Synthesis of (±)-Glaucine and (±)-Neospirodienone via an One-Pot Bischler-Napieralski Reaction and Oxidative Coupling by a Hypervalent Iodine Reagent

Article abstract of DOI:10.1002/hlca.200490005

Condensation of 3,4-dimethoxybenzeneethanamine (3d) and various benzeneacetic acids, i.e., 4a-e, via a practical and efficient one-pot Bischler-Napieralski reaction, followed by NaBH₄ reduction, produced a series of 1-benzyl-1,2,3,4-tetrahydroisoquinolines, i.e., 5a-e, in satisfactory yields (Scheme 3). Oxidative coupling of the N-acyl and N-methyl derivatives 6a-e of the latter with hypervalent iodine ([IPh(CF ₃COO)₂]) yielded products with two different skeletons (Scheme 4). The major products from N-acyl derivatives 6a-c were (±)-N-acylneospirodienones 2a-c, while the minor was the 3,4-dihydroisoquinoline 7. (±)-Glaucine (1), however, was the major product starting from N-methyl derivative 6e. Possible reaction mechanisms for the formation of these two types of skeleton are proposed (Scheme 5).

Full text of DOI:10.1002/hlca.200490005

Helvetica Chimica Acta Vol. 87 (2004)
167
Synthesis of (Æ)-Glaucine and (Æ)-Neospirodienone via an One-Pot
BischlerÀNapieralski Reaction and Oxidative Coupling by a Hypervalent
Iodine Reagent
by Wei-Jan Huang, Om V. Singh, Chung-Hsiung Chen, and Shoei-Sheng Lee*
School of Pharmacy, College of Medicine, National Taiwan University, 1 Jen-Ai Road, Sec. 1, Taipei,
Taiwan 100, Republic of China
(fax: (886) 2-2391-6127; e-mail: shoeilee@ha.mc.ntu.edu.tw)
Condensation of 3,4-dimethoxybenzeneethanamine (3d) and various benzeneacetic acids, i.e., 4a e, via a
practical and efficient one-pot Bischler Napieralski reaction, followed by NaBH4 reduction, produced a series
of 1-benzyl-1,2,3,4-tetrahydroisoquinolines, i.e., 5a e, in satisfactory yields (Scheme 3). Oxidative coupling of
the N-acyl and N-methyl derivatives 6a e of the latter with hypervalent iodine ([IPh(CF3COO)2]) yielded
products with two different skeletons (Scheme 4). The major products from N-acyl derivatives 6a c were (Æ)-
N-acylneospirodienones 2a c, while the minor was the 3,4-dihydroisoquinoline 7. (Æ)-Glaucine (1), however,
was the major product starting from N-methyl derivative 6e. Possible reaction mechanisms for the formation of
these two types of skeleton are proposed (Scheme 5).
Introduction. Glaucine (1), a naturally occurring aporphine alkaloid, was recently
demonstrated to be a potent anti-inflammatory agent [1]. It had been prepared by
oxidative coupling of 1-(3,4-dimethoxybenzyl)-1,2,3,4-tetrahydro-6,7-dimethoxy-2-
methylisoquinoline with some oxidative reagents such as VIII, CrIII, and PbIV [2 4].
These reagents, however, are usually difficult to handle and have all toxic properties,
which limit their application for large-scale synthesis. During the past decade,
arylbis(alkanoato-kO)-iodines (ˆ [bis(acyloxy)iodo]arenes) have been widely used
as oxidation agent. Among them, [IPh(CF3COO)2] (PFAI) possesses an oxidation
property equivalent to that of ThIII, HgII, and PbIV [5] but is devoid of toxic properties.
More recently, PFAI has been used for the generation of aryl radical cations via a
single-electron-transfer (SET) pathway (Scheme 1) [6]. The intermediate could be
trapped by the internal or external nucleophiles such as azide [6a], thiocyanide [7], and
others [8], which afforded the substituted benzene rings. We thought that intra-
molecular coupling of two sets of aryl radical cations would give rise to a new biarene
connection. We now describe our efforts to reach this goal, which led to the synthesis of
(Æ)-glaucine (1) and (Æ)-neospirodienones 2 starting from a 1-benzyl-1,2,3,4-tetrahy-
droisoquinoline (Scheme 2).
Result and Discussion. During the preparation of the amide by condensation of
benzeneethanamine (3d) and benzeneacetyl chloride, prepared in situ by reacting the
carboxylic acid 4a with phosporyl chloride (POCl3), two products were obtained. The
less polar one was the expected corresponding amide. The polar one showed a positive
response to Dragendorff×s reagent, suggesting the presence of an amine formed by
subsequent BischlerÀNapieralski reaction of the amide with the excess of the reagent

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Helvetica Chimica Acta Vol. 87 (2004)
Scheme 1. Intramolecular Oxidative Coupling with PFAI
Scheme 2
POCl3. Optimization of the reaction conditions revealed that, with 4 equiv. of POCl3,
this amine product was formed exclusively. Previous studies [9] had indicated the air
sensitivity of the amines produced in this reaction, i.e., of the 1-benzyl-3,4-
dihydroisoquinolines. Thus without further purification, the amines were reduced by
NaBH4 to give the stable 1-benzyl-1,2,3,4-tetrahydroisoquinolines. Application of this
facile approach resulted in the synthesis of the benzyltetrahydroisoquinolines 5a e
from amine 3d and corresponding benzeneacetic acids 4a e in satisfactory yields
(Scheme 3, Table 1). The poor solubility of 4-nitrobenzeneacetic acid (4e) in POCl3
impeded the formation of the corresponding amide, and thus a longer reaction time
(24 h) for a better yield of 5e was required. under similar conditions, reaction of the
benzeneethanamines 3f,g with 4d also afforded the corresponding products 5f,g in
satisfactory yields (Scheme 3, Table 1).
Reaction of the benzyltetrahydroisoquinoline 5d with trifluoroacetic anhydride
((CF3CO)2O) in pyridine yielded the N-trifluoroacetyl derivative 6a. Treatment of 6a
with PFAI (1.2 equiv.) in the presence of BF3 ¥ Et2O (2.6 equiv.) in CH2Cl2 at À408 gave

Helvetica Chimica Acta Vol. 87 (2004)
169
Scheme 3
i) POCl3, PhMe, r.t. to 1208, 3.5 h. ii) NaBH4, MeOH, r.t., 2.5 h.
Table 1. 1-Benzyl-1,2,3,4-tetrahydroisoquinolines 5 Prepared via a One-Pot BischlerÀNapieralski Reaction
5a 5b 5c
5d
5e
5f
5g
Yielda) [%]
75 73 75
70
65
78
71
M.p. (Lit. m.p.) [8]
88 90
78 80
130 132
84 86
92 94
([10]: 89 91) ([11]: 76 77) ([12]: 134 136) ([13]: 82 84) ([14]: 91 92)
a) Yield of isolated product.
dihydroisoquinoline 7 [15] (46%) and an unexpected racemic compound 2a (42%)
(Scheme 4). Compound 2a was identified as (Æ)-N-(trifluoroacetyl)neospirodienone,
which had been prepared previously by treating morphinandienone with VOF3 ¥
CF3COOH via a rearrangement mechanism [16], by comparison of its spectral data
to those reported.
The molecular formula C21H21F3NO5 of 2a was deduced from the HR-FAB-MS, exhibiting a quasi-
‡
molecular ion [M ‡ H] at m/z 424.1367. The 1H-NMRspectrum showed two sets of signals due to the existence
of s-trans and s-cis forms of the amide function, which could not be hydrolyzed under acidic or basic conditions.
The assigned structure and relative configuration at C(4a) and C(7a) were also confirmed by NOESY
1
experiments (Fig. 1), which also facilitated the H-NMRassignment as shown in Table 2.

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Helvetica Chimica Acta Vol. 87 (2004)
Scheme 4
i) Phenylbis(trifluoroacetato-kO)iodine (PFAI), CH2Cl2, À408, 3 h.
Fig. 1. NOESY of Neospirodienone 2a
To study the N-substitution effect on this oxidative coupling reaction, the
tetrahydroisoquinoline (5d) was modified with four other protecting groups, i.e.,
formyl, acetyl, methylsulfonyl, and methyl, yielding 6b e, respectively. Under the same
oxidative coupling conditions as those applied to 6a (see above), 6b e gave the
products shown in Table 3 (cf. Scheme 4). The 3,4-dihydroisoquinoline 7 could be
formed via a bond-cleavage mechanism since the starting materials 6 having a better
leaving group lead to a better yield of 7 (46% from 6a (CF3COÀN) vs. trace from 6b
(CHOÀN)). Starting from 6b (CHOÀN) or 6c (AcÀN) gave 2b and 2c, respectively, in
better yields than starting from 6a (CF3COÀN), while 6d (MeSO2ÀN) was
decomposed during the reaction, probably due to the cleavage of the protecting group
prior to the formation of the aryl radical cation.

Helvetica Chimica Acta Vol. 87 (2004)
171
Table 2. 1H-NMR Data of (Æ)-Neospirodienones 2a c. d in ppm, J in Hz.
2a
2b
2c
HÀ(C1)
6.73, 6.57 (2s)
5.80, 5.66 (2s)
4.63 (dd)a), 4.46 (t)b)
3.45, 3.19 (2dd)c)
2.98, 2.85 (2dd)d)
6.63, 6.58 (2s)
7.05, 6.96 (2s)
3.70, 3.65 (2s)
3.88 (s)
6.65, 6.48 (2s)
5.83, 5.79 (2s)
4.53, 4.23 (2dd)a)
3.26, 3.07 (2dd)c)
2.98, 2.84 (2dd)d)
6.64, 6.60 (2s)
7.01, 6.93 (2s)
3.72, 3.69 (2s)
3.88 (s)
6.68, 6.57 (2s)
5.84, 5.82 (2s)
HÀC(4)
HÀC(7a)
HaxÀC(8)
HeqÀC(8)
HÀC(9)
4.50, 4.18 (2dd)a)
3.39, 3.15 (2dd)c)
2.95, 2.83 (2dd)d)
6.62, 6.59 (2s)
7.01, 6.95 (2s)
3.68, 3.67 (2s)
3.88 (s)
HÀC(12)
MeOÀC(3)
MeOÀC(10)
MeOÀC(11)
CHOÀN(7)
3.88 (s)
3.88 (s)
8.45, 8.28 (2s)
3.88 (s)
a) J ca. 3.1, 7.5. b) J ca. 7.6. c) J ca. 7.5, 17.4.d) J ca. 3.1, 17.4.
Table 3. Oxidative Coupling Reactions of 1-Benzyl-1,2,3,4-tetrahydroisoquinolines 6a e with PFAI
Reactant
6a
6b
2b
6c
2c
6d 6e
Product(s)
2a
42
7
7
2d
1
Yielda) [%]
46 67
240 242
([16]: 243 245)
trace 70
238 240
0
33
M.p. (Lit. m.p.) [8] 244 246
([18]: 247 248)
112 114
([17]: 117 118)
a) Yield of isolated product(s).
When the N-methyl-protected tetrahydroisoquinoline 6e, a tertiary amine, was
treated with PFAI under oxidative coupling conditions, (Æ)-glaucine (1) [17] was
produced in 33% yield.
These results indicate that the inductive effect of the N-substituent influences the
positions of the stable radical cations for oxidative coupling. Hence, a plausible
mechanism is depicted in Scheme 5 to explain the two different skeletons formed under
similar condition. The bis-radical cation 8 would be first generated via a SET pathway,
for which two different resonance forms 9 can be formulated. The N-acyl-substituted
radical cation 9a c would afford the C(4a) and C(14) coupling products 10a c
(arbitrary numbering) and then, after rearrangement and isomerization, the (Æ)-N-
acylneospirodienones 2a c. The N-methyl-substituted radical cation 9e would afford
the C(8) and C(14) coupling product 10, which would isomerize to (Æ)-glaucine (1).
This study provides a practical and efficient one-pot BischlerÀNapieralski reaction
for the preparation of 1-benzyl-1,2,3,4-tetrahydroisoquinoline by using excess con-
densation reagent (4.5 equiv. of POCl3). Upon completion of this work, we found that a
similar one-pot process used for the same purpose with the same reagent had been
reported only once for the preparation of three selective benzyltetrahydroisoquinolines
[19]. We successfully applied this one-pot reaction to the preparation of a variety of
isoquinolines, such as 1-phenylisoquinolines and 1-alkylisoquinolines. By monitoring
the N-substitution of benzyltetrahydroisoquinolines, two distinct skeletons, neospiro-
dienone (see 2) and aporphine (see 1), were produced by oxidative coupling with

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Helvetica Chimica Acta Vol. 87 (2004)
Scheme 5
i) para-para Oxidative coupling. ii) ortho-para Oxidative coupling. iii) Isomerization.
[IPh(OCOCF3)2]. This novel finding and the much less toxic and easier handling
properties of [IPh(OCOCF3)2] as compared to those of heavy metal containing
reagents greatly favor the former reagent for the use in the synthesis of bioactive
alkaloids belonging to the skeletons mentioned above.
We gratefully acknowledge the National Science Council, Taiwan, R. O. C., for the support of this work
under the grant NSC89-2320-B-002-272 and the postdoctoral fellowship award to O. V. S. (NSC89-2811-B-002-
0137).

Helvetica Chimica Acta Vol. 87 (2004)
173
Experimental Part
General. TLC: silica gel, CHCl3/MeOH; visualization by UVat 254 nm and by Dragendorff×s spray reagent.
CC ˆ Column chromatography. M.p.: in open capillaries, Fisher-Johns melting-point apparatus; uncorrected.
FT-IRSpectra: Jasco DIP-181-IR-Report-100 spectrophotometer; KBr pellets; vƒ in cmÀ1 1H- and 13C-NMR:
.
Bruker DPX-200 and AMX-400; d in ppm, J in Hz. MS: JMS-SX102A (FAB-MS) and Finnigan Mat-TSQ-7000
(ESI-MS) spectrometers; in m/z (rel. %).
Tetrahydroisoquinolines 5a e: General Procedure. To a mixture of benzeneacetic acid 4a e (10.00 mmol)
and 3,4-dimethoxybenzeneethanamine (3d) (1.81 g, 10.00 mmol), POCl3 (4 ml, 43.92 mmol) was added
dropwise. After 1 h stirring at r.t., toluene (10 ml) was added and the mixture heated under reflux for 3.5 h. Then
the mixture was evaporated, the residue dissolved in MeOH (5 ml), and the soln. poured into ice. The aq. phase
was basified with 25% NH4OH soln. and extracted with CH2Cl2 (3 Â 50 ml), the combined org. phase washed
with H2O (100 ml), dried (Na2SO4), and evaporated, and the residue dissolved in MeOH (30 ml). To this soln.,
NaBH4 (946 mg, 25.00 mmol) was added portionwise during 30 min while stirring. After 2.5 h, the soln. was
evaporated, the residue suspended in CH2Cl2 (50 ml) and washed with H2O (50 ml), the org. phase dried
(Na2SO4), evaporated, and the residue purified by CC (Al2O3): 5a e (Table 1).
1,2,3,4-Tetrahydro-6,7-dimethoxy-1-(phenylmethyl)isoquinoline (5a): 1H-NMR(CDCl 3, 400 MHz): 7.33
7.32 (m, C6H5); 6.57 (s, HÀC(5)); 6.56 (s, HÀC(8)); 4.16 (dd, J ˆ 9.1, 4.7, HÀC(1)); 3.83 (s, MeOÀC(6)); 3.77 (s,
MeOÀC(7)); 3.21 3.15 (m, 2 H); 2.96 2.89 (m, 2 H); 2.75 2.69 (m, 2 H); 2.19 (br. s, NH). FAB-MS: 284 (80,
‡
[M ‡ H] ), 192 (100).
1-[(4-Bromophenyl)methyl]-1,2,3,4-tetrahydro-6,7-dimethoxyisoquinoline (5b): 1H-NMR(CDCl
,
3
400 MHz): 7.42 (d, J ˆ 8.3, HÀC(3'), HÀC(5')); 7.11 (d, J ˆ 8.3, HÀC(2'), HÀC(6')); 6.57 (s,
HÀC(5)); 6.49 (s, HÀC(8)); 4.18 (dd, J ˆ 8.6, 5.0, HÀC(1)); 3.86 (s, MeOÀC(6)); 3.76 (s, MeOÀC(7));
‡
3.18 3.12 (m, 2 H); 2.99 2.93 (m, 2 H); 2.75 2.74 (m, 2 H). FAB-MS: 362 (40, [M ‡ H] ), 192 (40), 153
(100).
1,2,3,4-Tetrahydro-6,7-dimethoxy-1-[(4-methoxyphenyl)methyl]isoquinoline (5c): 1H-NMR(CDCl
,
3
400 MHz): 7.14 (dd, J ˆ 6.6, 2.0, HÀC(2'), HÀC(6')); 6.84 (dd, J ˆ 6.6, 2.0, HÀC(3'), HÀ(5')); 6.57 (s,
HÀC(5)); 6.54 (s, HÀC(8)); 4.14 (dd, J ˆ 8.7, 5.0, HÀC(1)); 3.83 (s, MeOÀC(6)); 3.78 (s, MeO); 3.77 (s, MeO);
‡
3.22 3.10 (m, 2 H); 2.97 2.90 (m, 2 H); 2.76 2.72 (m, 2 H). FAB-MS: 314 (40, [M ‡ H] ), 192 (100).
1-[(3,4-Dimethoxyphenyl)methyl]-1,2,3,4-tetrahydro-6,7-dimethoxyisoquinoline (5d): 1H-NMR(CDCl
,
3
400 MHz): 6.80 (d, J ˆ 8.1, HÀC(5')); 6.76 (dd, J ˆ 8.1, 1.6, HÀC(6')); 6.72 (d, J ˆ 1.6, HÀC(2')); 6.61 (s,
HÀC(5)); 6.56 (s, HÀC(8)); 4.12 (dd, J ˆ 8.9, 4.4, HÀC(1)); 3.84 (s, MeO); 3.82 (s, MeO); 3.81 (s, MeO); 3.79
(s, MeO); 3.18 3.12 (m, 2 H); 2.92 2.82 (m, 2 H); 2.73 2.62 (m, 2 H); 2.19 (br. s, NH). FAB-MS: 344 (80,
‡
[M ‡ H] ), 192 (80); 153 (100).
1,2,3,4-Tetrahydro-6,7-dimethoxy-1-[(4-nitrophenyl)methyl]isoquinoline (5e): 1H-NMR(CDCl
,
3
400 MHz): 8.15 (d, J ˆ 8.8, HÀC(3'), HÀC(5')); 7.41 (d, J ˆ 8.8, HÀC(2'), HÀC(6')); 6.58 (s, HÀC(5)); 6.56
(s, HÀC(8)); 4.23 (dd, J ˆ 9.2, 4.4, HÀC(1)); 3.85 (s, MeOÀC(6)); 3.79 (s, MeOÀC(7)); 3.26 (dd, J ˆ 13.7, 4.4,
HÀC(9)); 3.19 3.14 (m, 1 H); 3.06 (dd, J ˆ 13.7, 9.2, HÀC(9)); 2.97 2.94 (m); 2.73 2.70 (m, 2 H); 2.20 (br. s,
‡
NH). FAB-MS: 329 (30, [M ‡ H] ), 192 (100).
Tetrahydroisoquinolines 5f,g. As described for 5a e, with 3,4-dimethoxybenzeneacetic acid (4d) (1.96 g,
10.00 mmol) and benzenethanamines 3f g (10.00 mmol): 5f,g (Table 1).
5-[(3,4-dimethoxyphenyl)methyl]-5,6,7,8-tetrahydro-1,3-dioxolo[4,5-g]isoquinoline (5f): 1H-NMR(CDCl 3
,
400 MHz): 6.81 (d, J ˆ 8.1, HÀC(5')), 6.76 (dd, J ˆ 8.1, 1.8, HÀC(6')), 6.73 (d, J ˆ 1.8, HÀC(2')), 6.68 (s,
HÀC(9)); 6.54 (s, HÀC(4)), 5.88 (s, OCH2O); 4.08 (dd, J ˆ 9.5, 3.8, HÀC(5)); 3.87 (s, MeO); 3.85 (s, MeO),
‡
3.15 3.10 (m, 2 H); 2.88 2.71 (m, 2 H); 2.70 2.66 (m, 2 H); 2.23 (br. s, NH). FAB-MS: 328 (70, [M ‡ H] ),
176 (100).
1-[(3,4-Dimethoxyphenyl)methyl]-1,2,3,4-tetrahydro-5,6,7-trimethoxyisoquinoline (5g): 1H-NMR(CDCl
,
3
400 MHz): 6.81 (d, J ˆ 8.1, HÀC(5')); 6.79 (dd, J ˆ 8.1, 1.6, HÀC(6')); 6.75 (d, J ˆ 1.6, HÀC(2')); 6.39 (s,
HÀC(5)); 4.24 (dd, J ˆ 9.7, 2.7, HÀC(1)); 3.98 (s, MeO), 3.84 3.83 (s, 3 MeO); 3.82 (s, MeO), 3.18 3.15 (m);
3.05 (dd, J ˆ 13.8, 2.7, 1 H, (MeO)2C6H3CH2); 2.95 2.90 (m); 2.87 (dd, J ˆ 13.8, 9.7, 1 H, (MeO)2C6H3CH2);
‡
2.80 2.76 (m), 2.60 2.54 (m), 2.72 (br. s, NH). FAB-MS: 374 (80, [M ‡ H] ), 222 (100).
Oxidative Coupling of 6a e with PFAI. General Procedure. To a soln. of 6a e (0.26 mmol) in CH2Cl2
(10 ml), a soln. of PFAI (125 mg, 0.29 mmol) and BF3 ¥ Et2O (0.18 ml, 0.68 mmol) in CH2Cl2 (10 ml) was added
dropwise at À408, and the mixture was stirred for 3 h. Then sat. aq. NaHCO3 soln. was added, the aq. phase
extracted with CH2Cl2 (25 ml  3), the extract dried (Na2SO4) and evaporated, and the residue purified by CC
(0 50% CHCl3/hexane): pure 2a c (Table 3).

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(Æ)-6,7,7a,8-Tetrahydro-3,10,11-trimethoxy-7-(trifluoroacetyl)-dibenz[d,f]indol-2(5H)-one (2a). FT-IR:
2922s, 1684s, 1656s, 1636s, 1590s, 1219s, 1145s. 1H-NMR(CDCl 3, 400 MHz): Table 2. 13C-NMR(CDCl
,
3
100 MHz); 180.7, 180.6 (2s); 156.7, 154.4 (2s); 152.1, 151.8 (2s); 151.7, 151.3 (2s); 148.7, 148.6 (2s); 127.4, 126.9
(2s); 125.2, 122.6 (2s); 123.9, 123.7 (2d); 116.3, 114.3 (2d); 111.0, 110.4 (2d); 107.9, 107.4 (2d); 60.6, 60.5 (2q);
56.1, 55.9 (2q); 55.2, 55.1 (2q); 48.1, 47.4 (2s); 45.0, 44.9 (2t); 41.2, 36.2 (2t); 33.3, 31.7 (2t). FAB-HR-MS:
‡
‡
424.1367 ([M ‡ H] , C21H21O5NF3 ; calc. 424.1372).
3,4-Dihydro-6,7-dimethoxyisoquinoline (7): 1H-NMR(CDCl 3, 400 MHz): 8.14 (s, HÀC(1)); 6.81 (s,
HÀC(8)); 6.56 (s, HÀC(5)); 6.49 (s, HÀC(8)); 3.90 (s, MeOÀC(7)); 3.88 (s, MeOÀC(6)); 3.72 3.71 (m,
2 HÀC(3)); 2.68 (t, J ˆ 8.0, 2 HÀC(4)).
(Æ)-5,6,7a,8-Tetrahydro-3,10,11-trimethoxy-2-oxodibenz[d,f]indole-7(2H)-carbaldehyde (2b). FT-IR:
2938s, 1665s, 1628s, 1588s, 1511s, 1217s, 1180s. 1H-NMR(CDCl 3, 400 MHz): Table 2. 13C-NMR(CDCl
,
3
100 MHz) 181.0, 180.9 (2s); 161.0, 160.7 (2d); 158.1, 156.2 (2s); 151.9, 151.5 (2s); 151.3, 150.9 (2s); 148.8, 148.6
(2s); 128.3, 127.1 (2s); 126.3, 124.3 (2s); 123.8, 123.3 (2d); 118.0, 116.1 (2d); 111.3, 110.8 (2d); 108.1, 108.0 (2d);
59.5, 57.1 (2q); 56.2, 56.1 (2q); 55.3, 55.2 (2q); 49.4, 48.1 (2s); 45.1, 41.8 (2t); 41.1, 38.8 (2t); 35.1, 32.2 (2t). FAB-
‡
‡
HR-MS: 356.1509 ([M ‡ H] , C20H22O5N ; calc. 356.1498).
(Æ)-7-Acetyl-6,7,7a,8-tetrahydro-3,10,11-trimethoxy-dibenz[d,f]indol-2(5H)-one (2c). FT-IR: 2935s, 1630s,
1587s, 1514s, 1416s, 1249s, 1219s. 1H-NMR(CDCl 3, 400 MHz): Table 2. 13C-NMR(CDCl 3, 100 MHz): 181.0,
180.8 (2s); 169.9, 169.3 (2s); 157.6, 155.7 (2s); 151.9, 151.5 (2s); 151.4, 150.9 (2s); 148.6, 148.3 (2s); 128.4, 127.0
(2s); 125.3 (s); 123.6, 123.3 (2d); 117.3, 116.1 (2d); 111.1, 110.6 (2d); 108.1, 107.7 (2d); 60.2, 58.2 (2q); 56.0, 55.9
(2q); 55.3, 55.1 (2q); 48.4, 48.1 (2s); 45.8, 43.7 (2t); 41.0, 38.0 (2t); 33.8, 32.6 (2t); 22.9, 22.4 (2q). FAB-HR-MS:
‡
‡
370.1654 ([M ‡ H] , C21H24O5N ; calc. 370.1655).
(Æ)-Glaucine (ˆ(Æ)-5,6,6a,7-tetrahydro-1,2,9,10-tetramethoxy-6-methyl-4H-dibenzo[de,g]quinoline; 1).
1H-NMR(CDCl 3, 400 MHz): 8.06 (s, HÀC(11)); 6.75 (s, HÀC(8)); 6.56 (s, HÀC(3)); 3.91 (s, MeOÀC(9));
3.88 (s, MeOÀC(10)); 3.86 (s, MeOÀC(2)); 3.64 (s, MeOÀC(1)), 2.53 (s, MeN). FAB-MS: 356 (100, [M ‡
‡
H] ), 154 (45), 136 (30).
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Received July 14, 2003