Efficient Synthesis of the Key Intermediate of Scopolamine by [4+3]
Cycloaddition Reaction

Xiuyuan      Duan; Qian      Wang; Muhammad      Shahab; Chaoqun      Liang; Gudong      Li; Guojun      Zheng

Abstract

Scopolamine, as an anticholinergic agent, plays a regulatory role in the peripheral nervous system. In this paper, 6,7-dehydrotropinone, which is the key intermediate of scopolamine, is synthesized in moderate yield through [4+3] cyclization reaction and Barton deoxygenation reaction. This route has good application prospects with mild reaction conditions, moderate yield, and simple operating procedures.

Keywords: Scopolamine, 6, 7-dehydrotropinone, [4+3] Cycloaddition reaction, Barton-McCombie deoxygenation, mild reaction conditions, better application perspective.

Graphical Abstract

[1]
Christen, P. Stud. Nat. Prod. Chem.,  2000, 22, 717-749.
 [http://dx.doi.org/10.1016/S1572-5995(00)80038-1]

[2]
Grynkiewicz, G.; Gadzikowska, M. Pharmacol. Rep.,  2008, 60(4), 439-463.
 [PMID:  18799813]

[3]
Sheehan, J.C.; Bloom, B.M. J. Am. Chem. Soc.,  1952, 74(15), 3825-3828.
 [http://dx.doi.org/10.1021/ja01135a032]

[4]
Noyori, R. J. Am. Chem. Soc.,  1978, 100, 1786-1791.
 [http://dx.doi.org/10.1021/ja00474a021]

[5]
Hodgson, D.M.; Paruch, E. Tetrahedron,  2004, 60(24), 5185-5199.
 [http://dx.doi.org/10.1016/j.tet.2004.04.047]

[6]
Paparin, J.L.; Crévisy, C.; Toupet, L.; Grée, R. Eur. J. Org. Chem.,  2000, 2000(23), 3909-3918.
 [http://dx.doi.org/10.1002/1099-0690(200012)2000:23<3909:AID-EJOC3909>3.0.CO;2-R]

[7]
Nocquet, P.A.; Opatz, T. Eur. J. Org. Chem.,  2016, 2016(6), 1156-1164.
 [http://dx.doi.org/10.1002/ejoc.201501430]

[8]
Shibata, M.; Fuchigami, R.; Kotaka, R.; Namba, K.; Tanino, K. Tetrahedron,  2015, 71(26-27), 4495-4499.
 [http://dx.doi.org/10.1016/j.tet.2015.02.071]

[9]
Colomer, I.; Haughey, M. B.; Chamberlain, A. Nat. Rev. Chem.,  2017, 1, 0088.

[10]
Colomer, I. ACS Catal.,  2020, 10(11), 6023-6029.
 [http://dx.doi.org/10.1021/acscatal.0c00872]

[11]
Ge, H.M.; Zhang, L.D.; Tan, R.X.; Yao, Z.J. J. Am. Chem. Soc.,  2012, 134(30), 12323-12325.
 [http://dx.doi.org/10.1021/ja305261h] [PMID:  22799615]

[12]
Herrmann, J.M.; König, B. Eur. J. Org. Chem.,  2013, 2013(31), 7017-7027.
 [http://dx.doi.org/10.1002/ejoc.201300657]

[13]
Lee, E.H.; Cho, D.H.; Satyender, A.; Jang, D.O. Tetrahedron Lett.,  2011, 52(51), 6927-6929.
 [http://dx.doi.org/10.1016/j.tetlet.2011.10.063]

[14]
OkJang. D.; Hyan, C.D.; Kim. J. Synth. Commun.,  1998, 28(19), 3559-3565.
 [http://dx.doi.org/10.1080/00397919808004902]

[15]
Ohwada, T. J. Org. Chem.,  2018, 83, 13063-13079.
 [http://dx.doi.org/10.1021/acs.joc.8b01756] [PMID:  30284439]

[16]
Johnson, R.E.; Ree, H.; Hartmann, M.; Lang, L.; Sawano, S.; Sarpong, R. J. Am. Chem. Soc.,  2019, 141(6), 2233-2237.
 [http://dx.doi.org/10.1021/jacs.8b13388] [PMID:  30702879]

[17]
McCombie, S.W.; Quiclet, S.B.; Zard, S.Z. Tetrahedron,  2018, 74(38), 4969-4979.
 [http://dx.doi.org/10.1016/j.tet.2018.03.042]

Cite As

Letters in Organic Chemistry

Efficient Synthesis of the Key Intermediate of Scopolamine by [4+3] Cycloaddition Reaction

Abstract

Graphical Abstract