Jacquemin, Henri

Polonsky, J.

Rabanal, R.M.

Varon, Z.

Horizon / Pleins textes

21,20-Anhydromelianone and Melianone from Simarouba amara 
(Simaroubaceae); Carbon-13 NMR Spectral Analysis of 
A’-Tirucallol-Type Triterpenes 
JUDITH POLONSKY, ZOIA VARON AND ROSA M. RABANAL 
Institut de Chimie des Substances Naturelles, CNRS, 91190 Gif sur Yvette, France 
AND 
HENRY JACQUEMIN 
Office de la Recherche Scientifique et Technique Outre-Mer, BP no 165, Cayenne, Guyane 
(Received 2 June 1977) 
Abstract. Further examination of the hexane extract of the root bark of Simarouba 
amara (Simaroubaceae) has led to the isolation of two side chain oxygenated A’- 
tirucallol-type triterpenes in addition to the already reported compounds 4 and S. One 
has been found to be identical with the known melianone 8 and the second is a new 
compound and has been shown to be 21,20-anhydromelianone 11. The 13C-NMR 
spectra of nine A’-tirucallol derivatives have been analysed and the data obtained have 
been applied to the confirmation of the structure of the new substance 11. 
INTRODUCTION z* 
*;zo 
The quassinoids’*’ and the limonoids (meliacin~)’.~ are 
groups of structurally complex highly oxygenated triter- 
pene degradation products. They occur in three very 
be considered as modified tertranortriterpenes are found 
in the Meliaceae and Rutaceae families, and the quas- 
sinoids which occur as further triterpene breakdown 
products (mostly decanortriterpenes) have been found so = Rr = CH, 4 R = 0  R’=CH3 
far only in the Simaroubaceae family. S R = 0  R‘=CHO 
The triterpenoid biogenetic pathway for the quas- R=(  OH R‘=CH,OH 6 R = O  R’=CH3 
27 
15 
10 closely related plant families. The limonoids which can 2 1  
R 4 5  
. 8  
ao ‘2) 
carboxy-26 sinoids has been experimentally verified using labelled -H 
mevalonate precursors.c6 Biosynthetic work on the 
limonoid nimbolide has also been r e p ~ r t e d . ~  As to the 
triterpenoid precursor of the limonoids and quassinoids, 
it is currently believed to be  a A’-tirucallol-type of 
triterpene which undergoes an apo-euphol rearrange- 
ment.’.’ This skeletal rearrangement, during which the 
CI4 methyl group migrates back to C ,  is supposed to 
proceed via the 7a,Sa-epoxide leading to a 7a-hydroxy- 
apotirucallol derivative.” 
rivatives, such as flindissol’, turraeanthin (7),’ melianone 
(S),” etc., believed intermediates on the biosynthetic , = <oHAc R, = (H OH 
route of the limonoids and quassinoids, have been iso- 
OH lated from the Meliaceae and Rutaceae families. Of 
particular biogenetic interest are two tirucalla-7-ene de- 
rivatives quite recently isolated by Halsall and Troke 
from Turraenthus africanus (meliaceae):I2 the 7 q S a  - 
epoxide of epiturraeanthin and a tirucallane triterpene in 
which the side chain has been degraded with the loss of 
four carbon atoms to a y-lactone and which has been 
found to be  identical with the lactone prepared an- 
teriorly’, from melianodiol (12). 
Only a few &triterPenes have so far been extracted 
from the Simaroubaceae family. Melianodiol (12) and 
its diacetate 13 have been isolated” from Sarnadera 
madagascariensis J. (synonymous with Samadera indica 
Gaertn.) and more recently the structure determination 
of oxo-3-tirucalla-7,24-diene (4) and dioxo-3,21-tirucalla- 
7,24-diene (5) from Simarouba amara Aubl. has been 
r e p ~ r t e d . ’ ~  
3 R = q OH R‘=CH, 
dihydro-24,25 
A number of side chain oxygenated A’-tirucallol de- R 
R E O  R’ = CH 
= Rt = o 
2 
/o\ 
17 
CH-CMez group. These spectral data are in good 
agreement with those observed for a similar epoxy group 
present in aplaio1.'6 turraeanthin (7)' and melianone @)." 
r - C. 
ion Y : CZaH3,O3 
13 R = O  
14 RE<*' 
OH R' = CH 
R? =OH 
H 
R" = Ac 
Further examination of the root back of Sirnarouba 
amara from Guyana has now proven the presence of two 
more A'-tirucallane-type triterpenes. One turned out to 
be identical with melianone (8), the major constituent of 
Melia azedarach (meliaceae), whose structure has been 
determined by Lavie and co-workers." The second is a 
new one for which we propose a structure 11 of anhyd- 
romelianone. 
The utility of "C-NMR spectroscopy for the purpose 
of structure elucidation of these oxygenated triterpenes 
of biogenetic interest is evident. Therefore a study and 
assignment of I3C-NMR shifts in this group of A'- 
tirucallol derivatives was undertaken and the data ob: 
tained have been applied to the confirmation of the 
structure of the new substance 11. 
20,Zl -Anhydromelianone 11 and Melianone 8 
The powdered root bark of S. amara was extracted by 
percolation with hexane and the extracts chromatog- 
raphed on silica columns. In this way we isolated, apart 
from sitosterol, A'-tirucallone (4) and 21-OXO-A'- 
tirucallone (5)  previously obtained from the stem bark, 
two crystalline compounds. 
Z0,Zl -Ankydromelianone (U). Crystals from 
methanol, mp 165-166", [a],-34.2" (c = 0.94; CHCI,). It 
has the formula C,H,O, (found: M' 452.3299; calcd 
452.3290). The triterpenoid nature of this compound is 
indicated by its 'H-NMR spectrum which displays seven 
quaternary methyl signals [at 0.78, 1.02, 1.07 (6H), 1.12, 
1.32 and 1.35 ppm]. The IR spectrum (nujol) which has 
no O H  bands, shows a band at 1700 cm-' for a six- 
membered ring ketone and the CD curve in dioxane shows 
a negative Cotton effect (he = 0.63 at 297 nm) of the 
same sign and magnitude as that of 3-keto-A'- 
triterpen~ids.".'~ 
The presence of the 24,25-epoxy group is indicated by 
the following: (a) Two of the methyl groups appear in the 
'H-NMR spectrum at chemical shifts (6 1.32 and 1.35 
ppm) which suggest that they are attached to a carbon 
atom bearing oxygen; (b) This NMR spectrum has a 
signal (doublet) at 2.91 ppm (J = 8 Hz) due to a proton of 
an epoxide ring; (c) A peak at m/e 381 having the 
fragment formula C26H3702 accounts for the loss of the 
The 'H-ÑMR spectrum (and ;he "C-NMR spectrum, 
see later) shows the presence of two double bonds, each 
carrying one vinyl proton. The chemical shift and the 
multiplicity of one of them (m at 6 5.36 ppm) agrees with 
the presence of a A7*' double bond.l4 
The dihydrofuran structure on the side chain as shown 
in 11, which accounts for the second double bond and for 
the third oxygen atom, was disclosed from the following 
arguments. The 'H-NMR spectrum of 11 shows a one 
proton signal at 6.12 ppm (d, 4J = 1.5 Hz) and a one 
proton multiplet centered at 4.35 ppm. These chemical 
shifts fit well for the Czl proton and the C, proton, 
respectively; the signal at 4.35 ppm was an ill-defined 
six-line pattern, the C, proton being coupled to the c 2 4  
proton and further split by the C22 methylene protons. 
Furthermore, the mass spectrum of 11 showed the base 
peak at m/e 166 having the fragment formula C10H1402 
(found: 166.0984; calc 166.0985), which can reasonably 
be assigned to the ion (X) arising by cleavage of the 
c13-c17 and bonds. 
An attempt to correlate compound 11 to turraeanthin 
7 by treatment of the latter with mesyl chloride in 
pyridine failed. But refluxing turraeanthinglycol (14y 
with acetic anhydride in presence of sodium acetate led, 
in 25% yield, to the non-previously described compound 
10: Crystals from methanol, mp 13$-136", [m]D-17" (c = 
1.19 CHCl,), C36H4107 (M' 598).* It's IR spectrum had 
no O H  band and its 'H-NMR spectrum shows signals for 
the c 2 6  and Cn methyl groups at 1.63 and 1.53 ppm, for 
three acetoxy-groups (6 1.96,2.07 and 2.15 ppm) and €or 
two single protons at 6 5.26 ppm (FI7) and at 6.0 ppm (d, 
'J = 0.6Hz). The latter signal is assigned to the C,, proton 
as shown by it ',C-NMR spectrum (Table 1) which 
displays four olefinic sp2 carbon atoms: C7 (d, 118.0 ppm), 
C8 (s, 145.5 ppm), C,, (s, 115.4 ppm) and Czl (d, 140.2 
Lack of material has prevented the conversion of 
21,20-anhydromelianone to compound 10, but its struc- 
ture is fully confirmed by its ',C-NMR spectrum and 
particularly by comparison with that of compound 10. 
Melianone (8).  The more polar compound crystallised 
from chloroform-pentane, mp 212-214", [aID-48" (c = 
0.97; CHCI,). It has the formula C3H4604 (found: M' 
470.3415; calcd 470.3396). Its IR spectrum, which showed 
an O H  band and a carbmyl band (1700 cm-'), and its 
'H-NMR spectrum indicated this compound to be 
melianone (S)." Oxidation with chromium trioxide- 
pyridine gave the y-lactone 9, C,H,04 (M'. 468), mp 
197-199", [a]D-71.5" (c = 0.92; CHCI,), with infrared 
bands at 1700 and 1775 cm-', thus proving the presence 
of the five-membered cyclic hemiacetal structure. The 
'H-NMR spectrum (60 MHz) of compound 8 displays a 
set of signals between 0.85 and 1.34 ppm which can be 
related to seven methyl groups: A doublet (1 H)  at 2.9 
ppm (J = 8 Hz) for the epoxide proton (24-H), a multiplet 
(1 H) centered at 3.95 ppm for the C, proton, and a non 
resolved triplet (2 H) at 5.38 ppm for the C7 and C,, 
protons. The 'H-NMR spectrum (90 MHz) of the lactone 
9 shows seven distinct methyl signals (6 0.83, 102,  1.04, 
1.07, 1.12, 1.35 and 1.37 ppm) and three one proton 
signals, a doublet at 2.81 (J = 7.6 Hz) and multiplets at 
P P 4 .  
* Chemical ionization mass spectrum shows a quasi molecu- 
lar peak MH' at mle 599. 
Poloiisky et al. / Tirucallol-type Triterpenes 
18 
Table 1. Carbon Chemical Shifts 
Carbon 
number 1 2 3 4 5 6 7 8 9 10 11 
1 37.1 
2 27.6 
3 79.0 
4 38.8 
5 50.5 
6 23.9 
7 117.3 
8 145.3 
9 48.9 
10 35.8 
11 27.2 
12 34.0 
13 43.4 
14 51.0 
15 33.8 
16 28.1 
17 52.8 
18 13.1 
19 18.1 
20 . 36.1 
21 18.1 
22 36.1 
23 25.0 
24 124.7 
25 130.3 
26 25.6 
27 17.6 
28 21.8 
29 27.6 
30 14.3 
37.2 
27.6 
78.9 
38.8 
50.5 
23.8 
117.6 
145.0 
48.7 
34.8 
27.3 
33.9 
43.2 
51.0 
32.8 
24.8 
46.9 
13.1 
17.7 
42.5 
62.3 
29.5 
25.6 
124.5 
130.8 
25.6 
17.7 
22.0 
27.6 
14.7 
37.1 
27.6 
78.8 
38.8 
50.5 
24.1 
117.3 
145.3 
48.8 
34.8 
27.6 
33.9 
43.3 
50.9 
33.9 
27.6 
52.8 
13.1 
18.0 
36.0 
18.0 
36.0 
24.9 
39.3 
27.6 
22.5 
22.5 
21.5 
27.6 
14.6 
38.4 
34.9 
216.6 
47.8 
52.3 
24.4 
117.7 
146.0 
48.2 
34.9 
27.3 
34.0 
43.5 
51.1 
33.6 
28.2 
52.9 
12.7 
18.3 
35.8 
18.3 
36.1 
24.9 
125.1 
130.8 
25.6 
17.5 
21.5 
24.4 
21.5 
38.2 
34.7 
215.4 
47.6 
52.1 
24.7 
117.8 
144.6 
48.2 
34.9 
26.9 
31.9 
43.2 
50.7 
33.6 
29.1 
48.2 
12.7 
17.7 
55.0 
204.7 
29.6 
25.8 
123.1 
131.9 
25.5 
17.7 
22.8 
24.3 
21.5 
38.3 
34.7 
216.6 
47.6 
52.1 
24.3" 
117.6 
145.7 
48.3 
34.7 
27.3 
33.4 
43.4 
50.9 
32.8 
27.9 
52.5 
36.7 
23.8 
81.0 
37.7 
50.7 
23.2 
117.8 
r45.7 { 145.5 
34.8 
.27.4 
35.1 
43.5 
50.4 
34.2, 
31.5 
12.6 13.0 
18.3 17.5 
35.8 33.7 
18.3 (':;:: 
35.4 24.9 
78.3 
26'9" (77.1 
67.8 
125'9 f65.4 
146.6 
173.0 
20.3 
21.3 
24.3 
21.4 
, -
57.8 
[57.1 
24.1" 
19.2" 
22.5 
27.4 
15.8 
38.5 
35.0 
216.8 
47.8 
52.4 
24.4 
118.0 
145.6 
48.3 
34.9 
27.4 
35.1" 
43.5 
50.4 
34.2" 
31.5" 
(49.5 
12.7 
17.7 
33.8 
101.7 
97.7 
24.9 
57.9 
(57.2 
24.9" 
19.2" 
22.5 
24.4 
21.5 
38.5 36.8 
35.1 23.8 
216.7 81.0 
47.8 37.8 
52.4 50.8 
24.4 23.8 
118.2 118.0 
145.3 145.5 
48.4 48.8 
34.9 34.9 
27.4 27.4 
33.8" 36.8 
43.7 44.1 
50.5 50.3 
31.0" 34.3 
30.0" 31.9 
47.1 45.4 
12.7 13.1 
17.6 17.5 
40.4 115.4 
177.6 140.2 
23.5 25.2 
77.9 76.6 
64.5 78.5 
57.2 82.9 
23.5" 24.2" 
19.4" 22.9" 
23.0 22.9 
24.4 27.4 
21.5 15.8 
38.5 
35.1 
216.5 
47.8 
52.3 
24.4 
118.1 
145.4 
48.4 
34.9 
27.4 
36.2 ' 
44.1 -. 
50.2 
34.3 . 
31.9 
45.3 
12.7 
17.7 
114.0 
140.0 
24.9 
80.9 
l. 
65.7 
57.2 
25.3" 
19.3" 
22.0 
24.4 
21.5 
a. Values within any vertical column may be reversed. In compound 7: CH,CO at 171.05 ppm; CH,CO at 21.5 ppm. In 
compound 10: CH,CO at 170.9; 170.6 and 170.1 ppm; CH,CO: 22.4; 21.3; 21.0 ppm. 
4.16 and 5.30 ppm, due to the C,, C, and C, protons, 
respectively. The assignment of the signals to CZ4 and C, 
protons was demonstrated by a spin decoupling experi- 
ment. 
Final proof of the structure 8 was obtained by direct 
comparison with authentic melianone from Melia 
atedarach ' I  (identity of MS, 'H and I3C-NMR spectra). 
The "C-NMR spectrum of melianone (see below) 
shows clearly that it exists in solution like turreaenthin 
(7); as a CZ1 epimeric mixture. This may explain the 
discrepancy of the mp and [alD we observed and those 
quoted in Refs. 7 and 9. 
As to the fragmentation pattern of melianone by mass 
spectroscopy, its high resolution mass spectrum does not 
show any peak at m/e 71 reported to arise by cleavage 
of the Cz4-C, bond but rather shows a weak peak at m/e 
399 (11.2%) corresponding to the composition C&&2, 
(M+-71). The base peak is observed at m/e 383.2586 
having the fragment formula CUH3,03 which can be 
assigned to the ion (Y). Other significant peaks are found 
at m/e 437 (83%) C29H4103 (M+-Me-H,O), m/e 365 
(70.4%) C&& (ion Y-H,O) and at m/e 297 (46%) 
CZ1HZ90 (ion Y-C,H,O,). 
Israel Journal of Chemistry 16 1977 
Carbon-13 NMR Analysis of Compounds 1 to 11 
Noise and single frequency decoupled 13C-NMR 
spectra were recorded* for compounds 1 to 11 and the 
chemical shift assignments are indicated in Table 1. The 
carbon resonances in these compounds were assigned on 
the basis of the residual splitting in off-resonance de- 
coupled spectra, data of the previously published mod- 
els,'%'' and comparison with the spectra of structurally 
related compounds. The structure determination of com- 
pounds 4 and 5 and the preparation of their derivatives 1, 
2 and 3 have been reported previo~s ly ; '~  the 13C-NMR 
spectrum of terebinthone (6) was obtained by courtesy of 
Professor E. Wenkert and Dr. J. de Paiva de Campello. 
The chemical shift assignment for compounds 1 to 9 is 
straightforward and does not require any special com- 
ment. The Cz and CIO resonances in compound 4 are 
found at 34.9 ppm as a signal which appears as a triplet 
(overlapped by a singlet) in the off -resonance decoupled 
- 
c 
* ',C-NMR spectra were recorded in CDCI, solution on a 
Bruker HX-90E F.T. NMR spectrometer operating at 22.63 
MHz. Chemical shifts are given in ppm with respect to internal 
TMS. 
spectrum (sford), whereas, it is found as a singlet due to 
the CIO carbon in the sford spectrum of the 2- 
dideuterated derivative. Inspection of the chemical shifts 
for the side chain carbons of the presently reported 
compounds 1-6 and for the previously described euphol" 
indicates that the stereochemistry cannot be  deduced 
from "C-NMR spectroscopy. The chemical shifts for the 
two series of substances are identical within the experi- 
mental error as far as the Ci7 side chain carbons are 
concerned. 
The proposed Cl, side chain of our new compound 11 
is in good agreement with the observed chemical shifts. 
The 6-values of 65.7 (d) and 57.2 (s) ppm reflect respec- 
tively the presence of a neopentylic epoxymethine and a 
quaternary epoxy carbon; they are also found in tur- 
r,eaenthin (7) and melianone (8) which possess the c24-c25 
epoxide ring. This is further confirmed by the shift 
contrast between 11 and 10, since in the spectrum of the 
latter compound Cz4 and Cu appear at 78.5 and 83.9 ppm. 
The C, resonance in compound 11 appears at 80.9 ppm 
(d), which is shifted to about 2 ppm highfield in tur- 
reaenthin and melianone. 
The spectrum of compound 11 clearly shows one 
carbonyl (s at 216.5 ppm) and four olefinic sp2 carbon 
atoms: C7 (d, 118.1 ppm), C8 (s, 145.4 ppm), C, (s, 114.0 
ppm) and Czl (d, 140.0 ppm). 
Inspection of the I3C spectra of turreaenthin (7) and 
melianone (8) reveals that these compounds are epimeric 
mixtures at Czl. Actually, these spectra reveal two signals 
for the Czl carbon atom while there is only one present 
for Cal in the spectra of the compounds 9, 10 and 11 , 
which do not possess the hemiacetal structure. As a 
result of the epimeric mixture examined, important 
differences can be noticed for the, carbon signals which 
are in the vicinity of CZ1. Concerning turreaenthin, 
Halsall and coworkersg had reported that turreaenthin 
gives rise to an equilibrium mixture of the two possible 
hemiacetal structures, (the hemiacetal hydroxyl group 
being cis or trans to the four-carbon unit carrying the 
epoxy-group) and that this affects the chemical shift of 
the c 2 4  proton. It is of interest to note that some carbons 
far from the CZl site also show closely spaced double 
signals as a consequence of subtle conformational effects. 
The structure of 21-20 anhydromelianone (11) is thus 
confirmed by the various 13C-NMR spectra examined 
during this investigation and particularly by the near 
identity of the chemical shifts of all the carbon atoms 
except those involved in, o r  in the immediate environ- 
ment of, the epoxide and ketone of 11 and the acetoxy 
groups of 10. 
"C-NMR analysis of the quassinoidsz2 and limonoidsz 
have been recently published. 
. 
19 
Acknowledgement. We are greatly indebted to Professor M. G. 
Halsall for samples of turreaenthin and turreaenthin-diol and to 
Professor D. Lavie for a sample of melianone. We wish to thank 
Mr. C. Marazano for high resolution mass measurements, Mr. P. 
Varenne for chemical ionisation mass spectrum, Mrs. C. Fon- 
taine and Mr. B. Septe for recording the NMR spectra and Dr. 
G. Lukacs for his help in their interpretation. 
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Polonsky et al. /Tirucallol-type Triterpenes 


21, 20-Anhydromelianone and Melianone from Simarouba amara (Simaroubaceae); Carbon-13 NMR Spectral Analysis of 7-Tirucallol-Type Triterpenes

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