Subscribe to RSS
Download PDF
DOI: 10.1055/a-2746-2191
Amine-Facilitated Tandem Aerobic Oxidation and Cyclization to Tetrahydro-β-Carbolines
Authors
We acknowledge financial support from the National Natural Science Foundation of China (22278249), the Taishan Scholars Program (tsqn202306151) and the Natural Science Foundation of Shandong Province (ZR2021YQ13)
Supported by: National Natural Science Foundation of China 22278249,tsqn202306151
Abstract
A tandem oxidation–condensation–cyclization of alcohols with tryptamines was developed under open-air atmosphere. Various harmless and readily available alcohols were used instead of aldehydes for the condensation with amines and subsequent cyclization to afford pharmacologically active tetrahydro-β-carboline products. Mechanistic studies reveal that the base promotes the initial dehydrogenation of alcohols to aldehydes, and the subsequent amine trapping of the reactive aldehydes is the key driving force that shifts the equilibrium, thus allowing the catalytic cycle to proceed continuously to full conversion. A 30 mmol-scale (6.5 g) experiment and the synthesis of two bioactive molecules demonstrated that the method is operationally simple, cost effective, and highly practical.
Keywords
Alcohols - Tryptamines - Tandem oxidation - Metal-free catalysis - Open air - Tetrahydro-β-carbolinePublication History
Received: 01 October 2025
Accepted after revision: 12 November 2025
Accepted Manuscript online:
12 November 2025
Article published online:
31 December 2025
© 2025. Thieme. All rights reserved.
Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
-
References
- 1a Chrzanowska M, Grajewska A, Rozwadowska MD. Chem Rev 2016; 116: 12369-12465
- 1b Frederich M, Tits M, Angenot L. Trans R Soc Trop Med Hyg 2008; 102: 11-19
- 1c Ndagijimana A, Wang X, Pan G, Zhang F, Feng H, Olaleye O. Fitoterapia 2013; 86: 35-47
- 1d O’Connor SE, Maresh JJ. Nat Prod Rep 2006; 23: 532-547
- 1e Singh TP, Singh OM. Mini Rev Med Chem 2018; 18: 9-25
- 2 Maity P, Adhikari D, Jana AK. Tetrahedron 2019; 75: 965-1028
- 3 Balfour JA, Buckley MMT. Drugs 1991; 42: 274-299
- 4a Daugan A, Grondin P, Ruault C. et al. J Med Chem 2003; 46: 4525-4532
- 4b Kloner RA, Mitchell M, Emmick JT. Am J Cardiol 2003; 92: 37-46
- 5a Garrett L, Carrier O, Douglas BH. Eur J Pharmacol 1967; 2: 236-238
- 5b Luxenberg JAY, Feigenbaum LZ. J Am Geriatr Soc 1983; 31: 556-559
- 6a Chiou W-H, Lin G-H, Hsu C-C, Chaterpaul SJ, Ojima I. Org Lett 2009; 11: 2659-2662
- 6b Lood CS, Koskinen AMP. Chem Heterocycl Compd 2015; 50: 1367-1387
- 6c Spindola HM, Vendramini-Costa DB, Rodrigues MT, Foglio MA, Pilli RA, Carvalho JE. Pharmacol Biochem Behav 2012; 102: 133-138
- 7 Tulyaganov TS, Nazarov OM, Levkovich MG, Abdullaev ND. Chem Nat Compd 2001; 37: 61-64
- 8a Pictet A, Spengler T. Ber Dtsch Chem Ges 1911; 44: 2030-2036
- 8b Cox ED, Cook JM. Chem Rev 1995; 95: 1797-1842
- 8c Stöckigt J, Antonchick AP, Wu F, Waldmann H. Angew Chem Int Ed 2011; 50: 8538-8564
- 8d Wagen CC, McMinn SE, Kwan EE, Jacobsen EN. Nature 2022; 610: 680-686
- 8e Zheng C, Xia Z-L, You S-L. Chem 2018; 4: 1952-1966
- 9a Glinsky-Olivier N, Yang S, Retailleau P, Gandon V, Guinchard X. Org Lett 2019; 21: 9446-9451
- 9b Karpov AS, Oeser T, Müller TJJ. Chem Commun 2004; 1502-1503
- 9c Ryabukhin SV, Panov DM, Plaskon AS, Tolmachev AA, Smaliy RV. Monatsh Chem 2012; 143: 1507-1517
- 9d Srinivasan N, Ganesan A. Chem Commun 2003; 916-917
- 9e Youn SW. J Org Chem 2006; 71: 2521-2523
- 10a Klausen RS, Jacobsen EN. Org Lett 2009; 11: 887-890
- 10b Muratore ME, Holloway CA, Pilling AW, Storer RI, Trevitt G, Dixon DJ. J Am Chem Soc 2009; 131: 10796-10797
- 10c Raheem IT, Thiara PS, Peterson EA, Jacobsen EN. J Am Chem Soc 2007; 129: 13404-13405
- 10d Seayad J, Seayad AM, List B. J Am Chem Soc 2006; 128: 1086-1087
- 10e Sewgobind NV, Wanner MJ, Ingemann S, de Gelder R, van Maarseveen JH, Hiemstra H. J Org Chem 2008; 73: 6405-6408
- 10f Taylor MS, Jacobsen EN. J Am Chem Soc 2004; 126: 10558-10559
- 10g Wanner MJ, van der Haas RNS, de Cuba KR, van Maarseveen JH, Hiemstra H. Angew Chem Int Ed 2007; 46: 7485-7487
- 11a Chan Y-C, Sak MH, Frank SA, Miller SJ. Angew Chem Int Ed 2021; 60: 24573-24581
- 11b Mittal N, Sun DX, Seidel D. Org Lett 2014; 16: 1012-1015
- 11c Nakamura S, Matsuda Y, Takehara T, Suzuki T. Org Lett 2022; 24: 1072-1076
- 11d Qi L, Hou H, Ling F, Zhong W. Org Biomol Chem 2018; 16: 566-574
- 12 Du Y, Semghouli A, Mei H, Kiss L, Han J. Adv Synth Catal 2024; 366: 3050-3084
- 13 Nalikezhathu A, Cherepakhin V, Williams TJ. Org Lett 2020; 22: 4979-4984
- 14 Yang P, Zhang C, Gao W-C. et al. Chem Commun 2019; 55: 7844-7847
- 15 Shao Z, Zhang X, Li X. et al. Chem Eur J 2023; 29: e202203758
- 16 Kobayashi M, Hikawa H, Enda T, Kikkawa S, Azumaya I. Eur J Org Chem 2025; 28: e202401269
- 17 Sravanthi TV, Manju SL. Eur J Pharm Sci 2016; 91: 1-10
- 18 Herbert RB, Mann J. J Chem Soc Perkin Trans 1982; 1: 1523.I-1525.I