3-acyl-1H-isochromen-1-one, ethane-1,2-diamine, recyclization, pyrazino[1,2-b]isoquinolin-6-one, reduction


A straightforward approach to synthesizing the pyrazino[1,2-b]isoquinolin-6-one, which serves as the basis for several biologically active compounds of natural origin, is proposed. In a single step, the interaction of 3-formyl- and 3-acyl-1H-isochromen-1-ones with ethane-1,2-diamine in an aqueous or aqueous alcohol medium leads to the formation of the 3,4-dihydro-6H-pyrazino[1,2-b]isoquinolin-6-one ring. Using the derivative with a methyl group at position 1, it was demonstrated that this heterocyclic system can be reduced to both 1-methyl-1,2,3,4- tetrahydro-6H-pyrazino[1,2-b]isoquinolin-6-one (through the action of sodium triacetoxyboride) and to 1-methyl-1,3,4,6,11,11a-hexahydro-2H-pyrazino[1,2-b]isoquinoline (through prolonged heating with an excess of lithium aluminium hydride). A novel method for obtaining 3-formyl-1H-isochromen-1-one (also known as the natural compound Artemidinal) is presented. The proposed techniques employ simple synthetic procedures and inexpensive reagents.


Download data is not yet available.


Suthiphasilp, V., Maneerat, W., Rujanapun, N., Duangyod, T., Charoensup, R., Deachathai, S., Andersen, R. J., Patrick, B. O., Pyne, S. G. & Laphookhieo, S. (2020). α-Glucosidase inhibitory and nitric oxide production inhibitory activities of alkaloids isolated from a twig extract of Polyalthia cinnamomea. Bioorg. Med. Chem., 28, Iss. 10, 115462. https://doi.org/10.1016/j.bmc.2020.115462

Tao, S., Wang, Y., Hong, R. & Huang, S.-H. (2022). Potent antibiotic lemonomycin: a glimpse of its discovery, origin, and chemical synthesis. Molecules, 27, Iss. 13, 4324. https://doi.org/10.3390/molecules27134324

Sullivan, H. B. & Day, A. R. (1964). Synthesis of 1,3,4,6,11,1a-hexahydro-2H-pyrazino[l,2-b]isoquinoline and perhydro-1H-pyrazino[1,2-а]quinoline. J. Org. Chem., 29, Iss. 2, pp. 326-328. https://doi.org/10.1021/ jo01025a018

Kato, H., Koshinaka, E., Arata, Y. & Hanaoka, M. (1973). Studies on 1-azabicyclo compounds. XV. Oxidation of 1,3,4,6,11,11a-hexahydro-2H-pyrazino[1,2-b]isoquinolin-1-one derivatives with mercuric acetate, and their conversion into 1,2,3,4,5,6,7,8-octahydro-2-methyl-2,5-benzodiazecine and related compounds. Chem. Pharm. Bull., 21, Iss. 9, pp. 2039-2047. https://doi.org/10.1248/cpb.21.2039

Couturier, C., Schlama, T. & Zhu, J. (2006). Synthetic studies towards (–)-lemonomycin, synthesis of fused tetracycles. Synlett, 2006, Iss. 11, pp. 1691-1694. https://doi.org/10.1055/s-2006-944225

Huck, L., González, J. F., de la Cuesta, E., Menéndez, J. C. & Avendaño, C. (2011). 1,3-Dipolar cycloadditions from tricyclic hemiaminals. Synthesis of the quinocarcin core through catalyst-free generation of azomethine ylides. Org. Biomol. Chem., 9, Iss. 18, pp. 6271-6277. https://doi.org/10.1039/c1ob05181d

Sarnpitak, P. & Krasavin, M. (2014). Convenient access to novel functionalized pyrazino[1,2-b]isoquinolin-6- one and diazepino[1,2-b]isoquinolin-7-one scaffolds via the Cushman multicomponent reaction followed by post-condensation. Tetrahedron Lett., 55, Iss. 14, pp. 2299-2303. https://doi.org/10.1016/j.tetlet.2014.02.099

Konovalenko, А., Shablykina, O., Ishchenko, V. & Khilya, V. (2017). New 3-hetarylisocoumarins. Visnyk Kyyivs’koho natsional’noho universytetu imeni Tarasa Shevchenka. Khimiya, Iss. 1, pp. 6-8 (in Ukrainian).

Gianni, J., Pirovano, V. & Abbiati, G. (2018). Silver triflate/p-TSA co-catalysed synthesis of 3-substituted isocoumarins from 2-alkynylbenzoates. Org. Biomol. Chem., 16, pp. 3213-3219. https://doi.org/10.1039/ C8OB00436F

Syper, L. & Młochowski, J. (1984). A convenient oxidation of halomethylarenes and alcohols to aldehydes with dimethyl selenoxide and potassium benzeneselenite. Synthesis, 1984, Iss. 9, pp. 747-752. https://doi. org/10.1055/s-1984-30956

Modi, A. R., Nadkarni, D. R. & Usgaonkar, R. N. (1980). Isocoumarins. Part XVIII. Isoquinolones. Part III. 3-Formylisocoumarins, 3-formylisoquinolones, 3-(isocoumarin-3ʹ-yl)- and 3-(isoquinolon-3ʹ-yl)-acrylic acids and related compounds. Chem. Inform., 11, Iss. 39, pp. 85-86. https://doi.org/10.1002/chin.198039188



How to Cite

Konovalenko , A., Shablykin, O., Shablykina, O., Brovarets , V., & Khilya , V. (2023). A SIMPLE APPROACH TO THE 1,3,4,6,11,11а-HEXAHYDRO-2H-PYRAZINO[1,2-b]ISOQUINOLINE SYSTEM. Reports of the National Academy of Sciences of Ukraine, (4), 43–51. https://doi.org/10.15407/dopovidi2023.04.043