Phyfochemistry, Vol. 31,No. 1,pp.

317-319,1992 003l-9422/92
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DIMERIC ALKALOIDS FROM PSYCHOTRIA FORSTERIANA

YACOUB ADIIBADE, BERNARD WENIGER, JEAN C. QUIRION,*BERNARD KUBALLA, PIERRE CABALIoNt

and ROBERT ANTONS
Universit6 Louis Pasteur de Strasbour8 FacultC de Pharmacie, Laboratoire de Pharmacognosie, BP 24, F-67401 Illkirch cedex,
France; *Institut de Chimie des Substances Naturelles, CNRS, F-91198 Gif-sur-Yvette, France; tOrstom, 213 rue Lafayette, F-75010
Paris, France

(Received in revised form 5 June 1991)

Key Word Index-Psychotria forsteriana; Rubiaceae; alkaloids; calycanthine; iso-calycanthinc; meso-chimonan-

thine.

Abstract-Three alkaloids, (-)-calycanthine, iso-calycanthine and meso-chimonanthine, a dimeric indole isomeric

with the former compounds have been isolated from Psychotriaforsteriana and identified on the basis of their spectral
data and by comparison with those of previously described compounds.

INTRODUCTION which in turn could serve as the precursor of both la and

Polyindolinic alkaloids have been isolated from different lb and the remaining possible isomers c-e [4-71. On the
organs of Psychotriuforsteriuna (Rubiaceae). These com- basis of X-ray diffraction and spectroscopic data, the
pounds were mainly isomers of hodgkinsine, quadrige- structures la and lb were assigned respectively for (+ )-
mine Band psychotridine which are all polymers contain- calycanthine and (rac)-chimonanthine [4, 81. The three
ing three, four and five N(b)-methyltryptamine units, alkaloids displayed a typical PhNCN chromophore in
respectively [ 11. More peculiar was the occurrence in this their UV spectra and corresponded in M, (m/z 346) to
species of dimeric isomers of calycanthine, a tetrahydro- calycanthine isomers, Cz2Hz4N4.
The ‘%NMR spectra of (-)-calycanthine and iso-
quinoline alkaloid commonly regarded as the major
alkaloid of the genus Calycanthus order Calycanthaceae calycanthine showed only 11 signals indicating that both
[Z], and which had never been isolated before from alkaloids are dimeric in nature. The monomeric subunit
Psyckotria. These alkaloids were identified as (-)-
in the case of (-)-calycanthine would contain a N-methyl
calycanthine, as iso-calycanthine, one of the isomers of carbon appearing at 643.3, six carbons as a disubstituted
calycanthine isolated here for the first time from a natural
aromatic ring, a quaternary carbon appearing as a singlet
source, and as meso-chimonanthine, a dimeric indole
at 636.7, two methylene carbons at 632.5 and 47.3 and a
isomeric to the former compounds, on the basis of their
methane carbon between two nitrogens at 671.82. These
spectral data and by comparison of these data with those
values are quite similar for iso-calycanthine (see Experi-
mental). The ‘HNMR supported these assignments and
of previously described substances. Moreover, the signals
in the ‘HNMR spectrum of calycanthine have been
indicated an ortho-disubstituted aromatic ring. The pro-
attributed here precisely, on the basis of coupling con-
tons of the two methylene groups exhibited an AA-XX
pattern which is slightly modified in the case of iso-
stants analysis.
calycanthine. Whereas the ‘HNMR spectrum of (-)-
calycanthine showed an ABCD pattern at 66.64 (eight
aromatic protons), a singlet at 64.31 (R&H, 2H), and a
RESULTS AND DISCUSSION
broad singlet at 62.41 (N-Me; 6H), iso-calycanthine ex-
The quinoline dimeric tryptophane &rived bases are hibited slight modifications of the signals in the aromatic
commonly known as the major alkaloids of the order region. Stacking of the signals could be observed (super-
Calycanthaceae [Z]. Calycanthine (la) was first isolated in position of a td and ddat 67.02) with a slight deshielding
1888 and its correct formula Cz2Hz4N4 was derived only effect of these protons. In the upper fields, the signals are
in 1939 [3]. The postulate was independently made by also modified with the four methylenic protons appearing
Woodward [4] and Robinson [S] that calycanthine as complex signals. A comparison of the isolated alkal-
represented one of the feasible dehydrodimers of trypta- oids to authentic calycanthine confirmed the identity of
mine produced by coupling of a mesomeric tryptamine the first with calycanthine la. However, its optical rota-
radical, on the basis of its numerous degradation pro- tion ([algo -489”) was opposite in sign to that of calycan-
ducts, particularly N(b)-methylcalycanine and trypta- thine.
mine. The intermediate indolenine 2 could cyclise directly NMR studies allowed complete assignment of the
to one of the isomers lb (now known to be chimonan- signals in the ‘H and ‘“C NMR spectra (see Experimental
thine) or suffer hydrolysis to a tetra-aminodialdehyde and Fig. 1). Further bidimentiosal NMR studies (COSY,
XHCORR) were in favour of structure Id for iso-calycan-
thine. In the mass spectrum of calycanthine, the peak at
$Author to whom correspondence should be addressed. m/z 231 corresponds to protonated calycanine 3 and is

317
318 Y. ADJIBADEet al.
he
la
Me
I I
i ti I
Me
Id
the second peak in intensity after the parent ion. The
fragmentation of iso-calycanthine is also slightly different
compared to (-)-calycanthine; the peak at m/z 231 is not
very abundant. These date confirmed the structural ana-
logies of iso-calycanthine and (-)-calycanthine and are in
accordance with the proposed structure. Of the five
isomers (a-e) only b (chimonanthine) shows a completely
symmetrical fragmentation in the mass spectrum, yield-
ing two preponderant fragments m/z 172 (4) and m/z 130
(5). Thus, the third alkaloid could be assigned a chimon-
anthine-type structure according to its spectral data but it
is not optically active.
Implicit in the formulae a+ is a stereochemistry de-
pendent on the two ccntres generated in the production of
the dimer 2. Thus, each isomer may belong to a rat or
meso series. All of the alkaloids of the Calycanthars
isolated so far belong to the optically active series. But the
possibility of obtaining meso-compounds in vitro, as
reported by Hall et al. in their biogenetic type-synthesis of
calycanthaceous alkaloids [6], has considerable relev-
ance for the natural process. This has been confirmed by
isolation of rrreso-chimonanthine from Meratia praecox
(Rubiaceae) and now in the presently studied species. The
laevorotatory isomer of calycanthine was isolated for the
first time from Pausinystalia mucroceras, a species of the
tribe Cinchoneae, Rubiaceae [9]. It was also shown to
occur in skin extracts from the Colombian poison dart
frog Phyllobates terribilis (Dendrobatideae) [lo].
iso-Calycanthine Id is the third alkaloid among the five
feasible dimers of tryptamine being isolated here from a
natural source for the first time to our knowledge. The
phytochemical significance of the occurrence of such
dimeric alkaloids in species taxonomically distant from
lb
Me
tie
le
Calycanthus has been thoroughly discussed by Leboeuf et
al. and support the argument that they derive from a
simple biogenetic pathway [9]. The presence of meso-
chimonanthine could also explain that of (-)-
calycanthine (from a biogenetic point of view) by a
process analogous to the one through which isomeriza-
tion of dextrorotatory calycanthine yields laevorotatory
chimonanthine [7].
EXPERIMENTAL
General. Mps: uncorr. UV spectra were run in EtOH and IR
spectra in KBr discs. NMR spectra were recorded at 200 (‘H)
and 50 MHz (13C). Chemical shifts are given in 6 values with
CHCI, as int. std. All solvents were spectral grade or distilled
prior to use.
Plant material. P. forsteriana A. Gray was collected and
identified by Dr P. Cabalion in Vanuatu. A voucher specimen is
deposited in the ORSTOM Center Herbarium Noumea, New
Caledonia.
Zsolationof compounds. Plant organ extracts were obtained
using a classical acid-base extraction procedure. Alkaloids were
isolated by CC, mostly over Al,O,, eluted with mixts of
toluene-MeOH of increasing polarity and by further purifica-
tions on TLC, as reported in [ll]. The following compounds
were isolated, (-)-calycanthine (0.12% w/w dried stem bark;
0.0036% w/w dried fruits), iso-calycanthine (0.036% w/w dried
stem bark; 0.004% w/w dried fruits) and meso-chimonanthine
(0.0097% w/w dried fruits), and were recovered after
recrystallization from EtOH.
(-)-CaLycanthine. CZ2HZ4N4 (HRMS m/z talc. 346.2157;
found 346.2156). [a];‘: -489 (EtOH; ~9). Mp: 245”. UV
J.,,,,, nm: 250; 3 10. IR v,,, cn- I: 3570; 3400; 3350; 2900; 2800;
 Alkaloids from Psychotria forsteriana 319

Fig. 1. ‘HNMR coupling constants assignments of caly-

cantbine.

meso-Chimonanrhine. C2zHz4N4 (HRMS m/z talc. 346.2157;

found 346.2149). [alho: 0 (EtOH, c 1). Mp: 176”. UV 2::” nm:
3 m/z231 248; 303. IR vzi’ cm -I: 3450, 3oo0, 2940; 2880; 1650; 1525;
1500. MS (EI, 70 eV) m/z (tel. int.): 346 (13); 245 (12); 231(4); 174
(88); 173 (89k 172 (100); 171(75); 157 (16k 143 (17); 131(35); 130
(82); 117 (15); 103 (11). ‘HNMR (CDCl,): 1.26 (sk 2.07 (m); 2.40
(s); 2.55 (m); 2.83 (mk 6.50 d (J=8 Hz); 7.02 (m). i3CNMR
(CDCI,): 36.38; 53.06; 64.72; 83.99; 109.5; 119.18; 125.22, 128.91;
133.67; 152.5.

4 m/z172 5 m/z 130

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