Subscribe to RSS
DOI: 10.1055/s-2008-1077855
Transition Metals in Organic Synthesis, Part 85. [1] A General Approach to 1,6-Dioxygenated Carbazole Alkaloids - First Total Synthesis of Clausine G, Clausine I, and Clausine Z
Publication History
Publication Date:
11 June 2008 (online)
Abstract
Using the palladium-catalyzed construction of the carbazole framework, a highly efficient route to 1,6-dioxygenated carbazole alkaloids has been developed and applied to the total synthesis of clausenine, 6-methoxymurrayanine, clausenol, clausine G, clausine I, and clausine Z. The three latter natural products have been synthesized for the first time.
Key words
alkaloids - antibiotics - catalysis - cyclizations - palladium
- 1 Part 84:
Fröhner W.Reddy KR.Knölker H.-J. Heterocycles 2007, 74: 895 - For some comprehensive reviews, see:
-
2a
Knölker H.-J.Reddy KR. In The Alkaloids Vol. 65:Cordell GA. Academic Press; Amsterdam: 2008. p.1 -
2b
Knölker H.-J. Top. Curr. Chem. 2005, 244: 115 -
2c
Knölker H.-J.Reddy KR. Chem. Rev. 2002, 102: 4303 -
2d
Chakraborty DP. In The Alkaloids Vol. 44:Cordell GA. Academic Press; New York: 1993. p.257 -
2e
Chakraborty DP.Roy S. In Progress in the Chemistry of Organic Natural Products Vol. 57:Herz W.Grisebach H.Kirby GW.Steglich W.Tamm C. Springer; Wien: 1991. p.71 - For accounts, see:
-
3a
Pindur U. Chimia 1990, 44: 406 -
3b
Bergman J.Pelcman B. Pure Appl. Chem. 1990, 62: 1967 -
3c
Kawasaki T.Sakamoto M. J. Indian Chem. Soc. 1994, 71: 443 -
3d
Moody CJ. Synlett 1994, 681 -
3e
Hibino S.Sugino E. In Advances in Nitrogen Heterocycles Vol. 1:Moody CJ. JAI Press; Greenwich, CT: 1995. p.205 -
3f
Kirsch GH. Curr. Org. Chem. 2001, 5: 507 -
3g
Lemster T.Pindur U. Recent Res. Dev. Org. Bioorg. Chem. 2002, 5: 99 -
3h
Knölker H.-J. Curr. Org. Synth. 2004, 1: 309 -
3i
Fröhner W.Krahl MP.Reddy KR.Knölker H.-J. Heterocycles 2004, 63: 2393 - Recent contributions:
-
4a
Krahl MP.Jäger A.Krause T.Knölker H.-J. Org. Biomol. Chem. 2006, 4: 3215 -
4b
Yamabuki A.Fujinawa H.Choshi T.Tohyama S.Matsumoto K.Ohmura K.Nobuhiro J.Hibino S. Tetrahedron Lett. 2006, 47: 5859 -
4c
Bedford RB.Betham M. J. Org. Chem. 2006, 71: 9403 -
4d
Yamamoto M.Matsubara S. Chem. Lett. 2007, 36: 172 -
4e
Liu Z.Larock RC. Tetrahedron 2007, 63: 347 -
4f
Ackermann L.Althammer A. Angew. Chem. Int. Ed. 2007, 46: 1627 -
4g
Lebold TP.Kerr MA. Org. Lett. 2007, 9: 1883 -
4h
Watanabe T.Ueda S.Inuki S.Oishi S.Fujii N.Ohno H. Chem. Commun. 2007, 4516 -
4i
St. Jean Jr. DJ.Poon SF.Schwarzbach JL. Org. Lett. 2007, 9: 4893 -
4j
Liu C.-Y.Knochel P. J. Org. Chem. 2007, 72: 7106 -
4k
Naffziger MR.Ashburn BO.Perkins JR.Carter RG. J. Org. Chem. 2007, 72: 9857 - 5
Li W.-S.McChesney JD.El-Feraly FS. Phytochemistry 1991, 30: 343 - 6
Chakraborty A.Chowdhury BK.Bhattacharyya P. Phytochemistry 1995, 40: 295 -
7a
Wu T.-S.Huang S.-C.Wu P.-L.Teng C.-M. Phytochemistry 1996, 43: 133 -
7b
Wu T.-S.Huang S.-C.Wu P.-L. Phytochemistry 1996, 43: 1427 - 8
Potterat O.Puder C.Bolek W.Wagner K.Ke C.Ye Y.Gillardon F. Pharmazie 2005, 60: 637 -
9a
Lin G.Zhang A. Tetrahedron Lett. 1999, 40: 341 -
9b
Lin G.Zhang A. Tetrahedron 2000, 56: 7163 -
10a
Bernal P.Benavides A.Bautista R.Tamariz J. Synthesis 2007, 1943 -
10b
González-Romero C.Bernal P.Jiménez F.del Carmen Cruz M.Fuentes-Benites A.Benavides A.Bautista R.Tamariz J. Pure Appl. Chem. 2007, 79: 181 -
11a
Hartwig JF. Angew. Chem. Int. Ed. 1998, 37: 2046 -
11b
Muci AR.Buchwald SL. Top. Curr. Chem. 2002, 219: 131 -
12a
Åkermark B.Eberson L.Jonsson E.Pettersson E. J. Org. Chem. 1975, 40: 1365 -
12b
Miller RB.Moock T. Tetrahedron Lett. 1980, 21: 3319 -
12c
Furukawa H.Ito C.Yogo M.Wu T.-S. Chem. Pharm. Bull. 1986, 34: 2672 -
12d
Knölker H.-J.O’Sullivan N. Tetrahedron 1994, 50: 10893 -
12e
Knölker H.-J.Fröhner W.Reddy KR. Synthesis 2002, 557 -
12f
Knölker H.-J.Reddy KR. Heterocycles 2003, 60: 1049 -
12g
Knölker H.-J.Knöll J. Chem. Commun. 2003, 1170 - 13
Rizzacasa MA.Sargent MV. Aust. J. Chem. 1988, 41: 1087 - 14
Knölker H.-J.Wolpert M. Tetrahedron 2003, 59: 5317 - 16
Winterfeldt E. Synthesis 1975, 617 -
17a
Manganese dioxide (precipitated, active) from Merck (art. 805958).
-
17b
Knölker H.-J. J. Prakt. Chem. 1995, 337: 75 - 18
Charrier N.Demont E.Dunsdon R.Maile G.Naylor A.O’Brien A.Redshaw S.Theobald P.Vesey D.Walter D. Synthesis 2006, 3467 - 19
Choi TA.Czerwonka R.Fröhner W.Krahl MP.Reddy KR.Franzblau SG.Knölker H.-J. ChemMedChem 2006, 1: 812 - 20
Choi TA.Czerwonka R.Knöll J.Krahl MP.Reddy KR.Franzblau SG.Knölker H.-J. Med. Chem. Res. 2006, 15: 28
References and Notes
Characteristic Spectroscopic Data of the 1,6-Dioxygenated Carbazole Alkaloids 1-6.
Clausenine (1): colorless crystals; mp 149-150 °C (lit.
[6]
151 °C). UV (MeOH): λmax = 226, 241, 258 (sh), 287 (sh), 299, 340, 354 nm. IR (ATR): ν = 3385, 2955, 2918, 2852, 1619, 1581, 1505, 1486, 1459, 1451, 1437, 1394, 1304, 1268, 1207, 1145, 1129, 1035, 1025, 940, 838, 821, 800, 769 cm-1. 1H NMR (500 MHz, DMSO-d
6): δ = 2.45 (s, 3 H), 3.82 (s, 3 H), 3.95 (s, 3 H), 6.78 (s, 1 H), 6.97 (dd, J = 8.7, 2.4 Hz, 1 H), 7.33 (d, J = 8.7 Hz, 1 H), 7.46 (s, 1 H), 7.55 (d, J = 2.4 Hz, 1 H), 10.92 (br s, 1 H). 13C NMR and DEPT (125 MHz, DMSO-d
6): δ = 21.57 (CH3), 55.23 (CH3), 55.51 (CH3), 102.64 (CH), 107.53 (CH), 111.97 (CH), 112.31 (CH), 114.56 (CH), 122.75 (C), 123.48 (C), 127.45 (C), 128.56 (C), 134.68 (C), 145.33 (C), 152.80 (C). MS (EI): m/z (%) = 241 (91) [M+], 226 (100), 211 (11), 198 (20), 183 (7), 167 (9), 155 (17), 154 (14). Anal. Calcd (%) for C15H15NO2: C, 74.67; H, 6.27; N, 5.81. Found: C, 74.88; H, 6.36; N, 5.50.
6-Methoxymurrayanine (2): colorless crystals; mp 230-231 °C (lit.
[5]
231-233 °C). UV (MeOH): λmax = 240, 253, 277, 296, 337, 350 nm. IR (ATR): ν = 3138, 3010, 2921, 2852, 1655, 1628, 1608, 1578, 1496, 1466, 1437, 1360, 1327, 1305, 1262, 1239, 1217, 1185, 1139, 1105, 1031, 1023, 944, 844, 805, 782, 749, 705, 668 cm-1. 1H NMR (500 MHz, acetone-d
6): δ = 3.92 (s, 3 H), 4.08 (s, 3 H), 7.12 (dd, J = 8.8, 2.4 Hz, 1 H), 7.43 (d, J = 1.0 Hz, 1 H), 7.56 (d, J = 8.8 Hz, 1 H), 7.79 (d, J = 2.4 Hz, 1 H), 8.34 (d, J = 1.0 Hz, 1 H), 10.03 (s, 1 H), 10.83 (br s, 1 H). 13C NMR and DEPT (125 MHz, acetone-d
6): δ = 56.06 (CH3), 56.08 (CH3), 103.64 (CH), 103.78 (CH), 113.50 (CH), 116.86 (CH), 120.81 (CH), 124.44 (C), 124.87 (C), 130.71 (C), 135.45 (C), 135.80 (C), 147.27 (C), 155.60 (C), 191.72 (CHO). MS (EI): m/z (%) = 255 (100) [M+], 240 (96), 225 (10), 224 (11), 212 (13), 184 (8), 169 (8).
Clausine Z (6): colorless crystals; mp 151 °C (dec.). UV (MeOH): λmax = 226, 246, 279, 298, 342, 355 nm. IR (ATR): ν = 3219, 2922, 2853, 1657, 1579, 1457, 1327, 1196, 1136, 958, 851, 800, 711 cm-1. 1H NMR (500 MHz, DMSO-d
6): δ = 6.93 (dd, J = 8.6, 2.4 Hz, 1 H), 7.24 (d, J = 1.0 Hz, 1 H), 7.34 (d, J = 8.6 Hz, 1 H), 7.44 (d, J = 2.4 Hz, 1 H), 8.13 (d, J = 1.0 Hz, 1 H), 9.12 (br s, 1 H), 9.90 (s, 1 H), 10.29 (br s, 1 H), 11.41 (br s, 1 H). 13C NMR and DEPT (125 MHz, DMSO-d
6): δ = 104.93 (CH), 106.44 (CH), 112.42 (CH), 115.73 (CH), 118.88 (CH), 123.15 (C), 123.84 (C), 128.71 (C), 134.04 (C), 134.48 (C), 143.65 (C), 151.30 (C), 191.72 (CHO). MS (EI): m/z (%) = 227 (100) [M+], 226 (60), 198 (27), 197 (24), 170 (13), 169 (10). HRMS: m/z calcd for C13H9NO3 [M+]: 227.0582; found: 227.0573.
Clausine G (5): light yellow crystals; mp 145-147 °C (lit.
[7b]
>280 °C). UV (MeOH): λmax = 224, 241, 250, 268, 284, 325 (sh), 334, 349 nm. IR (ATR): ν = 3355, 2952, 2922, 2833, 1667, 1630, 1612, 1582, 1500, 1471, 1431, 1355, 1322, 1297, 1251, 1202, 1172, 1125, 1087, 1026, 1001, 916, 871, 828, 793, 765, 751, 723 cm-1. 1H NMR (500 MHz, acetone-d
6): δ = 3.88 (s, 3 H), 3.92 (s, 3 H), 7.08 (dd, J = 8.8, 2.5 Hz, 1 H), 7.52 (d, J = 8.8 Hz, 1 H), 7.55 (d, J = 1.1 Hz, 1 H), 7.77 (d, J = 2.5 Hz, 1 H), 8.37 (d, J = 1.1 Hz, 1 H), 9.04 (br s, 1 H), 10.45 (br s, 1 H). 13C NMR and DEPT (125 MHz, acetone-d
6): δ = 51.91 (CH3), 56.07 (CH3), 103.59 (CH), 111.10 (CH), 113.23 (CH), 115.71 (CH), 116.67 (CH), 121.96 (C), 124.94 (C), 124.98 (C), 134.35 (C), 136.09 (C), 143.46 (C), 155.26 (C), 168.01 (C=O). Anal. Calcd (%) for C15H13NO4: C, 66.41; H, 4.83; N, 5.16. Found: C, 66.43; H, 4.95; N, 4.76.
Clausenol (3): light yellow crystals; mp 191-192 °C (lit.
[6]
139 °C). UV (MeOH): λmax = 227, 242, 292 (sh), 299, 343, 357 nm. IR (ATR): ν = 3367, 3228, 2921, 2851, 1652, 1621, 1590, 1578, 1520, 1481, 1457, 1434, 1388, 1318, 1298, 1269, 1210, 1178, 1142, 1095, 1024, 1005, 988, 943, 871, 833, 796, 748 cm-1. 1H NMR (500 MHz, DMSO-d
6): δ = 2.37 (s, 3 H), 3.81 (s, 3 H), 6.61 (s, 1 H), 6.95 (dd, J = 8.7, 2.5 Hz, 1 H), 7.31 (s, 1 H), 7.32 (d, J = 8.7 Hz, 1 H), 7.51 (d, J = 2.5 Hz, 1 H), 9.59 (s, 1 H), 10.64 (br s, 1 H). 13C NMR and DEPT (125 MHz, DMSO-d
6): δ = 21.38 (CH3), 55.55 (CH3), 102.67 (CH), 110.92 (CH), 111.38 (CH), 111.91 (CH), 114.39 (CH), 123.00 (C), 124.00 (C), 127.45 (C), 128.47 (C), 134.74 (C), 142.88 (C), 152.68 (C).
Clausine I (4): colorless crystals; mp 222-223 °C (lit.
[7a]
222-224 °C). UV (MeOH): λmax = 225 (sh), 242, 255, 278, 296, 340 (sh), 354 nm. IR (ATR): ν = 3385, 2955, 2919, 2852, 1619, 1581, 1486, 1460, 1437, 1393, 1304, 1268, 1207, 1184, 1145, 1130, 1111, 1035, 1025, 940, 838, 821, 800, 769, 733, 712 cm-1. 1H NMR (500 MHz, acetone-d
6): δ = 3.92 (s, 3 H), 7.11 (dd, J = 8.8, 2.4 Hz, 1 H), 7.40 (d, J = 0.6 Hz, 1 H), 7.55 (d, J = 8.8 Hz, 1 H), 7.77 (d, J = 2.4 Hz, 1 H), 8.25 (d, J = 0.6 Hz, 1 H), 9.27 (s, 1 H), 9.98 (s, 1 H), 10.64 (br s, 1 H). 13C NMR and DEPT (125 MHz, acetone-d
6): δ = 56.05 (CH3), 103.66 (CH), 107.95 (CH), 113.46 (CH), 116.76 (CH), 119.60 (CH), 125.04 (C), 125.08 (C), 130.79 (C), 135.43 (C), 136.03 (C), 144.40 (C), 155.47 (C), 191.76 (CHO). MS (EI): m/z (%) = 241 (100) [M+], 240 (10), 226 (78), 198 (15). HRMS: m/z calcd for C14H11NO3 [M+]: 241.0739; found: 241.0735.