Efficient iron-mediated approach to pyrano[3,2-a]carbazole alkaloids - First total syntheses of O-methylmurrayamine A and 7-methoxymurrayacine, first asymmetric synthesis and assignment of the absolute configuration of (-)-trans-dihydroxygirinimbine

Article abstract of DOI:10.1039/c0ob01088j

Iron-mediated oxidative cyclisation provides an efficient approach to pyrano[3,2-a]carbazole alkaloids. Thus, improved routes to girinimbine and murrayacine as well as the first total syntheses of O-methylmurrayamine A and 7-methoxymurrayacine are reporte

Full text of DOI:10.1039/c0ob01088j

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H.-J. Knölker et al.
Efficient iron-mediated approach to
pyrano[3,2-a]carbazole alkaloids
1477-0520(2011)9:7;1-B

Organic &
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Efficient iron-mediated approach to pyrano[3,2-a]carbazole alkaloids—first
total syntheses of O-methylmurrayamine A and 7-methoxymurrayacine, first
asymmetric synthesis and assignment of the absolute configuration of
(-)-trans-dihydroxygirinimbine†‡
Konstanze K. Gruner,a Thomas Hopfmann,a Kazuhiro Matsumoto,b Anne Ja¨ger,a Tsutomu Katsukib and
Hans-Joachim Kno¨lker*a
Received 25th November 2010, Accepted 5th January 2011
DOI: 10.1039/c0ob01088j
Iron-mediated oxidative cyclisation provides an efficient
approach to pyrano[3,2-a]carbazole alkaloids. Thus, im-
proved routes to girinimbine and murrayacine as well as
the first total syntheses of O-methylmurrayamine A and 7-
methoxymurrayacine are reported. Asymmetric epoxidation
of girinimbine led to (-)-trans-dihydroxygirinimbine and the
assignment of its absolute configuration.
(1) was the first pyrano[3,2-a]carbazole alkaloid isolated from
natural sources, by Chakraborty et al. from the stem bark and by
Joshi et al. from the leaves of Murraya koenigii.3,4 The structural
assignment of girinimbine (1) was based on spectroscopic studies
and chemical transformations.3,4
Further natural sources for girinimbine (1) are the roots
of Clausena heptaphylla as well as the root bark of Murraya
euchrestifolia.5,6 More recently, girinimbine (1) was shown to
exhibit antitumor activity.7 Murrayacine (2) has been isolated
by Chakraborty et al. from two different natural sources, Mur-
raya koenigii3c,8 and Clausena heptaphylla.9 The isolation of O-
methylmurrayamine A (3) from the leaves of Murraya koenigii
has been reported by Nakatani et al. only in 2003.10 Prior to
its isolation from natural sources, this alkaloid was obtained by
semisynthesis via O-methylation of natural murrayamine A.11 7-
Methoxymurrayacine (4) was obtained by Lange et al. in 1990
from the roots of Murraya siamensis.12 In 1985, Furukawa et al.
described the isolation of (-)-trans-dihydroxygirinimbine ((-)-5)
from the roots of Murraya euchrestifolia.13 The structural assign-
ment was supported by epoxidation and subsequent hydrolysis
of natural girinimbine (1), which afforded ( )-5 along with ( )-
cis-dihydroxygirinimbine (( )-6).13 However, the absolute config-
uration of (-)-trans-dihydroxygirinimbine ((-)-5), which shows an
optical rotation of [a]D = -4.0 (MeOH), was not determined. The
isolation of cis-dihydroxygirinimbine (6) has not been reported
yet in the literature but was achieved by Furukawa and Ito in
2006.14 From 1.2 kg of dried roots of Murraya koenigii collected
in Bangladesh, they obtained 1.2 mg of cis-dihydroxygirinimbine
(6). Because 6 showed no optical rotation and due to the absence
of Cotton effects in the CD spectrum, it was concluded that this
natural product is a racemate.14
Pyrano[3,2-a]carbazole alkaloids are highly interesting because of
their structural features, from the biogenetic point of view and
due to their useful biological activities (Fig. 1).1,2 Girinimbine
Fig. 1 Naturally occurring pyrano[3,2-a]carbazole alkaloids.
aDepartment Chemie, Technische Universita¨t Dresden, Bergstrasse 66,
01069 Dresden, Germany. E-mail: hans-joachim.knoelker@tu-dresden.de;
Fax: +49 351-463-37030
The pharmacological potential of the pyrano[3,2-a]carbazole
alkaloids has led to a strong interest in their synthesis and induced
the development of several routes to girinimbine (1) as the parent
compound.2,15 So far, we have reported two different approaches to
girinimbine (1). The first route relied on a molybdenum-mediated
construction of the carbazole framework and opened the way
to the first total synthesis of racemic trans-dihydroxygirinimbine
bDepartment of Chemistry, Faculty of Science, Graduate School and Institute
for Advanced Study, Kyushu University, Hakozaki, Higashi-ku, Fukuoka
812-8581, Japan
† Part 94 of ‘Transition Metals in Organic Synthesis’; for Part 93, see:
ref. 1.
‡ Electronic supplementary information (ESI) available: 1H and 13C NMR
data of compounds 1–6 and HPLC results of 6. CCDC reference number
801747. For ESI and crystallographic data in CIF or other electronic
format see DOI: 10.1039/c0ob01088j
(( )-5).16 In our second synthesis, we have used
a
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palladium-catalysed oxidative cyclisation as the key-step
leading to euchrestifoline. This was subsequently converted to
girinimbine (1).17 In the present work, we describe an improved
route to pyrano[3,2-a]carbazole alkaloids using our iron-mediated
construction of the carbazole ring system.18 Moreover, we report
an asymmetric synthesis of (-)-trans-dihydroxygirinimbine ((-)-5)
and the assignment of the absolute configuration for the natural
product.
The structure of girinimbine (1) has been additionally confirmed
by an X-ray crystal structure determination (Fig. 2).¶
The tricarbonyliron-coordinated cyclohexadienylium salts 7a
and 7b are readily available on a large scale via the 1-azabutadiene-
catalysed complexation of the corresponding cyclohexadiene
followed by hydride abstraction (Scheme 1).19 Using the improved
procedure, which has been developed in the course of our
synthesis of euchrestifoline, the aminochromene 8 was prepared
in three steps and 70% overall yield starting from 2-methyl-5-
nitrophenol.17 Reaction of the complex salts 7a and 7b with the
aminochromene 8 in acetonitrile at room temperature afforded
regioselectively the corresponding iron complexes 9a and 9b
by electrophilic aromatic substitution. Previous work in our
laboratories has shown that iron-mediated oxidative cyclisations
with concomitant aromatisation leading to 2-oxygenated and 2,7-
dioxygenated carbazoles are achieved best by treatment with
iodine in pyridine at elevated temperature.20 Thus, oxidation of
the iron complexes 9a and 9b with iodine in pyridine at 90 ◦C
provided girinimbine (1) and O-methylmurrayamine A (3) in 61%
and 63% yield, respectively. Subsequent oxidation of 1 and 3 with
DDQ led to murrayacine (2) and 7-methoxymurrayacine (4).
Fig. 2 Molecular structure of girinimbine (1) in the crystal.
For the enantioselective synthesis of trans-dihydroxygirinimbine
(5), we envisaged an asymmetric catalytic epoxidation of the
corresponding chromene double bond of girinimbine (1). The
titanium–salan catalyst 11, which is prepared by reaction of
ligand 10 with titanium tetra(isopropoxide) in the presence of
water (Scheme 2), had already provided excellent results in
the asymmetric catalytic epoxidation of chromenes.21 Therefore,
the asymmetric epoxidation of girinimbine (1) was carried out
with hydrogen peroxide in dichloromethane at 0 ◦C in the
presence of 5 mol% of the titanium–salan catalyst 11 with
an (S,S)-configuration. However, after removal of the solvent,
chromatography on silica gel provided no epoxide but a 1 : 1
mixture of (-)-trans-dihydroxygirinimbine ((-)-5) ([a]2D0 = -2.0,
c = 1, MeOH) and (-)-cis-dihydroxygirinimbine ((-)-6) (both in
12% yield) along with more than 70% of recovered girinimbine
(1) (Scheme 3). Presumably, the diastereoisomeric diol mixture
is formed by opening of the initially formed epoxide 12 to an
intermediate benzylic cation followed by a non-diastereoselective
attack of water. Employment of a phosphate buffer (pH = 7.4),
conditions which are known to avoid in situ hydrolysis of the
epoxide,22 also led to the 1 : 1 mixture of the diols (-)-5 and
(-)-6. All attempts to improve the turnover by modification of
the reaction conditions (temperature, reaction time, amount of
catalyst 11) gave no improvement (yields were ranging from
8–13%). Although the yield was only moderate, it was obvi-
ous that epoxidation in the presence of the (S,S)-titanium–
salan catalyst 11 provided preferentially the natural enantiomer
of trans-dihydroxygirinimbine: (-)-5. Consequently, asymmetric
epoxidation using the enantiomeric titanium–salan catalyst with
Scheme 1 Synthesis of the pyrano[3,2-a]carbazoles 1–4. Reagents and
conditions: (a) 2.2 equiv. 8, MeCN, rt, a: 1.5 h, 95% 9a, b: 7.5 h, 94%
9b; (b) 3.0 equiv. iodine, pyridine, 90 ◦C, 6 h, a: 61% 1, b: 63% 3; (c) 2.2
equiv. DDQ, MeOH–THF–H2O (3 : 1 : 1), rt, 90 min, (R = H): 96% 2, (R =
OCH3): 93% 4.
Scheme 2 Preparation of the (S,S)-titanium–salan complex 11. Reagents
and conditions: (a) 1.2 equiv. (S,S)-salan ligand 10, 1.0 equiv. Ti(Oi-Pr)4,
CH2Cl2, rt, 1 h, then addition of a few drops of H2O; the resulting complex
11 was used in situ.
The structural assignments for the pyrano[3,2-a]carbazoles 1–4
were based on their spectroscopic data which are in full agreement
3–12
with those reported for the corresponding natural products.§
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Scheme 3 Asymmetric epoxidation of girinimbine (1) to (-)-5 and (-)-6
and transformation of (-)-5 into the (S)-Mosher ester 13. Reagents and
conditions: (a) 5 mol% titanium–salan catalyst 11, 1.1 equiv. H2O2, CH2Cl2,
0
◦C, 48 h, 12% (-)-5 (98% ee), 12% (-)-6 (98% ee); (b) 3.0 equiv.
Fig. 3 Chiral HPLC of trans-dihydroxygirinimbine (5) using a Nucleocel
d-RP column from Macherey-Nagel, dimension: 250 ¥ 4.6 mm, T =
(R)-(-)-MTPACl, 3.0 equiv. Et3N, cat. DMAP, THF, rt, 48 h, 74%.
◦
35 C, eluent: MeCN–H2O (65 : 35), rate: 0.8 mL min-1, l = 260 nm; (a)
( )-trans-dihydroxygirinimbine (( )-5); (b) (-)-trans-dihydroxygirinimbine
((-)-5).
the (R,R)-configuration afforded (+)-trans-dihydroxygirinimbine
((+)-5). The dihydroxygirinimbines (-)-5 and (-)-6 are unequivo-
cally characterised by their spectroscopic data,ꢀ which have been
compared with those of the natural products (for the spectroscopic
data of natural cis-dihydroxygirinimbine (6), see ESI‡).13,14
esters obtained from ( )-trans-dihydroxygirinimbine (( )-5)16 led
us to assign an S-configuration to the stereogenic center at the
homobenzylic position of 13 (see ESI‡). The R-configuration of
the stereogenic center at the benzylic position results from the trans
relationship of the two hydroxy groups in (-)-5. Both diastereoiso-
meric diols, (-)-5 and (-)-6, are presumably generated from the
intermediate epoxide 12 by cleavage of the benzylic C–O bond and
subsequent non-diastereoselective attack of water at the resulting
benzylic cation. Thus, the obtained (-)-cis-dihydroxygirinimbine
((-)-6) is assumed to have an (S,S)-configuration.
In conclusion, we have developed a highly efficient route to
pyrano[3,2-a]carbazole alkaloids. The iron-mediated synthesis
provides girinimbine (1) in 2 steps and 58% overall yield based
on the aminochromene 8 (previous routes: 2 steps and 11%
overall yield,16 3 steps and 26% overall yield17). Moreover, we have
improved the access to murrayacine (2) and described the first
total syntheses of O-methylmurrayamine A (3) (2 steps and 59%
overall yield based on 8) and 7-methoxymurrayacine (4) (3 steps
and 55% overall yield based on 8). Although in only moderate
yield, asymmetric epoxidation of girinimbine (1) affords (-)-trans-
dihydroxygirinimbine ((-)-5) in 98% ee. The absolute configuration
of the natural product has been assigned by the Mosher method.
We are indebted to Professor Hiroshi Furukawa and Pro-
fessor Chihiro Ito (Faculty of Pharmacy, Meijo University,
Nagoya, Japan) for communicating to us prior to publication
details of their isolation and the spectroscopic data of natural
The enantiomeric excess of our synthetic (-)-trans-dihydroxygi-
rinimbine ((-)-5) has been determined by chiral HPLC. A
complete base line separation of the two enantiomers of ( )-
trans-dihydroxygirinimbine (( )-5)16 has been achieved using a
Nucleocel reversed phase column and optimised parameters
(Fig. 3). It has been shown that our synthetic (-)-5 had an
enantiomeric excess of 98%. An alternative set of experimental
conditions for the chiral HPLC led to a separation of the two
enantiomers of cis-dihydroxygirinimbine (6) (see ESI‡). Thus, we
could confirm that the diastereoisomer (-)-6 was obtained in the
same enantiomeric excess of 98% ee. This observation supports
our hypothesis that both diastereoisomeric diols are generated by
a non-diastereoselective hydrolysis of the initially formed epoxide
12. Moreover, the optical rotation of [a]2D0 = -12.0 (c = 0.5, MeOH)
of our synthetic (-)-6 supports the assumption of Furukawa and
Ito that the natural product has been obtained as a racemate.14
Finally, we have assigned the absolute configuration of the nat-
ural product using the method described by Mosher.23 Reaction of
(-)-trans-dihydroxygirinimbine ((-)-5) with (R)-(-)-a-methoxy-a-
(trifluoromethyl)phenylacetyl chloride ((R)-(-)-MTPACl) led to a
regioselective monoacylation of the homobenzylic hydroxy group
and afforded the corresponding (S)-Mosher ester 13 (Scheme
3).** Comparison of the 1H NMR spectrum of compound
13 with that of the diastereoisomeric mixture of (S)-Mosher
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1
cis-dihydroxygirinimbine. We would like to thank B. Sc. Sebastian
Kutz for experimental support. H.-J. K. is grateful to the Japan
Society for the Promotion of Science (JSPS) for a fellowship.
992, 952, 875, 740, 710, 596 cm-1; H NMR (500 MHz, acetone-d6): d =
1.27 (s, 3 H), 1.55 (s, 3 H), 2.31 (s, 3 H), 3.80 (d, J = 8.0 Hz, 1 H), 4.96
(d, J = 8.0 Hz, 1 H), 7.13 (m, 1 H), 7.28 (m, 1 H), 7.56 (d, J = 8.1 Hz, 1
H), 7.77 (s, 1 H), 7.97 (d, J = 7.8 Hz, 1 H), 9.88 (br s, 1 H); 13C NMR and
DEPT (125 MHz, acetone-d6): d = 16.78 (CH3), 19.34 (CH3), 27.17 (CH3),
69.77 (CH), 77.12 (CH), 79.41 (C), 107.21 (C), 111.61 (CH), 116.88 (C),
118.24 (C), 119.32 (CH), 119.57 (CH), 121.33 (CH), 123.94 (C), 124.51
(CH), 138.86 (C), 140.69 (C), 150.25 (C); MS (EI): m/z (%) = 297 (M+,
67), 279 (11), 226 (18), 225 (100), 210 (11); anal. calc. for C18H19NO3: C,
72.21, H 6.44, N 4.71, found: C 73.06, H 6.66, N 5.14.
Notes and references
§ Spectroscopic data for girinimbine (1): Colourless crystals, mp 176 ◦C
(ref. 3a: 176 ◦C); UV (EtOH): l = 237, 287, 327, 342, 358, 384 nm; IR
(KBr): n = 3317, 2974, 1642, 1609, 1495, 1460, 1440, 1404, 1360, 1345,
1321, 1243, 1227, 1210, 1191, 1176, 1158, 1145, 1121, 1058, 1023, 882, 757,
742, 725, 689, cm-1; 1H NMR (500 MHz, CDCl3): d = 1.48 (s, 6 H), 2.33
(s, 3 H), 5.69 (d, J = 9.7 Hz, 1 H), 6.62 (d, J = 9.7 Hz, 1 H), 7.17 (t, J =
7.0 Hz, 1 H), 7.30 (t, J = 7.0 Hz, 1 H), 7.37 (d, J = 7.0 Hz, 1 H), 7.66
(s, 1 H), 7.87 (br s, 1 H), 7.90 (d, J = 7.0 Hz, 1 H); 13C NMR and DEPT
(125 MHz, CDCl3): d = 16.07 (CH3), 27.58 (2 CH3), 75.84 (C), 104.41 (C),
110.36 (CH), 116.71 (C), 117.21 (CH), 118.59 (C), 119.30 (CH), 119.46
(CH), 121.13 (CH), 123.88 (C), 124.23 (CH), 129.40 (CH), 134.78 (C),
139.42 (C), 149.77 (C); MS (EI): m/z (%) = 263 (M+, 26), 248 (100), 85
(15); HRMS: m/z calc. for C18H17NO (M+): 263.1310; found: 263.1288.
Spectroscopic data for murrayacine (2): Colourless crystals, mp 248–
250 ◦C (ref. 3c, 8, 9: 244–245 ◦C); UV (EtOH): l = 225, 242 (sh), 282,
302, 347 (sh), 364 nm; IR (ATR): n = 3217, 3156, 2955, 2921, 2853, 1663,
1635, 1602, 1575, 1474, 1453, 1408, 1374, 1352, 1331, 1233, 1198, 1186,
1160, 1118, 1047, 1012, 893, 854, 833, 735, 690, 655, 561 cm-1; 1H NMR
(500 MHz, CDCl3): d = 1.55 (s, 6 H), 5.80 (d, J = 9.9 Hz, 1 H), 6.62 (d,
J = 9.9 Hz, 1 H), 7.23–7.29 (m, 1 H), 7.36–7.40 (m, 2 H), 7.97 (d, J =
7.8 Hz, 1 H), 8.15 (br s, 1 H), 8.42 (s, 1 H), 10.49 (s, 1 H); 13C NMR
and DEPT (125 MHz, CDCl3): d = 27.65 (2 CH3), 77.56 (C), 104.12 (C),
110.71 (CH), 116.15 (CH), 118.17 (C), 118.66 (C), 119.82 (CH), 120.26
(CH), 120.93 (CH), 124.05 (C), 125.95 (CH), 130.12 (CH), 140.03 (C),
140.20 (C), 154.79 (C), 189.24 (CHO); MS (EI): m/z (%) = 277 (M+, 13),
262 (100), 260 (25), 204 (19); anal. calc. for C18H15NO2: C 77.96, H 5.45,
N 5.05, found: C 77.93, H 5.34, N 4.91.
Spectroscopic data for O-methylmurrayamine A (3): Colourless crystals,
mp 253–255 ◦C (ref. 11: 232–233 ◦C); UV (EtOH): l = 220, 241, 244 (sh),
284 (sh), 293, 341, 357 (sh) nm; IR (KBr): n = 3387, 3007, 2974, 2925, 1645,
1626, 1452, 1433, 1270, 1213, 1195, 1159, 1060, 1030, 1014, 831 cm-1; 1H
NMR (500 MHz, acetone-d6): d = 1.48 (s, 6 H), 2.30 (s, 3 H), 3.86 (s, 3 H),
5.78 (d, J = 9.8 Hz, 1 H), 6.77 (dd, J = 8.5 Hz, 2.2 Hz, 1 H), 6.90 (d, J =
9.8 Hz, 1 H), 6.96 (d, J = 2.2 Hz, 1 H), 7.63 (s, 1 H), 7.82 (d, J = 8.5 Hz,
1 H), 10.15 (br s, 1 H); 13C NMR and DEPT (125 MHz, acetone-d6): d =
16.17 (CH3), 27.81 (2 CH3), 55.64 (CH3), 76.29 (C), 95.60 (CH), 105.46
(C), 108.23 (CH), 117.71 (C), 118.06 (C), 118.23 (C), 118.62 (CH), 120.49
(CH), 120.96 (CH), 129.90 (CH), 136.18 (C), 142.26 (C), 149.43 (C), 159.02
(C); MS (EI): m/z (%) = 293 (M+, 32), 278 (65), 263 (31), 248 (100), 211
(14), 189 (12), 170 (18); HRMS: m/z calc. for C19H19NO2 (M+): 293.1416;
found: 293.1405.
Spectroscopic data for (-)-cis-dihydroxygirinimbine ((-)-6): Colourless
◦
crystals, mp 160 C; [a]2D0 = -12.0 (c = 0.5, MeOH); UV (MeOH): l =
214, 233 (sh), 239, 254 (sh), 260, 267 (sh), 304, 333 nm; IR (ATR): n =
3436, 3380, 2978, 2909, 1660, 1630, 1609, 1578, 1491, 1472, 1457, 1442,
1431, 1379, 1306, 1206, 1163, 1146, 1102, 1064, 1038, 1014, 996, 933, 920,
902, 875, 845, 795, 743, 728, 604, 581, cm-1; 1H NMR (500 MHz, acetone-
d6): d = 1.37 (s, 3 H), 1.55 (s, 3 H), 2.30 (s, 3 H), 3.87 (br d, J = 4.7 Hz,
1 H), 4.19 (m, 1 H), 4.29 (m, 1 H), 5.22 (br d, J = 4.7 Hz, 1 H), 7.13 (m,
1 H), 7.28 (m, 1 H), 7.57 (d, J = 8.1 Hz, 1 H), 7.77 (s, 1 H), 7.97 (d, J =
7.7 Hz, 1 H), 9.83 (br s, 1 H); 13C NMR and DEPT (125 MHz, acetone-
d6): d = 16.83 (CH3), 24.48 (2 CH3), 65.21 (CH), 71.83 (CH), 78.38 (C),
105.70 (C), 111.64 (CH), 116.71 (C), 118.28 (C), 119.33 (CH), 119.53 (CH),
121.27 (CH), 124.09 (C), 124.44 (CH), 139.77 (C), 140.77 (C), 150.53 (C);
MS (EI): m/z (%) = 297 (M+, 73), 279 (20), 226 (33), 225 (100), 210 (18);
HRMS: m/z calc. for C18H19NO3: 297.1365; found: 297.1347.
1
** Spectroscopic data for the (S)-Mosher ester 13: Yellow oil; H NMR
(600 MHz, CDCl3): d = 1.17 (s, 3 H), 1.34 (s, 3 H), 2.29 (s, 3 H), 3.64 (s, 3
H), 5.10 (br d, J = 8.3 Hz, 1 H), 5.36 (d, J = 8.8 Hz, 1 H), 7.17 (t, J = 7.7
Hz, 1 H), 7.32 (t, J = 8.0 Hz, 1 H), 7.39 (d, J = 8.0 Hz, 1 H), 7.45–7.47 (m,
3 H), 7.66–7.68 (m, 2 H), 7.74 (s, 1 H), 7.92 (d, J = 7.7 Hz, 1 H), 8.72 (br
s, 1 H); 13C NMR and DEPT (150 MHz, CDCl3): d = 16.45 (CH3), 19.47
(CH3), 26.25 (CH3), 55.57 (CH3), 68.63 (CH), 77.33 (C), 79.84 (CH), 84.86
2
(q, JC,F = 31.6 Hz, C), 104.24 (C), 110.57 (CH), 116.95 (C), 118.42 (C),
119.36 (CH), 119.41 (CH), 121.99 (CH), 123.05 (C), 124.48 (CH), 127.44
(2 CH), 128.57 (2 CH), 129.88 (CH), 131.99 (C), 137.20 (C), 139.43 (C),
148.83 (C), 166.99 (C O), signal for the CF3 group not visible; 19F NMR
(282 MHz, CDCl3): d = -71.01 (s).
1 R. Forke, K. K. Gruner, K. E. Knott, S. Auschill, S. Agarwal, R.
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Spectroscopic data for 7-methoxymurrayacine (4): Yellow plates, mp 237–
239 ◦C (from MeOH–THF, 8 : 1) (ref. 12: 211–213 ◦C); UV (EtOH): l =
225, 235, 247 (sh), 290 (sh), 304, 337 (sh), 354 nm; IR (KBr): n = 3188,
2924, 2856, 1659, 1633, 1601, 1578, 1426, 1202, 1157, 1052, 814 cm-1; 1H
NMR (500 MHz, DMSO-d6): d = 1.49 (s, 6 H), 3.84 (s, 3 H), 5.93 (d, J =
9.9 Hz, 1 H), 6.80 (dd, J = 8.5 Hz, 2.3 Hz, 1 H), 6.93 (d, J = 9.9 Hz, 1 H),
6.94 (s, 1 H), 7.99 (d, J = 8.5 Hz, 1 H), 8.21 (s, 1 H), 10.35 (s, 1 H), 11.66
(s, 1 H); 13C NMR and DEPT (125 MHz, DMSO-d6): d = 27.21 (2 CH3),
55.32 (CH3), 76.97 (C), 95.32 (CH), 104.12 (C), 108.43 (CH), 116.66 (C),
116.79 (CH), 117.39 (C), 117.83 (CH), 117.86 (C), 121.08 (CH), 130.08
(CH), 140.71 (C), 142.16 (C), 153.18 (C), 158.64 (C), 187.96 (CHO); MS
(EI): m/z (%) = 307 (M+, 60), 292 (100), 264 (7); HRMS: m/z calc. for
C19H17NO3 (M+): 307.1208; found: 307.1197.
7 C.-B. Cui, S.-Y. Yan, B. Cai and X.-S. Yao, J. Asian Nat. Prod. Res.,
2002, 4, 233.
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11 T.-S. Wu, Phytochemistry, 1991, 30, 1048.
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¶ Crystal data for girinimbine (1): C18H17NO, crystal size: 0.42 ¥ 0.17 ¥
3
-1
˚
0.09 mm , M = 263.33 g mol , monoclinic, space group: Cc, l = 0.71073 A,
◦
˚
a = 11.960(2), b = 16.344(3), c = 7.655(2) A, b = 109.03(3) , V = 1414.6(5)
3
-3
-1
˚
A , Z = 4, rc = 1.236 g cm , m = 0.076 mm , T = 198(2) K, q range = 3.07–
28.00◦; reflections collected: 24148, independent: 3367 (Rint = 0.0753). The
structure was solved by direct methods and refined by full-matrix least-
13 H. Furukawa, T.-S. Wu and C.-S. Kuoh, Heterocycles, 1985, 23, 1391.
14 H. Furukawa and C. Ito, unpublished results.
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3902.
squares on F2; R1 = 0.0375, wR2 = 0.0747 [I > 2s(I)]; maximal residual
-3
˚
electron density: 0.127e A . CCDC 801747.
ꢀ Spectroscopic data for (-)-trans-dihydroxygirinimbine ((-)-5): Colourless
crystals, mp 170–172◦C;[a]D20 = -2.0 (c = 1, MeOH) (ref. 13:mp 189–190 ◦C;
[a]D = -4.0, MeOH); UV (MeOH): l = 216, 42, 254 (sh), 260, 304, 333
nm; IR (ATR): n = 3488, 3369, 2977, 2918, 2851, 1630, 1609, 1576, 1460,
1436, 1390, 1372, 1345, 1308, 1211, 1179, 1140, 1114, 1070, 1020, 1003,
2060 | Org. Biomol. Chem., 2011, 9, 2057–2061
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The Royal Society of Chemistry 2011
©

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23 J. A. Dale and H. S. Mosher, J. Am. Chem. Soc., 1973, 95, 512.
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The Royal Society of Chemistry 2011
Org. Biomol. Chem., 2011, 9, 2057–2061 | 2061
©