RSS-Feed abonnieren
Bitte kopieren Sie die angezeigte URL und fügen sie dann in Ihren RSS-Reader ein.
https://www.thieme-connect.de/rss/thieme/de/10.1055-s-00000084.xml
Synthesis 2022; 54(24): 5540-5550
DOI: 10.1055/s-0042-1751361
DOI: 10.1055/s-0042-1751361
paper
Protecting-Group-Free Synthesis of Novel Cannabinoid-Like 2,5-Dihydrobenzoxepines
We acknowledge the financial support from the German Federal Ministry of Education and Research in the program VIPplus for the project CannaCell (03VP06370).
Abstract
An efficient synthesis of 2,5-dihydrobenzoxepine analogues was developed without using protecting groups. Regioselective allylation was optimized through a recent method utilizing magnesium dicarboxylates. Grubbs catalysts were applied to investigate ring-closing metathesis. The scope of the present route was extended to produce four analogues, which provided novel cannabinoid-like 2,5-dihydrobenzoxepines in sufficient quantities to permit in vitro assays on recombinant CB1/CB2 receptors. In vitro assays related to CB1/CB2 receptors did not indicate any activity.
Key words
2,5-dihydrobenzoxepine - radulanin A - benzoxepin cannabinoids - regioselective allylation - ring-closing metathesisSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0042-1751361.
- Supporting Information
Publikationsverlauf
Eingereicht: 27. Juni 2022
Angenommen nach Revision: 21. Juli 2022
Artikel online veröffentlicht:
13. September 2022
© 2022. Thieme. All rights reserved
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
References
- 1a Flemming T, Muntendam R, Steup C, Kayser O. In Bioactive Heterocycles IV. Topics in Heterocyclic Chemistry, Vol. 10. Khan MT. H. Springer; Berlin: 2007
- 1b Nguyen G.-N, Kayser O. In Biosynthesis and Chemical Modifications of Minor Cannabinoids, Encyclopedia of Life Sciences. Wiley; New York: 2020
- 2a Martin BR, Mechoulam R, Razdan RK. Life Sci. 1999; 65: 573
- 2b Schwope DM, Karschner EL, Gorelick DA, Huestis MA. Clin. Chem. 2011; 57: 1406
- 2c Soethoudt M, Grether U, Fingerle J, Grim TW, Fezza F, de Petrocellis L, Ullmer C, Rothenhäusler B, Perret C, van Gils N, Finlay D, MacDonald C, Chicca A, Gens MD, Stuart J, de Vries H, Mastrangelo N, Xia L, Alachouzos G, Baggelaar MP, Martella A, Mock ED, Deng H, Heitman LH, Connor M, Di Marzo V, Gertsch J, Lichtman AH, Maccarrone M, Pacher P, Glass M, van der Stelt M. Nat. Commun. 2017; 8: 13958
- 2d Ligresti A, De Petrocellis L, Di Marzo V. Physiol. Rev. 2016; 94: 1593
- 3 Hanuš LO, Meyer SM, Muñoz E, Taglialatela-Scafati O, Appendino G. Nat. Prod. 2016; 33: 1357
- 4 Gülck T, Møller B.. Trends Plant Sci. 2020; 25: 985
- 5a Asakawa Y, Kusube E, Takemoto T, Suire C. Phytochemistry 1978; 17: 2115
- 5b Asakawa Y, Takeda R, Toyota M, Takemoto T. Phytochemistry 1981; 20: 858
- 5c Asakwa Y, Hashimoto T, Takikawa K, Tori M, Ogawa S. Phytochemistry 1991; 30: 235
- 5d Toyota M, Shimamura T, Ishii H, Renner M, Braggins J, Asakawa Y. Chem. Pharm. Bull. 2002; 50: 1390
- 5e Harinantenaina L, Takahara Y, Nishizawa T, Kohchi C, Soma G.-I, Asakawa Y. Chem. Pharm. Bull. 2006; 54: 1046
- 5f Toyota M, Omatsu I, Braggins J, Asakawa Y. Chem. Pharm. Bull. 2011; 59: 480
- 5g Wang X, Li L, Zhu R, Zhang J, Zhou J, Lou H. J. Nat. Prod. 2017; 80: 3143
- 6a Siddiqui BS, Begum S, Siddiqui S, Lichter W. Phytochemistry 1995; 39: 171
- 6b Engler M, Anke T, Sterner O, Brandt U. J. Antibiot. 1997; 50: 325
- 6c Lemaire P, Balme G, Desbordes P, Vorb J.-P. Org. Biomol. Chem. 2003; 1: 4209
- 6d Spring O, Pfannstiel J, Klaiber I, Conrad J, Beifuß U, Apel L, Aschenbrenner A.-K, Zipper R. Phytochemistry 2015; 119: 83
- 6e Malefo MS, Ramadwa TE, Famuyide IM, McGaw LJ, Eloff JN, Sonopo MS, Selepe MA. J. Nat. Prod. 2020; 83: 2508
- 6f Zhang L, Qiu P, Ding L, Li Q, Song J, Han Z, He S. Chem. Nat. Compd. 2020; 56: 109
- 7 Asakawa Y, Nagashima F, Ludwiczuk A. J. Nat. Prod. 2020; 83: 756
- 8 Magauer T, Sokol KR. Synthesis 2021; 53: 4187
- 9 Bruder M, Haseler PL, Muscarella M, Lewis W, Moody CJ. J. Org. Chem. 2010; 75: 353
- 10 Calder ED. D, Sharif SA. I, McGonagle FI, Sutherland A. J. Org. Chem. 2015; 80: 4683
- 11 Chicca A, Schafroth MA, Reynoso-Moreno I, Erni R, Petrucci V, Carreira EM, Gertsch J. Sci. Adv. 2018; 4: eaat2166
- 12 Stefinovic M, Snieckus V. J. Org. Chem. 1998; 63: 2808
- 13a Yamaguchi S, Furihata K, Miyazawa M, Yokoyama H, Hirai Y. Tetrahedron Lett. 2000; 41: 4787
- 13b Yamaguchi S, Tsuchida N, Miyazawa M, Hirai Y. J. Org. Chem. 2005; 70: 7505
- 14 Zhang W, Baudouin E, Cordier M, Frison G, Nay B. Chem. Eur. J. 2019; 25: 8643
- 15 Lockett-Walters B, Thuillier S, Baudion E, Nay B. Org. Lett. 2022; 24: 4029
- 16 Bahou KA, Braddock DC, Meyer AG, Savage GP. Org. Lett. 2017; 19: 5332
- 17 Moreno-Manas M, Pleixats R, Santamaria A. Synlett 2001; 1784
- 18 Mandal S, Banerjee J, Maity S, Chattopadhyay SK. Helv. Chim. Acta 2021; 104: e2000216
- 19 Nguyen G.-N, Jordan EN, Kayser O. J. Nat. Prod. 2022; 85: 1555
- 20 Raikar SB, Nuhant P, Delpech B, Marazano C. Eur. J. Org. Chem. 2008; 8: 1358
- 21 Glüsenkamp K.-H, Büchi G. J. Org. Chem. 1986; 51: 4481
- 22 Zhang J, Xiong W, Wen Y, Fu X, Lu X, Zhang G, Wang C. Org. Biomol. Chem. 2022; 20: 1117
- 23 Cheng-Sanchez I, Sarabia F. Synthesis 2018; 50: 3749
- 24a Fu GC, Grubbs RH. J. Am. Chem. Soc. 1992; 114: 5426
- 24b Fu GC, Grubbs RH. J. Am. Chem. Soc. 1992; 114: 7324
- 25a Fu GC, Nguyen ST, Grubbs RH. J. Am. Chem. Soc. 1993; 115: 9856
- 25b Schwab P, France MB, Ziller JW, Grubbs RH. Angew. Chem., Int. Ed. Engl. 1995; 34: 2039
- 25c Scholl M, Ding S, Lee CW, Grubbs RH. Org. Lett. 1999; 1: 953
- 26a Harrity JP. A, La DS, Cefalo DR, Visser MS, Hoveyda AH. J. Am. Chem. Soc. 1998; 120: 2343
- 26b Garber SB, Kingsbury JS, Gray BL, Hoveyda AH. J. Am. Chem. Soc. 2000; 122: 8168
- 27a Malcolmson SJ, Meek SJ, Sattely ES, Schrock RR, Hoveyda AH. Nature 2008; 456: 933
- 27b Lee Y.-L, Schrock RR, Hoveyda AH. J. Am. Chem. Soc. 2009; 131: 10652
- 27c Sattely ES, Meek SJ, Malcolmson SJ, Schrock RR, Hoveyda AH. J. Am. Chem. Soc. 2009; 131: 943
- 27d Yu M, Wang C, Kyle AF, Jakubec P, Dixon DJ, Schrock RR, Hoveyda AH. Nature 2011; 479: 88
- 27e Wang C, Haeffner F, Schrock RR, Hoveyda AH. Angew. Chem. Int. Ed. 2013; 52: 1939
- 28a Jiang AJ, Simpson JH, Müller P, Schrock RR. J. Am. Chem. Soc. 2009; 131: 7770
- 28b Rosebrugh LE, Herbert MB, Marx VM, Keitz BK, Grubbs RH. J. Am. Chem. Soc. 2013; 135: 1276
- 28c Cannon JS, Grubbs RH. Angew. Chem. Int. Ed. 2013; 52: 9001
- 29 Chicca A, Marazzi J, Gertsch J. Br. J. Pharmacol. 2012; 167: 1596
- 30 Mäder P, Bartholomäus R, Nicolussi S, Baumann A, Weis M, Chicca A, Rau M, Simão AC, Gertsch J, Altmann K.-H. ChemMedChem 2021; 16: 145
- 31 Gfeller D, Michielin O, Zoete V. Bioinformatics 2013; 29: 3073
- 32 Daina A, Michielin O, Zoete V. Nucleic Acids Res. 2019; 47: 357