. b. M. fonds ~~~~e~~~~~ 


Isolation and structure (X-Ray analysis) of manicolina A, a new-aminotropone from Dulacia guianensis (Olacaceae)

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