Jafrine, a novel and labile β-carboline alkaloid from the flowers of Tagetes patula

Article abstract of DOI:10.1016/S0040-4020(02)00615-4

An inherently unstable and structurally novel tetrahydro β-carboline alkaloid, (+) jafrine (1) was isolated from the petroleum ether extract of Tagetes patula flowers. Its structure and stereochemistry has been determined with the help of spectroscopic analysis and the synthesis of racemate, (±) jafrine starting from available (±) tetrahydroharmine (2). The effect of solvent polarity on the ratio of amide rotamers of jafrine during NMR studies is discussed. The transformation of jafrine as well as 4-N-acetyl tetrahydroharmine (3), into 2-acetyl tryptamine derivatives by auto-oxidation was observed and its detail is presented. This process may be used as a synthetic tool for the preparation of tryptamine derivatives.

Full text of DOI:10.1016/S0040-4020(02)00615-4

TETRAHEDRON
Pergamon
Tetrahedron 58 (2002) 6185±6197
Jafrine, a novel and labile b-carboline alkaloid from the ¯owers of
Tagetes patulaq
Shaheen Faizip and Aneela Naz
H.E.J. Research Institute of Chemistry, University of Karachi, Karachi 75270, Pakistan
Dedicated to the fond memory of Professor Salim-uz-Zaman Siddiqui FRS (1897±1994), the founder director of H.E.J. Research Institute of Chemistry,
University of Karachi
Received 25 January 2002; revised 21 May 2002; accepted 13 June 2002
AbstractÐAn inherently unstable and structurally novel tetrahydro b-carboline alkaloid, (1) jafrine (1) was isolated from the petroleum
ether extract of Tagetes patula ¯owers. Its structure and stereochemistry has been determined with the help of spectroscopic analysis and the
synthesis of racemate, (^) jafrine starting from available (^) tetrahydroharmine (2). The effect of solvent polarity on the ratio of amide
rotamers of jafrine during NMR studies is discussed. The transformation of jafrine as well as 4-N-acetyl tetrahydroharmine (3), into 2-acetyl
tryptamine derivatives by auto-oxidation was observed and its detail is presented. This process may be used as a synthetic tool for the
preparation of tryptamine derivatives. q 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
2. Results and discussion
Tagetes patula Linn. (French Marigold) locally known as
Jafri, belongs to the family Asteraceae (Compositae). It is a
bushy annual, native to Mexico and other warmer parts of
America and naturalized elsewhere in the tropics and sub-
tropics. It is a small ornamental garden plant with multiple
uses.1 The ¯owers are employed for the treatment of
jaundice and hepatitis, while the whole plant is used for
the treatment of cough and dysentery. The roots and seeds
are used as purgative. Moreover, a cardiovascular drug was
formed from lyophilized powder of T. patula. The volatiles
from T. patula are highly effective toward both larvae and
adult mosquitoes. The roots contain nematocidal poly-
thienyls, including a little terthienyl.1 Phytochemical
investigation on its different parts has resulted in the iso-
lation of various chemical constituents such as thiophenes,
¯avonoids, benzofurans and carotenoids.2 The present paper
describes the isolation and structure elucidation of a novel
b-carboline alkaloid, jafrine (1) having a carbon substituent
at A ring, from T. patula. It is noteworthy that this type of
b-carboline is very rare3,4 and only one such compound had
previously been isolated from natural sources.3
The petroleum ether extract of red ¯owers of T. patula
yielded a tetrahydro b-carboline alkaloid, jafrine through
solvent separation followed by preparative thin layer
chromatography. The EI mass spectrum of jafrine (yellow
gum, [a]D ˆ119.23) showed a molecular ion peak at m/z
26
356.2078 consistent with the molecular formula
C21H28N2O3, which was supported by positive ion
(M111, m/z 357) and negative ion (M121, m/z 355) FAB
mass spectra. The IR spectrum displayed peaks at 3301
(hydrogen bonded N±H, very weak absorption), 3050
(aromatic C±H), 2952, 2855 (aliphatic C±H), 1682
(aromatic ketone), 1662 (tertiary amide carbonyl), 1621,
891 (aromatic ring), 1445 (CH2), and 1165 (C±O), while
its UV spectrum showed maxima at 300, 283, 253, and
210 nm indicating the presence of b-carboline skeleton.5a,b
The 1H NMR spectrum (CDCl3, Table 1) of jafrine
displayed two aromatic proton singlets at d 7.82 (1H,
H-9) and 6.81 (1H, H-12) and a methoxy group singlet at
3.86 (3H, 11-OCH3) revealing that the A ring of b-carboline
has the usual methoxy group at C-11 along with an electron
withdrawing substituent at C-10.5a,c That this substituent is a
caproyl group was shown by a set of resonances of methyl-
0
ene protons at d 2.98 (H-20), 1.67(H-3 ), 1.303 (H-40), and
1.28 (H-50) and methyl protons at 0.87(H-6 ). Moreover,
q Presented as a poster in the 7th Eurasia Conference on Chemical
Sciences, held at H.E.J. Research Institute of Chemistry, March 8±12,
2002, Karachi, Pakistan.
1
the H NMR data disclosed that C ring of b-carboline is
saturated6 and contained an acetyl group on its nitrogen.
The down-®eld chemical shift of indolic N±H showed its
intramolecular hydrogen bonding with the carbonyl func-
tion at 4-N(amide group), as in tetrahydroharmine (2) it
resonated at d 7.69 (CDCl3, Table 2), while in 4-N-acetyl
Keywords: tetrahydro b-carbolines; amide; Z/E rotamers; auto-oxidation.
Corresponding author. Tel.: 192-43128; fax: 192-21-9243190-91;
e-mail: shaheen@khi.comsats.net.pk
p
0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)00615-4

Table 1. 1H NMR data (ppm) for jafrine (1a11b), in different solvents at 500 MHz; coupling constants (J, Hz) are in parentheses
Proton
C6D6 (Z/E; 31.0:1.0)
1a (Z)
CDCl3 (Z/E; 6.0:1.0)
C3D6O (Z/E; 3.0:1.0)
CD3OD (Z/E; 3.2:1.0)
1a (Z) 1b (E)
1b (E)
1a (Z)
8.88a br.s
5.73 br.q (6.7)
3.97ddd (4.4, 6.3, 13.9)
3.45 ddd (6.2, 9.8, 13.9)
2.76 m
1b (E)
1a (Z)
10.18a br.s
1b (E)
10.15a br.s
1
3
5a
5b
6
8.50a br.s
8.45a br.s
5.03 m
5.01 m
2.51 m
2.15 m
8.48a br.s
4.94 br.q (6.6)
4.91 m
2.92 m
2.72 m
±
±
5.10 br.q (7.0)
N.O.
2.99 m
2.74±2.93 m
7.75 s
5.86 q (6.7)
3.11 dd (4.5, 13.5)
2.81 ddd (3.9, 10.8, 13.6)
2.20 m
5.66 br.q (6.6)
4.11 ddd (4.4, 6.5, 13.9)
3.46 ddd (5.3, 10.6, 14.0)
2.77 m
5.12 br.q (6.7)
4.84 br.dd (4.4, 12.8)
2.90 m
2.77 m
7.75 s
5.60 br.q (7.0)
4.10 ddd (2.0, 6.5, 14.0)
3.49 ddd (5.5, 11.0, 14.0)
2.74±2.93 m
7.75 s
b
9
12
8.38 s
6.65 s
8.22 s
6.46 s
7.82 s
6.81 s
7.82 s
6.76 s
7.73 s
6.98 s
2.92 m
1.64 m
1.31 m
1.27m
0.87 t (7.0)
3.90 s
2.14 s
6.99 s
2.92 m
1.64 m
1.31 m
1.27m
0.87 t (7.0)
3.90 s
2.13 s
6.92 s
6.93 s
20
3.20 t (7.4)
1.94 qn (7.3)
1.40 m
3.20 t (7.4)
1.94 qn (7.3)
1.40 m
2.98 t (7.5)
1.67 qn (7.5)
1.33 m
2.98 t (7.5)
1.67 qn (7.5)
1.33 m
2.99 t (7.0)
1.65 m
1.32 m
2.99 t (7.0)
1.65 m
1.32 m
30
40
50
1.30 m
1.30 m
1.28 m
1.28 m
1.27m
1.27m
60
0.87 t (7.1)
3.44 s
1.73 s
0.87 t (7.1)
3.44 s
1.82 s
0.87 t (7.0)
3.86 s
2.22 s
0.87 t (7.0)
3.81 s
2.14 s
0.88 t (7.0)
3.90 s
2.21 s
0.88 t (7.0)
3.90 s
2.16 s
11-OCH3
4-NCOCH3
3-CH3
1.31 d (6.7)
1.38 d (6.7)
1.42 d (6.7)
1.52 d (6.7)
1.41 d (6.7)
1.57 d (6.6)
1.45 d (7.0)
1.57 d (7.0)
a
Exchangeable with D2O.
N.O.ˆNot observed (hidden behind the water peak at d 4.8).
b

Table 2. 1H NMR data (ppm) for compounds 2, 6a, 6b, 7a, 7b, 8a and 8b in CDCl3 at 500 MHz; coupling constants (J, Hz) are in parentheses
Proton
2
(Z/E; 1.0:1.4)
(Z/E; 5.4:1.0)
(Z/E; 3.3:1.0)
6a (Z)
6b (E)
7a (Z)
7b (E)
8a (Z)
8b (E)
N.O.b
5.02 m
±
2.98 m
4.99 m
2.65 m
2.65 m
7.60 d (8.5)
6.78 d (8.5)
±
3.97s
±
2.14 s
1.52 d (7.0)
±
1
3
4
5a
7.69a br.s
4.13 tq (1.9, 6.7)
±
±
5.68 br.q (6.5)
±
4.88 br.dd (5.5, 13.8)
2.99 ddd (5.0, 11.3, 14.7)
2.74 m
2.74 m
7.33 d (8.5)
6.90 dd (2.0, 8.5)
7.18 d (2.5)
3.87s
8.69a br.s
5.71 br.q (6.6)
±
3.97ddd (3.7, 5.1, 13.9)
3.45 ddd (4.4, 11.7, 13.9)
8.36a br.s
4.96 br.q (6.5)
±
4.92 br.dd (4.9, 13.8)
2.93 ddd (4.3, 11.6, 13.8)
8.75a br.s
5.75 br.q (6.5)
±
6.35 br.q (7.0)
±
3.93 m
3.50 m
2.63 m
2.63 m
7.28 d (8.5)
6.82 dd (2.0, 8.5)
7.35 d (2.5)
3.86 s
2.74 s
2.18 s
1.64a br.s
3.33 ddd (3.5, 5.2, 12.9)
3.95 m
3.51 m
2.61±2.76 m
2.61±2.76 m
7.56 d (8.5)
6.77 d (8.5)
±
3.96 s
±
2.19 s
5b
6a
3.01 ddd (5.0, 9.0, 12.9)
2.71 dddd (1.9, 5.2, 9.0, 15.4)
2.77 m
2.77 m
7.93 s
±
6.82 s
3.88 s
±
2.72 m
2.72 m
7.93 s
±
6.74 s
3.82 s
±
6b
9
10
2.66 dddd (1.9, 3.5, 5.0, 15.4)
7.32 d (8.5)
6.74 dd (2.2, 8.5)
6.81 d (2.2)
12
11-OCH3
1-NAC
4-NAC
3-CH3
10- COCH3
12-COCH3
3.80 s
±
±
1.41 d (6.7)
±
±
2.77 s
2.20 s
2.21 s
1.43 d (7.0)
2.72 s
±
2.15 s
1.52 d (7.0)
2.72 s
±
1.44 d (6.5)
±
1.51 d (6.0)
±
1.46 d (7.0)
±
2.70 s
±
±
2.71 s
a
Exchangeable with D2O.
N.O.ˆNot observed.
b

Table 3. 1H NMR data (ppm) of 3 (3a13b) in CDCl3, C3D6O and CDCl31CD3OD at 500 MHz; coupling constants (J, Hz) are in parentheses
Proton
CDCl3 (Z/E;4.8:1.0)
C3D6O (Z/E; 2.8:1.0)
CDCl31CD3OD (1:1) (Z/E; 2.6:1.0)
3a (Z) 3b (E)
3a (Z)
3b (E)
3a (Z)
3b (E)
9.80a br.s
1
7.87a br.s
7.68a br.s
9.85a br.s
±
±
3
5a
5b
6a
5.71 br.q (6.5)
3.97ddd (3.5, 5.0, 14.0)
3.45 ddd (4.5, 11.5, 14.0)
2.76 m
4.97 br.q (6.5)
4.92 br.dd (5.0, 14.0)
2.93 ddd (4.5, 11.5, 14.0)
2.71 m
5.65 br.q (6.6)
4.07ddd (1.1, 4.9, 13.7)
3.44 ddd (4.3, 11.6, 13.7)
2.72 m
5.09 br.q (6.6)
4.82 ddd (1.3, 4.8, 12.9)
2.92 dt (4.4, 12.4, 12.4)
2.72 m
5.57 br.q (6.7)
3.96 ddd (3.4, 6.1, 14.0)
3.44 ddd (6.0, 10.1, 13.9)
2.74 m
4.98 br.q (6.6)
4.80 ddd (3.3, 6.1, 14.0)
2.95 ddd (6.0, 10.1, 13.9)
2.67 m
6b
9
10
2.76 m
7.32 d (8.5)
6.75 dd (2.0, 8.5)
6.83 d (2.0)
3.82 s
2.71 m
2.72 m
7.26 d (8.5)
6.66 dd (2.2, 8.5)
6.86 d (2.2)
3.76 s
2.72 m
7.28 d (8.5)
6.67 dd (2.2, 8.5)
6.84 d (2.2)
3.76 s
2.74 m
2.67 m
7.34 d (8.5)
6.77 dd (2.0, 8.5)
6.82 d (2.0)
3.84 s
2.18 s
1.54 d (6.5)
7.25 d (8.5)
6.67 dd (2.2, 8.5)
6.83 d (2.2)
3.78 s
2.16 s
1.41 d (6.7)
7.27 d (8.5)
6.68 dd (2.2, 8.5)
6.83 d (2.2)
3.78 s
2.16 s
1.52 d (6.6)
12
11-OCH3
4-NAC
3-CH3
2.19 s
1.43 d (6.5)
2.12 s
1.39 d (6.6)
2.12 s
1.55 d (6.6)
a
Exchangeable with D2O.

Table 4. 1H NMR data (ppm) of 3 (3a13b) in CD3OD, C5D5N, and C2D6SO at 500 MHz; coupling constants (J, Hz) are in parentheses
Proton
CD3OD (Z/E; 2.5:1.0)
C5D5N (Z/E; 3.4:1.0)
C2D6SO (Z/E; 2.8:1.0)
3a (Z)
3b (E)
3a (Z)
3b (E)
11.58a br.s
5. 13 br.q (7.0)
5.17br.dd (5.0, 13.0)
2.95 br.dt (4.0, 12.0, 12.0)
2.80 m
3a (Z)
10.55a br.s
5.44 q (6.5)
3.95 td (3.0, 3.0, 14.1)
3.31 td (6.8, 6.8, 14.0)
2.63 m
3b (E)
1
3
5a
5b
6a
6b
9
10
12
±
±
11.72a br.s
6.08 br.q (7.0)
3.88 ddd (1.5, 5.0, 13.5)
3.34 ddd (4.0, 11.5, 13.5)
2.73 dddd (1.0, 5.0, 11.0, 15.0)
2.67 dddd (1.5, 4.5, 5.0, 15.0)
7.53 d (8.5)
10.50a br.s
5. 01 br.q (6.5)
4.58 br.dd (3.1, 11.0)
2.89 dt (3.4, 10.9, 10.9)
2.63 m
5.60 q (6.5)
4.08 ddd (1.5, 5.0, 14.0)
3.48 ddd (5.0, 11.5, 14.0)
2.76 m
5.09 q (6.5)
N.O.b
3.02 ddd (6.5, 10.0, 13.0)
2.65 m
2.65 m
7.25 d (8.5)
6.75 dd (2.5, 8.5)
6.83 d (2.5)
3.78 s
2.76 m
2.74 m
2.63 m
2.63 m
7.24 d (8.5)
6.64 dd (2.0, 8.5)
6.82 d (2.0)
3.78 s
7.52 d (8.5)
7.03 dd (2.0, 8.5)
7.15 d (2.0)
3.72 s
7.24 d (8.5)
6.59 dd (2.0, 8.5)
6.82 d (2.0)
3.68 s
7.25 d (8.5)
6.60 dd (2.0, 8.5)
6.83 d (2.0)
3.68 s
7.04 dd (2.0, 8.5)
7.16 d (2.0)
3.73 s
11-OCH3
4-NAC
3-CH3
2.20 s
1.44 d (6.5)
2.16 s
1.57 d (6.5)
2.17s
1.52 d (7.0)
2.14 s
1.49 d (7.0)
2.07s
1.31 d (6.5)
2.08 s
1.43 d (6.5)
a
Exchangeable with D2O.
N.O.ˆNot observed (hidden behind the water peak at d 4.8).
b

6190
S. Faizi, A. Naz / Tetrahedron 58 (2002) 6185±6197
Table 5. 13C NMR data (ppm) of 1 (1a11b) and 3 (3a13b) in CDCl3 and CDCl31CD3OD (1:1) respectively at 300 MHz
(1)
(3)
Carbons
Syn (1a) (Z) (major)
Anti (1b) (E) (minor)
Syn (3a) (Z) (major)
Anti (3b) (E) (minor)
2
3
5
6
135.42
45.20
40.76
133.89
49.42
35.45
135.31
47.05
42.39
22.45
134.26
51.27
37.27
22.06
21.1723.33
7108.38
8
9
110.89
122.90
120.97N.O.
120.78
155.94
93.71
139.53
203.68
43.77
24.72
31.82
22.82
14.05
19.03
.64
N.O.
107
109.16
122.45
119.86
109.95
157.39
96.56
138.53
±
±
±
±
±
123.98
119.58
10
11
12
13
10
N.O.
N.O.
N.O.
N.O.
N.O.
N.O.
N.O.
N.O.
N.O.
N.O.
111.45
157.53
96.04
138.66
±
±
±
±
±
20
30
40
50
60
±
±
14
15
16
17
20.28
19.94
171.48
22.81
56.97
21.11
172.65
22.48
56.74
169.41
22.08
55.78
171.72
21.71
N.O.
N.O.ˆNot observed.
tetrahydroharmine (3) (Tables 3 and 4) it shifted down-®eld
to d 7.87 (CDCl3). The same trend in chemical shifts has
been observed for tetrahydroharmane derivatives.5b Out of
the nine degrees of unsaturation in the molecule, implied by
the molecular formula, seven have been accounted for by
tetrahydro b-carboline nucleus and two by carbonyl func-
tions. These structural features of jafrine were con®rmed
through extensive studies of 13C (Broad Band and DEPT,
Table 5) and 2D NMR spectra (COSY 458, HMQC and
HMBC). The 1H 1H COSY 458 spectrum showed
connectivities of both the spin systems of ring C and caproyl
moiety, present in the molecule. In the HMBC spectrum,
amide function, which produced the rotamers Z (syn) and
E (anti) in 1.8,9 It is noteworthy that, cyclic 4-N amide of
b-carbolines, strictosamide and congeners which could not
exist in isomeric forms due to the presence of torsional ring
strain, have exactly the same chemical shift values6,10 for
H-3, H-5a and H-5b as observed for rotamer 1b of 1.
The 13C NMR spectrum of 1 (Table 5) also showed the syn,
anti rotational isomerism in an excellent manner and gave
similar results which have been cited in literature for
different types of amides.9 As reported earlier, carbon
nuclei, cis to the carbonyl function, become more shielded
due to the positive magnetic anisotropy, thus, appear up-
®eld.9 In the case of 1, signi®cant 13C chemical shift
differences were observed between the syn and anti
3
important J bond connectivities were observed for C-2
(135.42) with H-6; C-7(108.38) with H-5a and H-9; C-8
(122.90) with H-12; C-10 (120.78) with H-12; and C-11
(155.94) with H-9 and H-17. Furthermore, the aromatic car-
bonyl at d 203.68 and the amide carbonyl at 169.41 showed
2J bond correlations with H-20 and H-16 respectively in the
HMBC spectrum.
13
rotamers (d 13C syn2d C anti) for C-3 (a), C-5 (a0), C-
2 (b), C-6 (b0), C-14 and other carbon nuclei (Fig. 1) nearest
to the range of magnetic anisotropy as depicted in Table 6,
where the positive and negative values (Dds±a) showed
down-®eld and up-®eld shifts respectively for nuclei of
syn rotamer (1a), while in case of 13C nuclei of anti rotamer
(1b) positive and negative values (Dds±a) described up-®eld
and down-®eld shifts, respectively. These data supported the
structures of 1a and 1b as the Z (syn) rotamer and the E
(anti) rotamer, respectively.
The CD spectrum of jafrine, showed a positive Cotton effect
in the range 217±300 nm, implying R con®guration (bH,
aCH3) at C-3.7 Thus, in the light of the above experimental
detail the structure of jafrine was determined to be (1)-3a-
methyl-4-N-acetyl-10-caproyl-11-methoxy-3,4,5,6-tetra-
hydro-b-carboline (1, Fig. 1), which was substantiated by
the diagnostic fragment ions (Fig. 2 and Section 3) in the
mass spectrum particularly at m/z 341 (M12CH3); while
m/z 300 arose due to the McLafferty rearrangement of
C-10 acyl group and m/z 285 formed as a result of RDA
fragmentation. Tetrahydroharmine may be envisaged as a
possible intermediate in the biosynthesis of jafrine.
1
The H NMR chemical shift data of 1 in different solvents
have also been obtained, to study the in¯uence of their
polarity on Z/E isomers ratios. Thus, the H NMR spectra
1
(Table 1) of 1 recorded in C6D6, CDCl3, C3D6O, and
CD3OD, showed the coexistence of both Z and E isomers
in the ratio of 31.0:1.0; 6.0:1.0; 3.0:1.0; and 3.2:1.0, respec-
tively. From the above-mentioned results, it may be inferred
that the amount of the Z rotamer (with respect to the E
rotamer) would decrease on increasing solvent polarity.
The presence of intramolecular hydrogen bonding between
1-N-H and 4-N-carbonyl, is responsible for the greater
amount of the Z isomer (1a) over the E isomer (1b),
1
An interesting feature of the H NMR spectrum (CDCl3,
Table 1) of 1 is that the compound exists in two forms, 1a
and its isomer 1b, in 6:1 ratio (Fig. 1), which was inferred by
the presence of double signals and their integrals. This is
due to the restricted rotation along the C±N bond of the

S. Faizi, A. Naz / Tetrahedron 58 (2002) 6185±6197
6191
Figure 1. Jafrine (1) and its Z (syn) and E (anti) rotamers.
Figure 2. Mass fragmentation pattern in 1.

6192
S. Faizi, A. Naz / Tetrahedron 58 (2002) 6185±6197
Table 6. 13C NMR chemical shift differences (Dds±a) of syn (Z) and anti (E)
rotamers of compounds 1 and 3 in CDCl3 and CDCl31CD3OD, respectively
NMR spectrum of 3 (Table 3) in CDCl3, exhibited exactly
the same chemical shift values and multiplicities for ring C
protons as observed in case of 1. Here also the E rotamer,
which is more stable than the Z rotamer with respect to steric
interactions, exists in high ratio in more polar protic solvents
as well as in polar aprotic solvents (Tables 3 and 4). The 13C
NMR spectrum of 3 (Table 5) also showed the presence of Z
(syn) and E (anti) rotamers, and the positive and negative
values (Dds±a) were similar to those observed for 1 (Table
6).
Carbons
Dds±aˆd 13C syn2d 13C anti
(1)
(3)
2b
3a
5a0
6b0
7g
8
11.5270
24.2204
15.3121
10.8922
22.5065
±
±
±
±
±
±
11.0570
24.2228
15.1250
10.8787
21.5120
21.5240
20.2800
21.4950
20.1420
10.5191
20.1320
21.1680
21.1660
10.3290
10.2273
9
The impact of the steric factor is nicely shown by compound
6, which is the 1-N,4-N-diacetylated derivative, obtained
through Friedel Crafts acetylation of 3. The HR EIMS of
10
11
12
13
14
15
16
17±
6
showed molecular ion peak at m/z 300.1454
21.2446
22.3090
10.3758
(C17H20N2O3). The IR spectrum exhibited a strong peak at
1691 cm21 for the carbonyl group (1-N-acetyl and 4-N-
acetyl) and no absorbance for N±H. The 1H NMR spectrum
(CDCl3, Table 2), also contained no resonance for indolic
N±H. Instead it revealed that indolic N±H has been replaced
by an acetyl group, as it has a down-®eld value for an
although the possible existence of steric hindrance between
the 4-N-carbonyl and the methyl group at C-3 (as shown by
its Drieding model) would destabilize it. When the solvent
polarity (from benzene to methanol) increases, the possi-
bility of intermolecular hydrogen bonding between solute
and solvent molecules also increases, with the increase in
the amount of the E rotamer (1b) and decrease of the Z
rotamer (1a), here the absence of intramolecular hydrogen
bonding in 1, steric interaction plays its part.
1
N-acetyl signal at d 2.74. Other H NMR spectral features
are same as those of 3, except for H-12 (7.35, d, Jˆ2.5 Hz)
and H-3 (6.35, br.q, Jˆ7.0 Hz), which appeared further
down-®eld due to the presence of 1-N-acetyl group. Thus
the structure of 6 was elucidated as 3-methyl-1-N,4-N-
diacetyl-11-methoxy-3,4,5,6-tetrahydro-b-carboline, which
exists in Z and E forms in a ratio of 1.0:1.4, respectively. In
this case the steric contribution allowed the E rotamer to be
the major one. Here the indolic nitrogen has an acetyl group,
so the intramolecular hydrogen bonding with 4-N-carbonyl
was not possible, and the steric factor controls the ratio of
Z/E forms.
This phenomenon of Z/E isomerism was also observed in
other 4-N-acetyl b-carboline derivatives, which were
studied for the con®rmation of structural features of jafrine
(1). Thus, 4-N-acetyl tetrahydroharmine (3), which was
obtained from the acetylation of available tetrahydro-
Finally the structure of 1 was con®rmed by the synthesis of
its racemate, (^) jafrine, which was carried out in two steps
1
harmine (2) showed coexistence of Z/E rotamers. The H
Table 7. NMR data (ppm) of 4, 5 and 9 in CDCl3 at 500 MHz
Position
4 dH
8.81 br.sa
5 dH
8.82 br.sa
9 dH
9 dC
1
9.04 br.sa
±
2
3
3a
4
5
±
±
±
±
±
±
136.73b
123.92b
126.50b
124.21
125.11b
154.69
92.80
138.52b
22.46
40.57
±
202.46
43.63
24.79
31.82
22.57
13.97
196.72
24.55
55.70
171.92
22.59
±
7.54 d (9.0)
6.82 dd (2.0, 9.0)
±
6.74 d (2.0)
±
7.54 d (9.0)
6.81 dd (2.5, 9.0)
±
6.75 d (2.0)
±
8.01 s
±
6
±
7
7a
6.77 s
±
3.28 t (6.5)
3.51 q (6.5)c
5.89 br.t (6.7)a
±
2.99 t (7.5)
1.68 m
1.32 m
1.26 m
0.86 t (6.5)
±
2.66 s
3.91 s
±
±
±
3.28 t (7.0)
10
3.28 t (6.5)
3.55 q (6.5)c
5.91 br.t (6.5)a
±
2.90 t (7.0)
1.61 m
1.32 m
1.24 m
0.86 t (7.0)
±
200
3.54 q (6.5)c
300
5.83 br.t (6.5)a
100
±
±
±
±
±
±
±
200
3
400
500
600
2-CO
2-COCH3
6-OCH3
30-CO
30-COCH3
±
3.84 s
±
1.89 s
2.61 s
3.84 s
±
1.90 s
1.93 s
a
Disappeared on shaking with D2O.
Assignments may be reversed.
On D2O shake converted into triplet (Jˆ6.5 Hz).
b
c

S. Faizi, A. Naz / Tetrahedron 58 (2002) 6185±6197
6193
Scheme 1. Possible mechanism for the formation of 4 from 3.
starting from an authentic sample of (^)-3,4,5,6-tetrahydro-
harmine (2). In the ®rst step, 2 was treated with acetic
anhydride to give (^)-4-N-acetyl tetrahydroharmine (3)
regioselectively. In the second and last step, 3 was subjected
to Friedel Crafts acylation with hexanoyl chloride in the
presence of a catalytic amount of a Lewis acid. The Rf
of C-3 epimerization of reserpine in acidic media as well as
acid prompted substitution reaction at C-2 of tetrahydro
b-carboline.12 The formation of compound 5 may be
rationalized by the auto-oxidation13 of 3 during the Friedel
Crafts reaction (Scheme 2).
1
value and also the spectral data (UV, IR, H NMR, EIMS)
Furthermore, from the key intermediate 3, employing
Friedel Crafts conditions, the synthesis of a new b-carboline
alkaloid 7 has also been accomplished, which, possesses an
acetyl group at C-10 in place of the caproyl moiety of 1.
Here, 1-N,4-N-diacetylated b-carboline (6) as described
above, 4-N,12-diacetylated b-carboline (8) and ring C
cleaved, auto-oxidized product (5) were also obtained.
The HR EIMS of compound 7 gave the molecular formula
C17H20N2O3 (300.1461). Its UV and IR spectra were similar
of synthetic (^)-1 and natural (1)-1 were found to be
identical. A very low yield of synthetic (^)-1 was obtained
due to the competition of the formation of two degraded
compounds (4 and 5) (2-acetyl tryptamine derivatives),
having interesting chemistry to explain, along with other
minor products.
The HR EIMS of 4 gave the molecular formula C19H26N2O3
(330.1934), while its IR spectrum showed N±H absorption
at 3351 cm21 along with the carbonyl peak at 1683 for 2-
1
to those of 1. The H NMR spectrum (CDCl3, Table 2)
revealed that it has an acetyl group (d 2.72, 3H, s) at C-10
of indole instead of a caproyl moiety in case of 1, rest of the
resonance patterns were same as those of 1. Consequently
the structure of 7 was elucidated as 3-methyl-4-N,10-di-
acetyl-11-methoxy-3,4,5,6-tetrahydro-b-carboline, which
exists in Z and E forms (7a, 7b) in a ratio of 5.4:1.0, respec-
1
and 30-carbonyl groups. The H NMR spectrum (CDCl3,
Table 7) of 4 showed the same resonance patterns for ring
A protons, as that of 3, however, H-4, H-5 and 1-N-H
appeared further down-®eld due to the presence of the
caproyl group in the indolic chromophore at C-2. The shifts
at d 3.28, 3.55, 5.91 and 1.89 showed ring C cleaved moiety
at C-3. Thus the structure of 4 was elucidated as 3-(2-
acetamidoethyl)-2-caproyl-6-methoxyindole.
1
tively, as revealed by the H NMR integral. The molecular
formula of compound 8 was identical to that of 7
(C17H20N2O3, HR EIMS, 300.1465). Its spectral data (UV,
IR, Mass, 1H NMR) re¯ected that it was a regioisomer of 7
and elucidated its structure as 3-methyl-4-N,12-diacetyl-11-
methoxy-3,4,5,6-tetrahydro-b-carboline. The 1H NMR
spectrum of 8 showed Z/E rotational isomerism in a ratio
of 3.3:1.0, respectively (Table 2). Of the compounds (4±8)
The spectral data of 5 determined its structure as 3-(2-
acetamidoethyl)-2-acetyl-6-methoxyindole.11 The possible
mechanism for the formation of compound 4 is depicted
in Scheme 1 which is supported by the reported mechanism

6194
S. Faizi, A. Naz / Tetrahedron 58 (2002) 6185±6197
Scheme 2. Plausible mechanism for auto-oxidation of 1 to 9 and 3 to 5.
discussed above, only compound 5 is known in the literature
as a synthetic product11 while 4, 6±8 are new chemical
entities.
for all 21 carbons. Its 1H NMR spectrum (Table 7) showed
the structural similarity with 1, except for ring C protons, at
d 3.28 (t, Jˆ7.0 Hz, 2H), 3.51 (q, Jˆ7.0 Hz, 2H), 5.89 (br.t,
Jˆ6.7Hz, 1H), 1.93 (s, 3H) and 2.66 (s, 3H) ascribed to
H-10, H-20, H-30, 30-COCH3 and 2-COCH3, respectively.
These data indicated the presence of an acetyl group at
C-2 and a cleaved ring C in 9. Furthermore, the chemical
shift values of the other protons (H-9, H-12, 11-OCH3)
especially the indolic N±H which shifted down-®eld (d
9.04, br.s) as compared to 1, reaf®rmed the presence of an
electron withdrawing group at C-2. The 13C NMR spectra
also resembled that of 1, except for changes due to the
opening of ring C and additional substitution of an acetyl
group at C-2 of indole. Thus its structure was elucidated as
3-(2-acetamidoethyl)-2-acetyl-5-caproyl-6-methoxy indole,
which is hitherto unreported in the literature. It is interesting
to note that this transformed product (9) is structurally simi-
lar to the synthetic compounds 4, and 5, which were
produced in the Friedel Crafts acylation of 3. Furthermore,
compound 5 was also formed from 3 by auto-oxidation
without providing Friedel Crafts reaction condition.
In the series of indole alkaloids, derivatives of simple
b-carbolines are naturally less abundant, especially
alkaloids having substitution of an acyl group at 1-N or
4-N.3,4 Jafrine (1) is the ®rst b-carboline alkaloid to have
been found thus far in the genus Tagetes, though the
presence of indole in the leaf oil of T. erecta has been
reported in literature.14 Furthermore, it is also the ®rst
instance of isolation of a b-carboline from nature bearing
a long chain carbonyl function in the A ring. The isolation of
a b-carboline having a carbon substituent in the A ring has
only once been reported, however, there are many reports of
isolation of b-carbolines possessing a carbon substituents at
ring C.3,4 It is important to note that there are examples of
naturally occurring carbazole alkaloids having carbon
substituents both at ring A and C.4
During the 1H NMR studies on the Z/E rotational isomerism
of compound 1, it was observed that 1 has transformed into
another compound jafrinine (9), which is more polar than 1
as indicated by TLC. The EIMS spectrum of 9 showed the
M1 peak at m/z 372 (HR EIMS, 372.2033, C21H28N2O4).
The 13C NMR spectrum (Table 7) is in agreement with the
molecular formula deduced from the HR EIMS accounting
The transformation of compound 1 into 9, and 3 into 5, at
room temperature, suggested that these compounds are
inherently unstable at the C-3 position, which is due to the
presence of an amide group at 4-N. In the 1H NMR spectra
of 1 and 3, the down-®eld signal of H-3 at d 5.73 and 5.71,

S. Faizi, A. Naz / Tetrahedron 58 (2002) 6185±6197
6195
respectively, also showed its instability and propensity for
radical formation. As reported in the literature13 the weakly
bonded protons (C±H) for example those adjacent to double
bond and carbonyl group can form radicals, thus auto-oxida-
tion with triplet molecular oxygen takes place. It may be
suggested that the auto-oxidation of 1 and 3 (Scheme 2),
progress through the radical formation at C-3 which reacted
with molecular oxygen of air to form their respective C-3
peroxide derivatives. The peroxides collapsed to C-3
hydroxy compounds and then converted into ring C cleaved
These observations are in agreement with the fact that
alkaloids are unstable compounds towards their extraction,
isolation and analysis procedures, where conditions such as
pH, heat, light and organic solvents, all play important role
in artifact formation.15,16
3. Experimental
3.1. General
1
products 9 and 5 respectively. From the step by step H
Optical rotation was measured with Schmidt & Haansch
Polartronic-D while CD spectrum was recorded on
JASCO spectrophotopolarimeter J-600. UV (in MeOH)
and IR (in CHCl3) spectrum was run on Hitachi-U-3200
and JASCO-A-302 spectrophotometers, respectively. The
EI, FAB positive, FAB negative and HREI mass spectra
were recorded on Finnigan MAT-112, and JMS HX-110
spectrometers. The 1H NMR spectra were recorded in
C6D6, CDCl3, C3D6O, CD3OD, C5D5N and C2D6SO at
room temperature (308C) using Bruker Aspect AM-500
spectrometer operating at 500 MHz, with spectra referenced
to residual protiodeuterio solvent signals. While 13C NMR
spectra (Broad Band and DEPT) were run on a Bruker
Aspect AM-300 and AM-400 operating at 75 and
100 MHz, respectively. The chemical shifts are in ppm
(d) and coupling constants (J) are in Hz. The 13C NMR
spectral assignments have been made partly through
DEPT and HMQC spectra and partly through comparison
with the reported values of similar compounds.5,6,17 The
purity of compounds was checked on silica gel GF254 coated
plates.
NMR analysis of 1 and 3 it has been observed that the
auto-oxidation process of 1 was faster than 3. This might
be due to the presence of caproyl group at C-10 of indolic
moiety in 1, which also increases the instability of H-3
(decrease in the bond energy of 3-C±H) and its ease towards
auto-oxidation. This process of auto-oxidation of 4-N-acetyl
tetrahydro b-carbolines can be developed into a synthetic
methodology for obtaining tryptamine derivatives, which
possess important biological activities.3,4
It is interesting to note that during these studies, the decom-
position of teterahydroharmine (2) was also observed in
1
chloroform solution of the H NMR sample, which gave
after ®fteen days exclusively 3,4,5,6-tetradehydro deriva-
tive (harmine, 10, see Section 3)5c probably through a
radical mechanism. The same type of conversion has been
witnessed previously in case of reserpine when its chloro-
form solution transformed into the 3,4,5,6-tetradehydro
reserpine.15
3.2. Plant material
The red ¯owers of T. patula were collected in the month of
April 1998 from Karachi University campus. A voucher
sample (KUH GH No. 67280) is preserved in the Botany
department, Karachi University, Karachi, Pakistan.
3.3. Extraction and isolation
The fresh, undried, and uncrushed red ¯owers (600 g) of T.
patula were extracted with petroleum ether (2.0 L£3) at
room temperature, and solvent of combined extracts was
evaporated under reduced pressure, yielding an oily residue
(3.20 g). This was dissolved in water (15 ml) to give a
whitish suspension which was decanted affording a water
insoluble (JFP, 3.14 g) and soluble fractions, the latter was
extracted with chloroform. The chloroform phase after
drying on sodium sulfate anhydrous, and evaporation of
solvent furnished 35.40 mg residue, which was subjected
to preparative thin layer chromatography (Kiesel gel254
,
petroleum ether/ethyl acetate, 2:8) furnishing jafrine (1)
(21.4 mg) showing a single spot on tlc (Rfˆ0.46, petroleum
ether/ethyl acetate, 2:8).
3.3.1. 3a-Methyl-4-N-acetyl-10-caproyl-11-methoxy-3,4,
5,6-tetrahydro-b-carboline, (jafrine) (1). Yellow gum,
26
[a]D ˆ119.23 (c 0.10, CHCl3); CD (CHCl3, 29.08C),
lmax (D1): 385 (10.6), 367( 11.5), 353 (10.8), 340
(11.6), 329 (20.2), 317( 11.8), 305 (20.1), 292 (11.4),
256 (10.5), and 217( 10.4); EIMS m/z (%) 356 (M1, 89),

6196
S. Faizi, A. Naz / Tetrahedron 58 (2002) 6185±6197
341 (100), 327(17), 313 (19), 300 (33), 299 (88), 297(25),
286 (18), 285 (85), 241 (14), 227(19), 226 (11), 214 (27),
213 (15), 184 (10), 170 (12), 156 (10), and 55 (6); HR EIMS
m/z 356.2078 (M1, calculated for C21H28N2O3, 356.2099),
341.1907(M 12CH3, C20H25N2O3), 328.1844 (a,
C19H24N2O3), 301.1511 (b, C17H21N2O3), 297.1599 (c,
C18H21N2O2), 214.0784 (d, C12H10N2O2), 98.0801 (e,
C6H10O). For 1H and 13C NMR data, see Tables 1, 5, and 6.
[M12(HNCOCH311H1),
(C12H12NO2). For H NMR data see Table 7.
C13H13NO2],
202.0856
3.5. Friedel Crafts acetylation of compound 3
A catalytic amount of aluminium chloride was added into a
solution of 3 (1 g, 3.8 mmol) in acetic anhydride (1 ml,
10 mmol) and kept at room temperature for 48 h. After
separation of aluminium chloride the resulting reaction
mixture was subjected to PTLC (silica gel GF254, petroleum
ether/ethyl acetate, 2:8) furnishing compounds 6 (15.3 mg),
8 (4.2 mg), 7 (10.3 mg), and 5 (32.4 mg) in increasing order
of polarity.
3.3.2. (^)-3-Methyl-11-methoxy-3,4,5,6-tetrahydro-b-
carboline (2). Light pink amorphous powder, UV
(MeOH) lmax: 294, 278, 217, and 199 nm; IR (CHCl3)
n
max: 3491, 2952, 2855, 1630, 1451, 1282 and 1163 cm21
;
EIMS m/z (%) 216 (M1, 54), 201 (100), 187(15), 186 (13),
172 (15), and 100 (6); HR EIMS m/z 216.1259 (M1, calcu-
lated for C13H16N2O, 216.1262). For H NMR data, see
3.5.1. (^)-3-Methyl-1-N,4-N-diacetyl-11-methoxy-3,4,
5,6-tetrahydro-b-carboline (6). White amorphous powder,
UV (MeOH) lmax: 293, 282, 222, 210, and 202 nm; IR
(CHCl3) nmax: 2953, 2854, 1691, 1620, 1425, 1302, and
1151 cm21; HR EIMS m/z (%) 300.1454 (M1, calculated
for C17H20N2O3, 300.1473, 94), 285.1258 (M1215,
1
Table 2.
3.3.3. Acetylation of (^)-tetrahydroharmine (2). Tetra-
hydroharmine (2) (2 g, 9.2 mmol) was dissolved in 2.0 ml
(2.1 mmol) acetic anhydride at room temperature to readily
C16H17N2O3,
97)
243.1125
[M12(COCH3±CH2),
1
give compound (^)-4-N-acetyl-tetrahydroharmine
3
C14H15N2O2, 100], and 201.1029 (C12H13N2O, 69). For H
NMR data see Table 2.
(2.34 g) as colorless needles; (methanol/benzene; 1:1); mp
198±2008C; UV (MeOH) lmax: 276, 266, 242, 229, 203 nm;
IR (CHCl3) nmax: 3305, 3051, 2953, 2852, 1661, 1621, 1430,
and 1162 cm21; EIMS m/z (%) 258 (M1, 84), 244 (16), 243
(96), 215 (12), 201 (100), 199 (11), 186 (45), 172 (13), and
129 (12); HR EIMS m/z 258.1369 (M1, calculated for
C15H18N2O2, 258.1368), 243.1135 (M1215, C14H15N2O2).
For 1H and 13C NMR data see Tables 3±6.
3.5.2. (^)-3-Methyl-4-N,10-diacetyl-11-methoxy-3,4,5,6-
tetrahydro-b-carboline (7). Yellowish brown amorphous
powder, UV (MeOH) lmax: 299, 285, 251, 212, and 203 nm;
IR (CHCl3) nmax: 3305, 3042, 2952, 2849, 1680, 1663, 1619,
1451, and 1162 cm21; EIMS m/z (%) 300 (M1, 91) 285
(100), 243 (87), 203 (15), 201 (32), 160 (14), and 97 (13);
HR EIMS m/z (%) 300.1461 (M1, calculated for
1
C17H20N2O3, 300.1473). For H NMR data see Table 2.
3.4. Synthesis of (^)-1 from (^)-3 through Friedel Crafts
acylation (hexanoylation)
3.5.3. (^)-3-Methyl-4-N,12-diacetyl-11-methoxy-3,4,5,6-
tetrahydro-b-carboline (8). Yellowish brown amorphous
powder, UV (MeOH) lmax: 298, 285, 252, 212, and 203 nm;
IR (CHCl3) nmax: 3310, 3039, 2951, 2852, 1682, 1664, 1621,
1449, and 1162 cm21; EIMS m/z (%) 300 (M1, 95), 285
(100), 243 (89) and 201 (42); HR EIMS m/z (%) 300.1465
Hexanoyl chloride (6 ml, 43 mmol) and catalytic amount of
aluminium chloride were added to a solution of (^)-4-N-
acetyl tetrahydroharmine (3) (82 mg, 0.3 mmol) in nitroben-
zene (5 ml) and the reaction mixture was kept at room
temperature for 48 h and then ®ltered to separate aluminium
chloride. The ®ltrate was subjected to preparative thin layer
chromatography (PTLC, silica gel GF254, petroleum ether/
ethyl acetate, 2:8) affording (^)-1 (9.52 mg) along with 4
(26.2 mg), 5 (11.4 mg) and other minor products. All spec-
tral data of (^) jafrine (1) including UV, IR, EIMS and 1H
NMR, are same as those of (1) jafrine (1).
(M1, calculated for C17H20N2O3, 300.1473). For H NMR
data see Table 2.
1
3.5.4. 3-(2-Acetamidoethyl)-2-acetyl-5-caproyl-6-meth-
oxyindole (9). Light brown gum, UV (MeOH) lmax: 332,
282, 261, 253, and 221 nm; IR (CHCl3) nmax: 3361, 3104,
2951, 2857, 1679, 1621, 1451, and 1189 cm21; EIMS m/z
(%): 372 (M1, 37), 357 (29), 341 (79), 339 (17), 330 (59),
316 (13), 297(35), 285 (68), 274 (44), 242 (55), 239 (100),
231 (15), 216 (34), and 204 (32); HR EIMS m/z 372.2033
3.4.1. 3-(2-Acetamidoethyl)-2-caproyl-6-methoxyindole
(4). Light brown gum, UV (MeOH) lmax: 332, 283, 261,
254, 226, 216 and 203 nm; IR (CHCl3) nmax: 3351, 3105,
2952, 2851, 1683, 1621, 1452, and 1185 cm21; EIMS m/z
(%): 330 (M1, 32) 271 (100), 258 (25), 243 (24), 231 (16),
215 (50), 188 (42), and 169 (31); HR EIMS m/z 330.1934
(M1, calculated for C21H28N2O4, 372.2049). For 1H and 13
NMR data see Table 7.
C
3.5.5. Harmine (10). Light yellow powder, UV (MeOH)
max: 345, 327, 301, 272, 240, 219 nm; IR (CHCl3) nmax
1
(M1, calculated for C19H26N2O3, 330.1943). For H NMR
l
:
data see Table 7.
3071, 2923, 1623, 1568, 1447, 1280, 1160, 1023 and
814 cm21; EIMS m/z (%): 212 (M1, 100), 197(20), 189
(75), 176 (73), 174 (42), 169 (31), 162 (50) and 150 (35);
HR EIMS m/z 212.0974 (M1, calculated for C13H12N2O,
3.4.2.
(5). Light brown amorphous powder, UV (MeOH) lmax
3-(2-Acetamidoethyl)-2-acetyl-6-methoxyindole
:
1
331, 280, 262, 255, and 218 nm; IR (CHCl3) nmax: 3353,
3101, 2902, 1681, 1625, 1447, 1191, and 1116 cm21; EIMS
m/z (%): 274 (M1, 52), 215 (100), 202 (45), 188 (20), 160
(13), 149 (19), and 71 (27); HR EIMS m/z 274.1301
(M1, calculated for C15H18N2O3, 274.1317), 215.0943
212.0949); H NMR (CDCl3, 500 MHz): d 8.17(1H, br. s,
H-1), 8.28 (1H, d, Jˆ5.5 Hz, H-5), 7.69 (1H, d, Jˆ5.5 Hz,
H-6), 7.94 (1H, d, Jˆ8.5 Hz, H-9), 6.88 (1H, dd, Jˆ2.0,
8.5 Hz, H-10), 6.95 (1H, d, Jˆ2.0 Hz, H-12), 2.77 (3H, s,
H-3-Me) and 3.93 (3H, s, H-11-OMe).

S. Faizi, A. Naz / Tetrahedron 58 (2002) 6185±6197
6. Abreu, P.; Pereira, A. Nat. Prod. Lett. 2001, 15, 43±48.
6197
References
7. (a) Tsuda, M.; Watanabe, D.; Kobayashi, J. Heterocycles
1999, 50, 485±488. (b) Stockigt, J.; Zenk, M. H. J. Chem.
Soc., Chem. Commun. 1977, 646±648.
1. (a) Manjunath, B. L. Raw Material; The Wealth of India, Vol.
10; CSIR: New Delhi, 1969 pp 109±112. (b) Fakim, A. G.;
Gueho, J.; Bissoondoyal, M. S. Int. J. Pharmacog. 1997, 35,
237±254. (c) Grigorescu, E.; Segal, B.; Pavelescu, M.;
Stanciu, V.; Dorneanu, V.; Stanescu, U.; Ionescu, A. Rom.
Ro 90, 722 (C1. A61 K31/70), 10 Dec 1986, Appl. 114,
983, 23 Aug 1984, 3 pp.; Chem. Abstr. 1987, 107, 223318p.
(d) Wells, C.; Bertsch, W.; Perich, M. Chromatographia 1993,
35, 109±115. (e) Vasudevan, P.; Kashyap, S.; Sharma, S.
Biores. Technol. 1997, 62, 29±35.
8. (a) Cox, C.; Lectka, T. Acc. Chem. Res. 2000, 33, 849±858.
(b) Fischer, G. Chem. Soc. Rev. 2000, 29, 119±127.
9. Wilson, N. K.; Stothers, J. B. In Stereochemical Aspects of 13
C
NMR Spectroscopy, Eliel, E. L., Ed.; Topics in Stereo-
chemistry; Wiley: New York, 1974; Vol. 8, pp 1±158.
Â
Â
Â
Â
Â
10. Lukats, A. P.; Kocsis, A.; Szabo, L. F.; Podanyi, B. J. Nat.
Prod. 1999, 62, 1492±1499.
11. Rahman, A. J. Chem. Soc., Perkin Trans. 1 1972, 736±738.
12. (a) Siddiqui, S.; Begum, S.; Siddiqui, B. S. Pakistan J. Sci.
Ind. Res. 1983, 26, 53±58. (b) Gaskell, A. J.; Joule, J. A.
Tetrahedron 1967, 23, 4053±4063.
2. (a) Kagan, J. Progress in the Chemistry of Organic Natural
Products; Zechmeister, L., Ed.; 1991; Vol. 56, pp 87±169.
(b) Ivancheva, S.; Zdravkova, M. Fitoterapia 1993, 64, 555
and references cited therein. (c) Menelaou, M. A.; Fronczek,
F. R.; Hjortso, M. A.; Morrison, A. F.; Foroozesh, M.;
Thibodeaux, T. M.; Flores, H. E.; Fischer, N. H. Spectrosc.
Lett. 1991, 24, 1405±1413. (d) Karrer, P.; Jucker, E.; Steinlin,
K. Helv. Chim. Acta 1947, 30, 531±535.
13. (a) Solomons, T. W. G. Radical Reactions, and Conjugated
Unsaturated Systems; Organic Chemistry, Wiley: New York,
1996 pp 366±414 and 496±533. (b) Gilbert, A.; Baggott, J.
Photo-Oxygenation Reactions; Essentials of Molecular
Photochemistry, Oxford Blackwell Scienti®c: London, 1991
pp 501±525.
3. Allen, J. R. F.; Holmstedt, B. R. Phytochemistry 1980, 19,
1573±1582.
14. Machado, M. I. L.; Silva, M. G. V.; Matos, F. J. A.; Craveiro,
A. A.; Alencar, J. W. J. Essent. Oil Res. 1994, 6, 203±205.
15. Svendsen, A. B.; Verpoorte, R. Chromatography of Alkaloids;
Elsevier: Amsterdam, 1983 pp 51±58.
4. Husson, H. P. In Simple Indole Alkaloids including
b-Carbolines and Carbazoles, Brossi, A., Ed.; The Alkaloids;
Academic/Harcourt Brace Javanovich: Orlando, 1985; Vol.
26, pp 1±51.
16. Lounasmaa, M.; Hanhinen, P. J. Nat. Prod. 2000, 63, 1456±
1460.
5. (a) Siddiqui, S.; Khan, O. Y.; Faizi, S.; Siddiqui, B. S. Hetero-
cycles 1988, 27, 1401±1410. (b) Ayer, W. A.; Browne, L. M.
Can. J. Chem. 1970, 48, 1980±1984. (c) Siddiqui, S.; Khan,
O. Y.; Faizi, S.; Siddiqui, B. S. Heterocycles 1989, 29, 521±
527.
Â
17. Morales-Rõso, M. S.; EspinÄeira, J.; Joseph-Nathan, P. Magn.
Reson. Chem. 1987, 25, 377±395.