Synthesis of 2-aroyl- and (2-oxo-2H-4-chro menyl) furo[3,2-g]neoflavones

Hlibov, EK
1Moskvina, VS
Shokol, TV
1Khilya, VP
1Taras Shevchenko National University of Kyiv
Dopov. Nac. akad. nauk Ukr. 2019, 11:66-72
https://doi.org/10.15407/dopovidi2019.11.066
Section: Chemistry
Language: Ukrainian
Abstract: 

This paper is devoted to the development of a practical and effective synthesis technique for 2-aroylfuro[3,2-g] chromen-7-ones and 2-(2-oxo-2H-4-chromenyl)furo[3,2-g]chromen-7-ones that are modified analogs of natural furocoumarin psoralen. The interaction of 6-acetyl-7-hydroxy-8-methylchro men-2-ones with phenacylbromides and 4-chloromethylcoumarins in dimethylformamide in the presence of K2CO3 upon heating is stu died. 2-Aroylfuro[3,2-g]chromen-7-ones were obtained in one step in good yields as a result of simultaneous alkylation of 6-acethyl-7-hydroxy-8-methylchromen-2-ones by corresponding phenacylbromides followed by condensation of carbonyl group. The use of 1-benzo[b]furan-2-yl-2-bromo-1-ethanone in this heterocyclization was completed by the formation of 2-(ben zofuran-2-carbonyl)-3,9-dimethyl-5-phenyl-7H-furo[3,2-g]chromen-7- one. As a result of the interaction of 6-ace tyl-7-hydroxy-8-methylneoflavone with 4-chloromethylcoumarins under the conditions developed by us, 2-coumarinyl-5-phenyl-7H-furo[3,2-g]chromen-7-ones with coumarin substituent in the second position were obtained in good yields. The structure of the obtained compounds was proved using the methods of NMR spect roscopy. The obtained compounds are promising both for medical chemistry and for subsequent synthetic transformations, as well as for the study of their physico-chemical properties and structural features.

Keywords: 2-g]neoflavones, 4-chloromethylcoumarins, 6-аcetyl-7-hydroxyneoflavones, furo[3, heterocyclization, phenacyl bromides
References: 

1. Lowes, M. A., Bowcock, A. M. & Krueger, J. G. (2007). Pathogenesis and therapy of psoriasis. Nature, 445, pp. 866-873. doi: https://doi.org/10.1038/nature05663
2. Komissarenko, A. N., Komissarenko, S. N., Socyperova, I. F. (1995). Coumarins of Ukrainian the genus heracleum L. plants fruits. Visnyk Farmatsii, No. 3-4, pp. 99-103 (in Ukrainian).
3. Zhang, B.-L., Fan, C.-Q., Dong, L., Wang, F.-D. & Yue, J.-M. (2010). Structural modification of a specific antimicrobial lead against Helicobacter pylori discovered from traditional Chinese medicine and a struc tu reactivity relationship study. Eur. J. Med. Chem., 45, No. 11, pp. 5258-5264. doi: https://doi.org/10.1055/s-0036-1588784
4. Oliveira, A. M. A., Raposo, M. M. M., Oliveira-Campos, A. M. F., Machado, A. E. H., Puapairoj, P., Pedro, M., Nascimento, M. S. J., Portela, C., Afonso, C. & Pinto, M. (2006). Psoralen analogues: synthesis, inhibitory activity of growth of human tumor cell lines and computational studies. Eur. J. Med. Chem., 41, No. 3, pp. 367–372. doi: https://doi.org/10.1002/adsc.201500319
5. Timonen, Ju. M., Vuolteenaho, K., Leppänen, T., Nieminen, R. M., Aulaskari, P., Jänis, J., Vainiotalo, P. & Moilanen, E. (2018). Synthesis of novel anti-inflammatory psoralen derivatives — structures with distinct anti-inflammatory activities. J. Heterocycl. Chem., 55, No. 11, pp. 2590-2597. doi: https://doi.org/10.1002/jhet.3318
6. Pat. WO2016/146583 A1. IPC C07D 493/04, C07D 495/04, C07D 498/04, A61K 31/352, A61K 31/381, A61K 31/424, A61P 25/00, A61P 29/00. Kvl.3 inhibitors and their medical application. Tasler, S., Krimmelbein, I., Kraus, J. & Zaja, M. Publ. 14.03.2016.
7. Shah, K. R. & Trivedi, K. N. (1974). Studies in the synthesis of furocoumarins. XXIII Synthesis of substituted psoralens from 2-bromoresorcinol. Aust. J. Chem., 27, pp. 1971-1976. doi: https://doi.org/10.1071/CH9741971
8. Ahluwalia, V. K., Aggarwal, R. & Bala, S. (1986). Dehydrogenation of dihydrofuranocoumarins to furanocoumarins using 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). Indian J. Chem. B, 25. No. 12, pp. 1252.
9. Ahluwalia V.K., Khanduri C.H. (1989). Synthesis of 6-aryl-5-phenyl-7H-furo(3,2-g)(1)benzopyran-7-ones and 8-aryl-7-phenyl-9H-benzofuro(3,2-g)(1)benzopyran-9-ones under phase transfer catalysis conditions. Indian J. Chem. B, 28, No. 1-11, pp. 599-601. doi: https://doi.org/10.1002/chin.198944210
10. Kitamura, T. & Otsubo, K. (2012). Palladium-catalyzed intramolecular hydroarylation of 6-benzofuranyl alkynoates. Heterocycles, 86, No. 1, pp. 759-766. doi: https://doi.org/10.3987/COM-12-S(N)36
11. Ahluwalia, V. K., Prakash, Ch. & Bala, S. (1980). A convenient synthesis of psoralen derivatives: psoralen, 4-methyl-psoralen and 4-phenyl-psoralen. Monatsh. Chem., 111, pp. 877-882. doi: https://doi.org/10.1007/BF00899252
12. Desai, S. M. & Trivedi, K. N. (1985). Studies in the synthesis of furocoumarins: Part XXVII — Synthesis of 5′-methyl-3,4-diphenylpsoralene and angelicin. Indian J. Chem. B, 24, No. 1, pp. 47-50. doi: https://doi.org/10.1002/chin.198522203
13. Garazd, M. M., Garazd, Ya. L., Shilin, S. V. & Khilya, V. P. (2000). Modified coumarins. I. Synthesis of 5-phenyl-7H-furo[2,3-g]chromen-7-ones and 9-phenyl-7H-furo-[2,3-f]chromen-7-ones. Chem. Nat. Comp., 36, No. 5, pp. 478-484. doi: https://doi.org/10.1023/A:1002883305908
14. Garazd, M. M., Garazd, Ya. L., Ogorodniichuk, A. S., Khilya, V. P. (2002). Modified coumarins. 8. Synthesis of substituted 5-(4-methoxyphenyl)-7H-furo[3,2-g]chromen-7-ones. Chem. Nat. Comp., 38, No. 6, pp. 539-548. doi: https://doi.org/10.1023/A:1022626402415
15. Moskvina, V. S. & Khilya, V. P. (2008). Synshesis of pyrano[2,3-f]chromen-2,8-diones and pyrano[3,2-g]- chromen-2,8-diones based on o-hydroxyformyl(acyl)neoflavonoids. Chem. Nat. Comp., 44, No. 1, pp. 16-23. doi: https://doi.org/10.1007/s10600-008-0006-z