Chiral 1,4-Oxazino[4,3-a]indoles as a Challenging Scaffold: Syntheses and Properties

Dedicated to Professor Alain Krief on the occasion of his 80^th birthday

Abstract

In the last few decades, there has been an increasing interest in the development of new syntheses of oxazinoindoles, a tricyclic backbone bearing an indole core structure fused with a morpholine ring, in particular because these molecules have interesting bioactive properties, such as antidepressant, anti-inflammatory, or antitumor activity. There are a few reported racemic strategies for the synthesis of oxazinoindoles, but only four reports of enantioselective syntheses. This short review presents an overview of these enantioselective strategies as well as the evaluation of chiral oxazinoindoles for their bioactive properties.

1 Introduction

2 Racemic Syntheses and Evaluation of Chiral Oxazinoindoles after Separation

3 Enantioselective Catalytic Syntheses of Oxazinoindoles

4 Conclusion

Key words

oxazinoindoles - bioactive molecules - chirality - chiral separation - asymmetric syntheses

Publikationsverlauf

Eingereicht: 02. Juni 2022

Angenommen nach Revision: 11. Juli 2022

Accepted Manuscript online:
11. Juli 2022

Artikel online veröffentlicht:
03. August 2022

• References

• 1a Kochanowska-Karamyan AJ, Hamann MT. Chem. Rev. 2010; 110: 4489
• 1b Vitaku E, Smith DT, Njardarson JT. J. Med. Chem. 2014; 57: 10257
• 1c Kaushik N, Kaushik N, Attri P, Kumar N, Kim C, Verma A, Choi E. Molecules 2013; 18: 6620
• 1d Mauger A, Jarret M, Kouklovsky C, Poupon E, Evanno L, Vincent G. Nat. Prod. Rep. 2021; 38: 1852
• 1e Milcendeau P, Sabat N, Ferry A, Guinchard X. Org. Biomol. Chem. 2020; 18: 6006
• 2a Demerson CA, Santroch G, Humber LG, Charest MP. J. Med. Chem. 1975; 18: 577
• 2b Zimmerman WT. WO 9110668 A1, 1991
• 2c Farina C, Gagliardi S, Misiano P, Celestini P, Zunino F. WO 2005/105213 A3, 2005
• 3a Abbiati G, Canevari V, Caimi S, Rossi E. Tetrahedron Lett. 2005; 46: 7117
• 3b Vandavasi JK, Hu W.-P, Senadi GC, Boominathan SS. K, Chen H.-Y, Wang J.-J. Eur. J. Org. Chem. 2014; 2014: 6219
• 3c An J, Chang N.-J, Song L.-D, Jin Y.-Q, Ma Y, Chen J.-R, Xiao W.-J. Chem. Commun. 2011; 47: 1869
• 3d Pecnard S, Hamze A, Bignon J, Prost B, Deroussent A, Gallego-Yerga L, Peláez R, Paik JY, Diederich M, Alami M, Provot O. Eur. J. Med. Chem. 2021; 223: 113656
• 3e Palomba M, Vinti E, Marini F, Santi C, Bagnoli L. Tetrahedron 2016; 72: 7059
• 3f Tang C.-Y, Tao Y, Wu X.-Y, Sha F. Adv. Synth. Catal. 2014; 356: 609
• 3g Sathiyanaranan AM, Gharpure S. Chem. Commun. 2011; 47: 3625
• 3h Zheng Y, Tice CM, Singh SB. Bioorg. Med. Chem. Lett. 2014; 24: 3673
• 3i Wei L, Liu L, Zhang J. Org. Biomol. Chem. 2014; 12: 6869
• 4a Fuchibe K, Kaneko T, Mori K, Akiyama T. Angew. Chem. Int. Ed. 2009; 48: 8070
• 4b Niu S.-L, Hu J, He K, Chen Y.-C, Xiao Q. Org. Lett. 2019; 21: 4250
• 4c Gogoi A, Guin S, Rout SK, Patel BK. Org. Lett. 2013; 15: 1802
• 5a Chirucci M, Matteucci E, Cera G, Fabrizi G, Bandini M. Chem. Asian J. 2013; 8: 1776
• 5b Naoe S, Saito T, Uchiyama M, Oishi S, Fujii N, Ohno H. Org. Lett. 2015; 17: 1774
• 5c Naoe S, Yoshida Y, Oishi S, Fujii N, Ohno H. J. Org. Chem. 2016; 81: 5690
• 6 Pecnard S, Hamze A, Pozzo J.-L, Alami M, Provot O. Eur. J. Med. Chem. 2021; 224: 113728
• 7 Buzard DJ, Schrader TO, Zhu X, Lehmann J, Johnson B, Kasem M, Kim SH, Kawasaki A, Lopez L, Moody J, Han S, Gao Y, Edwards J, Barden J, Thatte J, Gatlin J, Jones RM. Bioorg. Med. Chem. Lett. 2015; 25: 659
• 8 Chen J, Tao L.-X, Xiao W, Ji S.-S, Wang J.-R, Li X.-W, Zhang H.-Y, Guo Y.-W. Bioorg. Med. Chem. Lett. 2016; 26: 3765
• 9 The neuroprotective effect of these compounds on Aβ_25–35-induced neurotoxicity in SH-SY5Y cells. The cell viability in control was taken as 100%, and the average value of cell viability under Aβ_25–35 exposure was 62.1 ± 2.2%. The positive control is epigallocatechin gallate.
• 10 Bandini M, Bottoni A, Eichholzer A, Miscione GP, Stenta M. Chem. Eur. J. 2010; 16: 12462
• 11 Biannic B, Aponick A. Eur. J. Org. Chem. 2011; 2011: 6605
• 12 Chiarucci M, Mocci R, Syntrivanis L.-D, Cera G, Mazzanti A, Bandini M. Angew. Chem. Int. Ed. 2013; 52: 10850
• 13 Lombardo VM, Thomas CD, Scheidt KA. Angew. Chem. Int. Ed. 2013; 52: 12910
• 14a Kopecky DJ, Rychnovsky DJ. J. Am. Chem. Soc. 2001; 123: 8420
• 14b Chio FK, Warne J, Gough D, Penny M, Green S, Coles SJ, Hursthouse MB, Jones P, Hassall L, McGuire TM, Dobbs AP. Tetrahedron 2011; 67: 5107
• 15 Dupeux A, Michelet V. J. Org. Chem. 2021; 86: 17738
• 16a Tomás-Mendivil E, Starck J, Ortuno J.-C, Michelet V. Org. Lett. 2015; 17: 6126
• 16b Tomás-Mendivil E, Heinrich CF, Ortuno J.-C, Starck J, Michelet V. ACS Catal. 2017; 7: 380
• 16c Mariaule G, Newsome G, Toullec PY, Belmont P, Michelet V. Org. Lett. 2014; 16: 4570
• 16d Michalska M, Grudzień K, Małecki P, Grela K. Org. Lett. 2018; 20: 954
• 16e Handa S, Slaughter LM. Angew. Chem. Int. Ed. 2012; 51: 2912