A New Approach to the Total Synthesıs of (±)-Nordasycarpıdone by Rıng-closure wıth Tetrachloro-1,4-benzoquınone

Nesimi Uludag


A new synthetic route for the  (±)-nordasycarpidone was achieved in five steps with an overall yield of  41%. This route involves  ring closure and formation of 5 which has a  methanoazocino[4,3-b]indole skeleton in the key step. The reaction also involved a cyclization reaction of  tetrahydrocarbazole with a monoalkyl nitrile side chain at the C-2 position, and this reaction was mediated by tetrachloro-1,4-benzoquinone (TCB). The central step in the synthesis was  the closure of the D-ring of the intra-molecular structure and the addition of amine, which resulted in an aza-tetracyclic substructure that contained the ABCD-ring of the strychnos alkaloid family.


dasycarpidone; uleine; nordasycarpidone; 1,5-methanoazacino[4,3-b]indole

Full Text:



F. Tang, M. G. Banwell, A. C. Willis, Palladium-catalyzed Ullmann Cross-Coupling/Tandem reductive cyclization route to key members of the uleine alkaloid family, J. Org. Chem. 81, 2950–2957 (2016).

DOI: https://doi.org/10.1021/acs.joc.6b00240

R. Akdag, Y. Ergun, Y. A new synthetic route to the synthesis of nordasycarpidone derivatives, J. Heterocycl. Chem. 44, 863–866 (2007).

DOI: https://doi.org/10.1002/jhet.5570440418

M. Amat, S. Hadida, G. Pshenichnyi., J. Bosch, Palladium(0)-catalyzed heteroarylation of 2- and 3-indolylzinc derivatives. An efficient general method for the preparation of (2-pyridyl)indoles and their application to indole alkaloid synthesis, J. Org. Chem. 62, 3158–3175 (1997).

DOI: https://doi.org/10.1021/jo962169u

J. Gracia, N. Casamitjana, J. Bonjoch, Total synthesis of uleine-type and strychnos alkaloids through a common intermediate, J. Org. Chem. 59, 3939–3951 (1994). DOI: https://doi.org/10.1021/jo00093a028

J. Bonjoch, N. Casamitjana, J. Gracia, A stereoselective total synthesis of dasycarpidan alkaloids: (±)-dasycarpidone, (±)-dasycarpidol and (±)-nordasycarpidone, J. Chem. Soc. Chem. Commun. 23, 1687–1688 (1991).

DOI: https://doi.org/10.1039/C39910001687

T. P. C. Chierrito, A. C. C. Aguiar, I. M. de Andrade, I. P. Ceravlolo, R. A. C. Gonçalves, A. J. B. de Oliveria, A. U. Krettli, Anti-malarial activity of indole alkaloids isolated from Aspidosperma olivaceum, Malar. J. 13, 142–151 (2014).

DOI: https://doi.org/10.1186/1475-2875-13-142

E. C. Miranda, S. Blechert, S. Gilbertin, Ein neuer Indolalkaloidtyp, Tetrahedron Lett. 23, 5395–5398 (1982).

DOI: https://doi.org/10.1016/0040-4039(82)80139-1

A. Jackson, N. D. V. Wilson, A. J. Gaskel, J. J. A. Joule, The syntheses of (±)-dasycarpidone, (±)-3-epi-dasy¬carpidone, (±)-uleine and (±)-3-epi-uleine, J. Chem. Soc. C, 2738–2747 (1969).

DOI: https://doi.org/10.1039/J39690002738

T. Kametani, T. Suzuki, Syntheses of heterocyclic compounds. CCCXCIV. Total syntheses of (±)-dasycarpidone and (±)-3-epidasycarpidone. Formal total syntheses of (±)-uleine and (±)-3-epiuleine, J. Org. Chem. 36, 1291–1293 (1971).

DOI: https://doi.org/10.1021/jo00808a026

N. Uludag, T. Hökelek, S. Patır, A new approach to the total synthesis of (±)‐20‐epidasycarpidone, J. Heterocycl. Chem. 43, 585–591 (2006).

DOI: https://doi.org/10.1002/jhet.5570430310

N. Uludag, S. Patır, Studies on the synthesis of the azocino[4,3‐b]indole framework and related compounds, J. Heterocycl. Chem. 44, 1317–1322 (2007).

DOI: https://doi.org/10.1002/jhet.5570440613

N. Uludag, R. Yılmaz, O. Asutay, N. Colak, Facile synthesis of the azocino[4,3-b]indole framework of strychnopivotine and other Strychnos alkaloids, Chem. Heterocycl. Compd. 52, 196–199 (2016).

DOI: https://doi.org/10.1007/s10593-016-1860-4

L. J. Dolby, H. Biere, The total synthesis of (±)-da-sycarpidone and (±)-epidasycarpidone, J. Am. Chem. Soc. 90, 2699–2700 (1968).

DOI: https://doi.org/10.1021/ja01012a047

L. Micouin, A. Diez, J. Castells, D. Lopez, M. Rubiralta, J. C. Quirion, H. P. Husson, Synthetic applications of 2-(1,3-dithian-2-yl)indoles V1. Asym-metric synthesis of dasycarpidone-type indole alkaloids, Tetrahedron Lett. 36, 1693–1696 (1995).

DOI: https://doi.org/10.1016/0040-4039(95)00047-G

S. Patır, N. Uludag, A novel Synthetic route for the total synthesis of (±)-uleine, Tetrahedron, 65, 115–118 (2009). DOI: https://doi.org/10.1016/j.tet.2008.10.102

M. Amat, M. Perez, N. Llor, M. Martinelli, E. Molins, J. Bosch, Enantioselective formal synthesis of uleine alkaloids from phenylglycinol-derived bicyclic lactams. Chem. Commun. 35, 1602–1603 (2004).

DOI: https://doi.org/10.1039/B400987H

P. Forns, A. Diez, M. Rubiralta, X. Solans, M. Font-Bardia, Synthetic applications of 2-(1,3-dithian-2-yl)indoles VI.1 Synthesis of 20-epidasycarpidone, Tetrahedron, 52, 3563–3574 (1996).

DOI: https://doi.org/10.1016/0040-4020(96)00033-6

N. Uludag, M. Yakup, Concise Total Synthesis of 20-deethyl-4-demethyldasycarpidone, Org. Prep. Proc. Int. 47, 454–460 (2015).

DOI: https://doi.org/10.1080/00304948.2015.1088756

E. J. Corey, K. Shimoji, Magnesium and zinc-catalyzed thioketalization, Tetrahedron Lett. 24, 169–172 (1983).

DOI: https://doi.org/10.1016/S0040-4039(00)81357-X

J. Bosch, M. Rubiralta, A. Domingo, J. Bolos, A. Linares, C. Minguillon, M. Amat, J. Bonjoch, Synthetic applications of 2-cyano-1,2,3,6-tetrahydropyridines. 2. Synthesis of isodasycarpidone and related systems, the ervitsine skeleton and its benzo analog, J. Org. Chem. 50, 1516–1522 (1985).

DOI: https://doi.org/10.1021/jo00209a031

N. J. Cussans, S. V. Ley, D. H. R. Barton, Removal of thioacetal protecting groups by benzeneseleninic anhydride, J. Chem Soc. Perkin Trans. I, 1654–1657 (1980).

DOI: https://doi.org/10.1039/P19800001654

J. Málek, M. Černý, Reduction of organic compounds by alkoxyaluminohydrides, Synthesis, 5, 217–234 (1972).

DOI: https://doi.org/10.1055/s-1972–21858

C. Höfler, C. Rüchardt, Bimolecular formation of radicals by hydrogen transfer, on the mechanism of quinone dehydrogenations, Liebigs. Ann. 183–188 (1996). DOI: https://doi.org/10.1002/jlac.199619960206

Y. Zhang, C, Li, DDQ-mediated direct cross-dehydrogenative-coupling (CDC) between benzyl ethers and simple ketones, J. Am. Chem. Soc. 128, 4242–4243 (2006). DOI: https://doi.org/10.1021/ja060050p

W. Tu, P. E. Floreangic, Oxidative carbocation formation in macrocycles: Synthesis of the neopeltolide macrocycle, Angew. Chem. Int. Ed. 48, 4567–4571 (2009). DOI: https://doi.org/10.1002/anie.200901489

M. Amat, S. Hadida, N. Llor, S. Sathyanarayana, J. Bosc, Studies on the configurational stability of 3-(2-piperidyl)indoles, J. Org. Chem. 61, 3878–3882 (1996).

DOI: https://doi.org/10.1021/jo952251+

J. A. Joule, M. Ohashi, B. Gilbert, C. Djerassi, Alkaloids studies — LIII: The structures of nine new alkaloids from Aspidosperma dasycarpon A. DC. Tetrahedron, 21, 1717–1734 (1965).

DOI: https://doi.org/10.1016/S0040-4020(01)98642-9

M. C. Mollo, N. Gruber, J. E. Diaz, J. A. Bisceglia, L. R. Orelli, An efficient synthesis of N-alkyl-N-arylputrescines and cadaverines, Org. Prep. Proc. Int. 46, 444–452 (2014).

DOI: https://doi.org/10.1080/00304948.2014.944404

DOI: http://dx.doi.org/10.20450/mjcce.2020.1736


  • There are currently no refbacks.

Copyright (c) 2020 Nesimi Uludag

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.