3-Hetarylisocoumarins in the synthesis of 1-functionalized 3-hetarylisoquinolines
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3-Hetarylisocoumarins in the synthesis of 1-functionalized 3-hetarylisoquinolines Artem S. Konovalenko1, Oleh V. Shablykin1, Volodymyr S. Brovarets1, Olga V. Shablykina1,2, Viktoriia S. Moskvina1,2*, Andriy V. Kozytskiy3 1
V. P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine, 1 Murmanska St., Kyiv 02094, Ukraine; e-mail: [email protected] 2 Taras Shevchenko National University of Kyiv, 60 Volodymyrska St., Kyiv 01033, Ukraine; e-mail: [email protected] 3 L. V. Pisarzhevskii Institute of Physical Chemistry, National Academy of Sciences of Ukraine, 31 Nauky Ave., Kyiv 03028, Ukraine; e-mail: [email protected] Published in Khimiya Geterotsiklicheskikh Soedinenii, 2020, 56(8), 1021–1029
Submitted February 29, 2020 Accepted after revision April 17, 2020
A convenient method was developed for the synthesis of novel isoquinolin-1(2H)-ones, 1-chloroisoquinolines, and 1-aminoisoquinolines with a heterocyclic substituent in position 3 via a recyclization of 3-hetarylisocoumarins with (NH4)2CO3. 1-Aminoisoquinolines were efficiently obtained from corresponding 1-chloro-3-hetarylisoquinolines (obtained by interaction of isoquinolin-1(2H)-ones with POCl3) and cyclic secondary amines (morpholine or 1-methylpiperazine). Literature data and preliminary results of biological assays allow to consider 1-amino-3-hetarylisoquinolines a promising family of anticancer compounds. Keywords: isocoumarin, isoquinoline, isoquinolin-1(2H)-ones, nitrogen-containing heterocycles, anticancer activity, recyclization.
Nitrogen-containing heterocycles are key components of many bioactive natural products and potent drugs (Fig. 1),1 and for this reason they are assigned as privileged motifs in drug development.2 The diverse functions of nitrogencontaining compounds highly depend on their characteristic structures, so the elaboration of N-heterocycles and the latestage modification of drug candidates with N-heterocycles have emerged as an important strategy in organic synthetic chemistry and drug discovery.3 The importance of nitrogencontaining heterocycles in medicinal chemistry has motivated many research groups to develop new and efficient protocols for their synthesis. Isoquinolones are an important family of N-heterocycles, found in naturally occurring and synthetic small molecules displaying diverse biological activities. Recently more data has emerged about isoquinolines with aromatic or heteroaromatic substituents in position 3 which have realworld applications and have been of interest to us. For instance, alkaloid of Hypecoum erectum corydamine 1 0009-3122/20/56(8)-1021©2020 Springer Science+Business Media, LLC
exhibited antimicrobial activity,4 while compound 2 extracted from seaweed Streptomyces sp.5 and compounds with general formula 36 (Fig. 1) exhibits anticancer activity. The latter compounds contain an interesting combination of a heterocyclic substituent in position 3 and an amino group in position 1.
Figure 1. Compounds containing the isoquinoline motif.
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