Fournet, Alain

Jacquemin, Henri

Pascard, C.

Polonsky, J.

Prangé, T.

Horizon / Pleins textes

9 
Tetrahedron LettersIVo1.25,No.22,pp 2359-2362,1984 0040-4039/84 $3.00 + .O0 
Printed in Great Britain 01984 Pergamon Press Ltd. 
STRUCTURE (X-RAY ANALYSIS) OF MANICOLINE B, A MIXTURE OF TWO 
DIASTEREOISOMERS OF A NEW ALKALOID FROM DULACIA GUIANENSIS (OLACACEAE) 
By Judith Polonsky*, Thierry Prangé, and Claudine Pascard 
(Institut de Chimie des Substances Naturelles, C.N.R.S. 
91190 Gif-sur-Yvette, France) 
and Henri Jacquemin and Alain Fournet 
(Office de la Recherche Scientifique et Technique 
Outre-Mer , B .P. 165, Cayenne, Guyane ) 
Summary : Manicoline B, isolated from the root bark of Dulacia guianensis 
(Olacaceae), was shown by X-ray analysis to be an equimolecular mixture of 
two diastereoisomers of a new alkaloid and to have structure (2). 
Previous studies' of the root bark of Dulacia guianensis (Engl.) O. Ktae 
(Olacaceae) resulted in the isolation, along with the sesquiterpenoid hydro- 
xytropolone manico1 (L)2, of two new alkaloids which have been designated 
manicoline A and B. The major alkaloid, manicoline A, C15H21N02, was shown 
to have structure and to be the first naturally occurring a-aminotropone. 
We herein report the structural elucidation of the minor alkaloid, manicoline 
B, (2) which proved to be a mixture of two diastereoisomers. 
(2) 
Manicoline B (3) crystallized from acetone as colourless crystals, 
m.p. Igg-2OO0, [a1E2Z+36" 
TLC in several solvent systems. The high resolution mass spectrum establi- 
shed the molecular formula of (2) as C H N O (M+' at m / z  275.1631) ; 
the CI mass spectrum showed the MH' ion at m / z  276 and the dimeric ion 
(2xM)H' at m/a 551- The U.V. spectrum (EtOH) of (2) displayed end absorp- 
tion around 220 nm and maxima at 228 (€2112) and 272 nm (1713). The 400 MHz 
'H n.m.r. spectrum showed signals due to the isopropylidene group : a methyl 
resonance at 
(c=0.23 ; CHC13) ; it displays a single spot on 
15 21 3 2 
6 1.78 and two one proton signals at 6 4.81 ( s )  and 4.75 (d, 
2359 
2 3 6 0  
J=5 H a ) .  It also revealed the presence of a tertiary methyl group (two sin- 
glets of same intensity at 6 1.340 and 1.348 corresponding together to 3 H)  
in addition to two multiplets ( 2  H each) centered at 6 5.58 and 7.04 exchan- 
geable with MeOD (NH2 groups). Manicoline B (2) was negative to ninhydrin 
reagent and therefore the exchangeable protons should be assigned to primary 
amide groups. 
The presence o CH2CONfIZ and CONH2 groups was supported by the EI 
216.1262 (CI3Hl6X2O 29%),  200.1084 (C13H14N0 ; 67.8%) ahd 172.1119 
(CI2H14N ; 16,5%) 
mass spectrum of peaks at m/z 217.3380 (C.  H N O ; l o o % ) ,  13 17 2 
can be attributed to ions (I) to (IV) respectively 
Scheme 1 
The 100.6 MHz "C n.m.r. spectrum of manicoline B (2) revealed two 
signals of equal intensity, having close chemical shifts, for most of the 
carbon resonances. This fact as well as the observed splitting of the 'H 
n . m . r .  signal due to the tertiary methyl group suggest that manicoline B 
(2) was an equimolecular mixture of two isomers. 
The complete structure of (2) was provided by single crystal X-ray 
analysis which showed unambigously that manicoline B was indeed a mixture 
of two diastereoisomers, epimeric at C-4. Attempts to separate the mixture 
failed and paucity of material prevented further investigation. 
X-ray analysis : The crystals grown from acetone displayed large 
mosaicity. A small p ate of (31, size 0 . 2 x ~ . 2 x O - O 5  mm, was mounted on 
an automatic four-ci cle diffractometer using graphite-monochromatized 
C u K a  radiation (A=1.5418 A). The system is triclinic, space group Pl 
with two molecules i the unit cell. The parameters are : a =  11.579 ( 4 1 ,  
b =  8.859 ( 3 1 ,  c =  8.779 l o  ( 3 )  Å, CL= 119.72 (81, ß =  83.22 ( 7 )  and Y =  101.80 
( 7 ) "  with a total volume of 765.4 Å 3 .  The reflections were recorded up to 
8=  600 in the 8/28 scanning mode. After Lorentz and polarisation correc- 
2361 
tions 2105 structural factors were considered as observed ( I > , 2 a ( I ) ) .  The 
analysis of the normalised structural factors clearly shows a centrosym- 
metric distributiox suggesting that the P? space group may be a possible 
alternative. However, this possibility is ruled out since manicoline B (2) 
is optically active. The structure was solved by direct methods3 in the Pl 
space group and refined with anisotropic thermal factors for heavy atoms to 
a final R =  9.7%. Hydrogen atoms were introduced at their theoretical places 
with an isotropic thermal factor equal to that of the bonded atom. The large 
discrepancies between the observed bond values for the amide groups suggest 
a rotation around C ( 2 )  - C ( 3 )  and C ( 1 )  - C ( 1 4 )  bonds. Different configurations 
were computed without bringing any clear distinction between the N and O 
atoms. The crystal structure is shown in the Figure'. The two molecules of 
the unit cell are in fact diastereoisomers which crystallize together and 
differ only by the configuration at C-4. Both diastereoisomers are linked 
together by hydrogen bonds, d [ 0 ( 2 )  ... N ( 2 ' ) ] = 2 . 9 1  A and dCO(2') ... N ( 2 ) ]  
=2.87 A ,  especially around the pseudo centre of symmetry responsible for the 
near centrosymmetric distribution of the E factors observed in the initial 
steps of the resolution. 
13 
FIGURE. Crystal structure of manicoline B (2) ; the hydrogen atoms 
except H-7 are omitted. The numbering is that of manicoline A (2). 
The biogenetic precursor of manicol (2) and manicoline A (2) was sup- 
1 
* posed to be an eudesmane type sesquiterpenoid'". It seems reasonable to 
assume that manicoline B (2) is formed from manicol in the manner shown in 
Scheme 2 .  
Acknowledgements : We are grateful to M r  P. Varenne for the high resolution 
mass spectrum and Dr B.C. Das for helpful discussions concerning the mass 
spectral fragmentation. 
2 3 6 2  
NH:, 
-H2N& 
Scheme 2 
REFERENCES AND NOTES 
1. J. Polonsky, J. Varenne, T. Prangé, C. Pascard, H. Jacguemin, and 
A. Fournet, J.C.S. Chem. C o m .  , 1981, 731. 
2 .  J. Polonsky, J.C. Beloeil, T. Prangé, C .  Pascard, H. Jacquemin, 
D.M.X. Domelly, P.T.M. Kenny, Tetrahedron, 1983, 2, 2655. 
3 .  G. Germain, P. Main, and M. Woolfson, Acta, Sect. A, 
1971, 3, 368-  
4. The atomic co-ordinates for this work are available from the Director 
of the Cambridge Crystallographic Data Centre, University Chemical 
Laboratory, Lensfield Road, Cambridge CB2 IEW. A n y  request should be 
accompanied by the full literature citation for this co-"mication. 
(Received in France 21 March 1984) 
i 
Reprinted from 
TETRAHEDRON LETTERS 
I 
l Vol. 25, NO. 2 2 , ~ ~ .  2359-2362 
i 
1 
i 
i 
\ J. POLONSKY,” T. PRANGÉ,* C. PASCARD,* H. JACQUEMIN? and A. FOURNET? 
*Institut de Chimie des Substances Naturelles, C.N.R.S. 91 190 Gif-sur-Yvette, France and ?Office de la Rebherche 
Scientifique et Technique, Outre-Mer, B.P. 165, Cayenne, Guyane, France 
STRUCTURE (X-RAY) ANALYSIS OF MANICOLINE B, 
A MIXTURE OF TWO DIASTEREOISOMERS OF A NEW 
ALKALOID FROM D ULA CIA G UIANENSIS (OLACACEAE) 
i 
PERGAMON PRESS 
OXFORD * NEWYORK * TORONTO - SYDNEY * PARIS FRANKFURT , 
1984 !g9 JRN. 1985 
Q. R. S.T.O. M, Fonds Df)u”ntaire 
No : J&44< ,  u A 


Structure (X-Ray) analysis of manicoline B, a mixture of two diastereoisomers of a new alkaloid from Dulacia guianensis (Olacaceae)

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