LETTER
First Total Synthesis of Methyl 6-Methoxycarbazole-3-carboxylate
271
(
9) Chakravarty, A. K.; Sarkar, T.; Masuda, K.; Shiojima, K.
Phytochemistry 1999, 50, 1263.
10) Rastogi, K.; Kapil, R. S.; Popli, S. P. Phytochemistry 1980,
9, 945.
(27) Pure glycomaurrol (5) was obtained by preparative HPLC on
a Vydac C8 50 mm column (gradient elution with 50 mL/min
(
(
(
(
MeCN–H O, 30–60% MeCN in 30 min).
2
1
Glycomaurrol (5): colorless crystals; mp 141 °C. UV
(MeOH): lmax = 257, 269, 292 (sh), 301, 350, 362 (sh) nm.
IR (ATR): n = 3409, 3214, 2917, 1589, 1512, 1499, 1476,
1442, 1390, 1349, 1309, 1282, 1267, 1225, 1166, 1148,
11) Li, W.-S.; McChesney, J. D.; El-Feraly, F. S.
Phytochemistry 1991, 30, 343.
12) Adesina, S. K.; Olugbade, T. A.; Akinwusi, D. D.;
Bergenthal, D. Pharmazie 1997, 52, 720.
13) (a) Mukherjee, S.; Mukherjee, M.; Ganguly, S. N.
Phytochemistry 1983, 22, 1064. (b) Bhattacharyya, P.;
Sarkar, T.; Chakraborty, A.; Chowdhury, B. K. Indian J.
Chem., Sect. B: Org. Chem. Incl. Med. Chem. 1984, 23, 49.
14) Wu, S.-L.; Li, W.-S. Chin. Pharm. J. 1999, 51, 227.
15) Kumar, V.; Reisch, J.; Wickramasinghe, A. Aust. J. Chem.
–
1
1100, 1069, 1030, 954, 871, 850, 797, 739, 694, 648 cm .
1
H NMR (500 MHz, acetone-d ): d = 1.72 (d, J = 1.2 Hz, 3
6
H), 1.98 (s, 3 H), 2.51 (s, 3 H), 4.01 (d, J = 6.5 Hz, 2 H), 5.37
(t, J = 6.5 Hz, 1 H), 7.03 (d, J = 8.5 Hz, 1 H), 7.19 (d, J = 8.5
Hz, 1 H), 7.20 (m, 1 H), 7.37 (d, J = 8.2 Hz, 1 H), 7.70 (s, 1
1
3
(
(
H), 7.95 (s, 1 H), 9.94 (br s, 1 H). C NMR and DEPT (125
MHz, acetone-d ): d = 18.34 (CH ), 21.67 (CH ), 25.83
6
3
3
1989, 42, 1375.
(CH ), 26.24 (CH ), 109.21 (CH), 111.09 (CH), 115.52
3 2
(
16) Ma, C.; Case, R. J.; Wang, Y.; Zhang, H.-J.; Tan, G. T.;
Hung, N. V.; Cuong, N. M.; Franzblau, S. G.; Soejarto, D.
D.; Fong, H. H. S.; Pauli, G. F. Planta Med. 2005, 71, 261.
17) Ito, C.; Furukawa, H. Chem. Pharm. Bull. 1990, 38, 1548.
18) (a) Chakraborty, D. P.; Das, K. C.; Chowdhury, B. K. Sci.
Cult. 1966, 32, 245. (b) Chakraborty, D. P.; Das, K. C.;
Chowdhury, B. K. Chem. Ind. 1966, 1684. (c) Carruthers,
W. J. Chem. Soc., Chem. Commun. 1966, 272.
(CH), 122.15 (C), 122.97 (C), 123.29 (CH), 124.05 (CH),
124.34 (C), 126.87 (CH), 127.59 (C), 131.86 (C), 136.06
(C), 140.13 (C), 148.19 (C). MS (100 °C): m/z (%) = 265
+
(
(
(100) [M ], 210 (71), 209 (87), 181 (14), 180 (19), 167 (9).
+
HRMS: m/z calcd for C H NO [M ]: 265.1467; found:
1
8
19
265.1454.
(28) Crystal data for the bromocarbazole 12: C H BrNO ,
1
4
10
2
M = 304.14, monoclinic, space group: P2
/c, a = 19.570(4),
1
(
d) Bhattacharyya, P.; Mitra, A. R.; Chakraborty, D. P. J.
b = 8.296(2), c = 7.360(2) Å, b = 94.77(3)°, V = 1190.8(5)
3
–3
–1
Indian Chem. Soc. 1976, 53, 321. (e) Bhattacharyya, P.;
Jash, S. S. Indian J. Chem., Sect. B: Org. Chem. Incl. Med.
Chem. 1986, 25, 1056. (f) Kudav, D. P.; Kulkarni, N. N.;
Hosangadi, B. D. J. Chem. Res., Synop. 1994, 266.
19) (a) Anwer, F.; Masaldan, A. S.; Kapil, R. S.; Popli, S. P.
Indian J. Chem. 1973, 11, 1314. (b) Chowdhury, B. K.;
Saha, C. Indian J. Chem., Sect. B: Org. Chem. Incl. Med.
Chem. 1994, 33, 892.
Å , Z = 4, D = 1.696 g cm , m = 3.444 mm , T = 198(2) K,
c
l = 0.71073 Å, q range: 3.13–30.00°, 29544 reflections
collected, 3454 independent (Rint = 0.0629), 168 parameters.
The structure was solved by direct methods and refined by
2
(
full-matrix least-squares on F ; final R indices [I > 2s(I)]:
R = 0.0405, wR = 0.0761; maximal residual electron
1 2
–
3
density: 0.598 e Å . CCDC-628163 contains the
supplementary crystallographic data for this paper. These
data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
(
(
20) Iwao, M.; Takehara, H.; Furukawa, S.; Watanabe, M.
Heterocycles 1993, 36, 1483.
21) (a) Fröhner, W.; Krahl, M. P.; Reddy, K. R.; Knölker, H.-J.
Heterocycles 2004, 63, 2393. (b) Knölker, H.-J.; Reddy, K.
R. In Selected Methods for Synthesis and Modification of
Heterocycles – The Chemistry and Biological Activity of
Natural Indole Systems, Part 1, Vol. 4; Kartsev, V. G., Ed.;
ICSPF Press: Moscow, 2005, 166.
(29) Pure micromeline (6) was obtained by preparative HPLC on
a Vydac C8 50 mm column (gradient elution with 50 mL/min
MeCN–H O, 30–60% MeCN in 30 min).
2
Micromeline (6): colorless crystals; mp 205–206 °C. UV
(MeOH): lmax = 231, 252, 276 (sh), 278, 281, 295 (sh), 300,
340 nm. IR (ATR): n = 3156, 2963, 2911, 2854, 2740, 1663,
1649, 1629, 1603, 1566, 1522, 1464, 1446, 1371, 1310,
1291, 1271, 1228, 1202, 1181, 1164, 1120, 1063, 1028, 958,
(
(
22) (a) Hartwig, J. F. Angew. Chem. Int. Ed. 1998, 37, 2046.
(
2
b) Muci, A. R.; Buchwald, S. L. Top. Curr. Chem. 2002,
19, 131.
–
1 1
23) (a) Åkermark, B.; Eberson, L.; Jonsson, E.; Petersson, E. J.
Org. Chem. 1975, 40, 1365. (b) Miller, R. B.; Moock, T.
Tetrahedron Lett. 1980, 21, 3319. (c) Furukawa, H.; Ito, C.;
Yogo, M.; Wu, T.-S. Chem. Pharm. Bull. 1986, 34, 2672.
899, 883, 851, 811, 792, 717, 663 cm . H NMR (500 MHz,
acetone-d ): d = 1.72 (d, J = 1.1 Hz, 3 H), 2.03 (s, 3 H), 4.07
6
(d, J = 6.4 Hz, 2 H), 5.36 (t, J = 6.4 Hz, 1 H), 7.15 (d, J = 8.5
Hz, 1 H), 7.33 (d, J = 8.5 Hz, 1 H), 7.63 (d, J = 8.5 Hz, 1 H),
7.95 (dd, J = 8.5, 1.4 Hz, 1 H), 8.03 (br s, 1 H), 8.69 (s, 1 H),
(d) Knölker, H.-J.; O’Sullivan, N. Tetrahedron 1994, 50,
1
3
1
0893. (e) Knölker, H.-J.; Fröhner, W.; Reddy, K. R.
10.09 (s, 1 H), 10.70 (br s, 1 H). C NMR and DEPT (125
MHz, acetone-d ): d = 18.43 (CH ), 25.80 (CH ), 26.19
(CH ), 110.07 (CH), 111.79 (CH), 116.63 (CH), 122.76 (C),
Synthesis 2002, 557. (f) Knölker, H.-J.; Reddy, K. R.
Heterocycles 2003, 60, 1049. (g) Knölker, H.-J.; Knöll, J.
Chem. Commun. 2003, 1170.
6
3
3
2
123.26 (C and CH), 124.05 (C), 126.63 (CH), 127.40 (CH),
129.39 (C), 132.83 (C), 136.07 (C), 145.38 (C), 149.40 (C),
(
24) The preparation of compound 10 using a Pd(0)-catalyzed
+
amination has been reported previously, albeit in lower yield
(
Chem. 2003, 68, 8416.
191.85 (CHO). MS (150 °C): m/z (%) = 279 (93) [M ], 224
77%): Urgaonkar, S.; Xu, J.-H.; Verkade, J. G. J. Org.
(81), 223 (100), 208 (7), 195 (13), 194 (10), 183 (11), 167
+
(11). HRMS: m/z calcd for C18
H17NO
[M ]: 279.1259;
2
(
(
25) Corey, E. J.; Gilman, N. W.; Ganem, B. E. J. Am. Chem. Soc.
found: 279.1262. Anal. Calcd (%) for C18
H17NO
2
: C, 77.40;
1
968, 90, 5616.
H, 6.13; N, 5.01. Found: C, 77.50; H, 6.22; N, 5.03.
(30) Röhrkasten, R.; Konrad, M. In Methoden der Organischen
Chemie (Houben-Weyl), Vol. E6b; Kreher, R. P., Ed.;
Thieme: Stuttgart, 1994, 94.
(31) Amberlyst 15 from Fluka (art. 06423).
(32) A separation of the two isomers 7 and 15 was achieved by
preparative HPLC on a Vydac C8 30 mm column (gradient
26) (a) Wilke, G.; Bogdanovic, B.; Hardt, P.; Heimbach, P.;
Keim, W.; Kröner, M.; Oberkirch, W.; Tanaka, K.;
Steinrücke, E.; Walter, D.; Zimmermann, H. Angew. Chem.,
Int. Ed. Engl. 1966, 5, 151. (b) Corey, E. J.; Semmelhack,
M. F. J. Am. Chem. Soc. 1967, 89, 2755. (c) Plieninger, H.;
Sirowej, H. Chem. Ber. 1971, 104, 2027. (d) Inoue, S.;
Yamaguchi, R.; Saito, K.; Sato, K. Bull. Chem. Soc. Jpn.
elution with 40 mL/min MeCN–H
min).
O, 30–46% MeCN in 32
2
1974, 47, 3098. (e) Billington, D. C. Chem. Soc. Rev. 1985,
14, 93.
Eustifoline-D (7): colorless crystals; mp 156 °C. UV
(
MeOH): lmax = 253, 260 (sh), 268, 298, 310, 339, 354 nm.
Synlett 2007, No. 2, 268–272 © Thieme Stuttgart · New York