Subscribe to RSS
DOI: 10.1055/a-1509-6078
Base-Free Catalytic Wittig-/Cross-Coupling Reaction Sequence as Short Synthetic Strategy for the Preparation of Highly Functionalized Arylbenzoxepinones
This work was supported by the European Regional Development Fund (ERDF, project no. 1.1.1.2/VIAA/1/16/235).
Abstract
The facile synthesis of highly functionalized building blocks with potential biological activity is of great interest to medicinal chemistry. The benzoxepinone core structures commonly exhibit biological activity. Thus, a short and efficient synthetic route towards benzoxepine containing scaffold, which enables late stage modification was developed. Namely, base-free catalytic Wittig reactions enabled the synthesis of bromobenzoxepinones from readily available starting materials. Subsequent, Suzuki–Miyaura and Stille reactions proved to be suitable methods to access a variety of benzoxepinone diaryl derivatives by late stage modification in only three steps. This three-step reaction sequence is suitable for high throughput applications and gives facile access to highly complex molecular structures, which are suitable for further functionalization. The antiproliferative properties of selected arylbenzoxepinones were tested in vitro on monolayer tumor cell line A549. Notably, in this initial screening, these compounds were found to be active in the micromolar range.
Key words
benzoxepinone - catalytic Wittig reaction - Stille reaction - Suzuki–Miyaura reaction - A549 - cytotoxicitySupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-1509-6078.
- Supporting Information
Publication History
Received: 05 April 2021
Accepted after revision: 17 May 2021
Accepted Manuscript online:
17 May 2021
Article published online:
21 June 2021
© 2021. Thieme. All rights reserved
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
References
- 1 Ishikawa NK, Yamaji K, Tahara S, Fukushi Y, Takahashi K. Phytochemistry 2000; 54: 777
- 2 Bruder M, Haseler PL, Muscarella M, Lewis W, Moody CJ. J. Org. Chem. 2010; 75: 353
- 3 Kim S, Su B.-N, Riswan S, Kardono LB. S, Afriastini JJ, Gallucci JC, Chai H, Farnsworth NR, Cordell GA, Swanson SM, Kinghorn AD. Tetrahedron Lett. 2005; 46: 9021
- 4 Vyvyan JR, Looper RE. Tetrahedron Lett. 2000; 41: 1151
- 5 Wijnberg JB. P. A, van Veldhuizen A, Swarts HJ, Frankland JC, Field JA. Tetrahedron Lett. 1999; 40: 5767
- 6 Macias FA, Molinillo JM. G, Varela RM, Torres A, Fronczek FR. J. Org. Chem. 1994; 59: 8261
- 7 Engler M, Timm A, Sterner O. J. Antibiot. 1997; 50: 330
- 8 Kuntala N, Telu JR, Anireddy JS, Pal S. Lett. Drug Des. Discov. 2017; 14: 1086
- 9 Heffron TP, Wei B, Olivero A, Staben ST, Tsui V, Do S, Dotson J, Folkes AJ, Goldsmith P, Goldsmith R, Gunzner J, Lesnick J, Lewis C, Mathieu S, Nonomiya J, Shuttleworth S, Sutherlin DP, Wan NC, Wang S, Wiesmann C, Zhu BY. J. Med. Chem. 2011; 54: 7815
- 10 Ansari MI, Hussain MK, Arun A, Chakravarti B, Konwar R, Hajela K. Eur. J. Org. Chem. 2015; 99: 113
- 11 Kuntala N, Telu JR, Banothu V, Nallapati SB, Anireddy J, Pal S. Med. Chem. Commun. 2015; 6: 1612
- 12 Saidachary G, Veera Prasad K, Divja D, Singh A, Ramesh U, Sridhar B, China Raju B. Eur. J. Med. Chem. 2014; 76: 460
- 13 Rasolofonjatovo E, Provot O, Hamze A, Rodrigo J, Bignon J, Wdzieczak-Bakala J, Lenoir C, Desravines D, Dubois J, Brion J.-D, Alami M. Eur. J. Med. Chem. 2013; 62: 28
- 14 Grandane A, Nocentini A, Werner T, Zalubovskis R, Supuran CT. Bioorg. Med. Chem. 2020; 28: 115496
- 15 Seto M, Aramaki Y, Imoto H, Aikawa K, Oda T, Kanzaki N, Iizawa Y, Baba M, Shiraishi M. Chem. Pharm. Bull. 2004; 52: 818
- 16 Gawad NM. A, Hassan GS, Georgey HH, Zorba HY. E. Med. Chem. Res. 2012; 21: 747
- 17 Tandon VK, Rai S. Lett. Drug Des. Discov. 2005; 2: 36
- 18 Iwasaki N, Ohashi T, Musoh K, Nishino H, Kado N, Yasuda S, Kato H, Ito Y. J. Med. Chem. 1995; 38: 496
- 19 Kurokawa M, Uno H, Nakamura H, Sato F, Naruto S. J. Med. Chem. 1990; 33: 504
- 20 Rigby JH, Aasuml M. Tetrahedron Lett. 2003; 44: 5029
- 21 Murakami M, Tsuruta T, Ito Y. Angew. Chem. Int. Ed. 2000; 39: 2484
- 22 Xue X, Gu Z. Org Lett. 2019; 21: 3942
- 23 Nishikata T, Nakamura K, Inoue Y, Ishikawa S. Chem. Commun. 2015; 51: 10154
- 24 Zhang C, Li T, Rao Y. Org. Chem. Front. 2017; 4: 386
- 25 Ahn S.-H, Lim HN, Lee K.-J. J. Heterocycl. Chem. 2008; 45: 1701
- 26 Grandane A, Longwitz L, Roolf C, Spannenberg A, Murua Escobar H, Junghanss C, Suna E, Werner T. J. Org. Chem. 2019; 84: 1320
- 27 Schirmer M.-L, Adomeit S, Spannenberg A, Werner T. Chem. Eur. J. 2016; 22: 2458
- 28a Suzuki A, Miyaura N. Chem. Rev. 1995; 95: 2457
- 28b Partyka DV. Chem. Rev. 2011; 111: 1529
- 28c Hooshmand SE, Heidari B, Sedghi R, Varma RS. Green Chem. 2019; 21: 381
- 29 Wang X.-Z, Deng M.-Z. J. Chem. Soc., Perkin Trans. 1 1996; 2663
- 30 Stille JK. Angew. Chem., Int. Ed. Engl. 1986; 25: 508
- 31a Chhabra N, Aseri ML, Padmanabhan D. Int. J. Appl. Basic Med. Res. 2013; 3: 16
- 31b McConathy J, Owens MJ. Prim. Care Companion J. Clin. Psychiatry 2003; 5: 70
- 32a Le Grognec E, Chretien J.-M, Zammattio F, Quintard J.-P. Chem. Rev. 2015; 115: 10207
- 32b Ayanda OS, Alafara BA, Oladele OG. Chem. Spec. Bioavailab. 2012; 24: 216
- 33 Siegel RL, Miller KD, Jemal A. CA Cancer J. Clin. 2019; 69: 7
- 34 Zhang H, Feng Q.-Q, Gong J.-H, Ma J.-P. Mol. Med. Rep. 2018; 18: 407
- 35 Giard D J, Aaronson SA, Todaro GJ, Arnstein P, Kersey JH, Dosik H, Parks WP. J. Natl. Cancer Inst. 1973; 51: 1417
- 36 Foster KA, Oster CG, Mayer MM, Avery ML, Audus KL. Exp. Cell. Res. 1998; 243: 359
- 37 Krohn K, Franke C, Jones PG, Aust H.-J, Draeger S, Schulz B. Liebigs Ann. Chem. 1992; 789
- 38 Furuya T, Strom AE, Ritter T. J. Am. Chem. Soc. 2009; 131: 1662
- 39 Yue H, Zhu C, Rueping M. Org. Lett. 2018; 20: 385
- 40 Dughera S. Synthesis 2006; 1117
- 41 Lian C, Yue G, Zhang H, Wei L, Liu D, Liu S, Fang H, Qiu D. Tetrahedron Lett. 2018; 59: 4019