C2-symmetric hydroxylated biphenyls have attracted considerable interest because of the biological activity exerted by a number of natural occurring compounds containing this moiety and because of their ability to transmit conformational information in stoichiometric and catalytic processes [a]. The geometrical possibilities offered by chemical transformation of the biphenyl skeleton make it a versatile building block in drug synthesis and catalysis [b].With the aim to synthetized new biphenyl compounds, we have considered chalcons, an important class of bioactive compounds that has attracted much interest not only from the synthetic and biosynthetic perspectives but also due to its broad interesting biological activities [c]. Chalcone is chemically 1,3-diaryl-2-propen-1-one in which the two aromatic rings are bonded by a three-carbon ?,?-unsaturated carbonyl system [d]. Our study was aimed to prepare new chalcones compounds starting from commercial 1,1'-biphenyl-4,4'-diol, an exametabolite producted from cyanobacteria. For this purpose we prepared 4,4'-dihydroxy-[1,1'-biphenyl]-3,3'-dicarbaldehyde (bis salicylaldehyde) via formylation reaction of 1,1'- biphenyl-4,4'-diol with hexamethylenetetramine in the presence of trifluoroacetic acid [e]. Claisen-Schmidt condensation of bis salicylaldeide with variously substituted acetophenones under microwaves technology provided the desired chalcons derivatives in good yields. Another class of compounds we have considered was a curcumin related biphenyls. In a previous study, we prepared dimer of OMe-dehydrozingerone D6 [f]. We found that compound D6 was more active in inhibiting malignant melanoma and neuroblastoma cells growth when compared to curcumin itself [g]. Starting from bis salicyladehyde via Claisen-Schmidt condensation in the presence of LiOH and acetone we obtained an ?,?-unsatured keton analogue of D6. All synthesized compounds were obtained as air stable solids and easily purified by flash chromatography. Biological activity of all synthetized compounds is under evaluation. References a) K. C. Nicolaou et al., Angew. Chem. Int. Ed. 1999, 38, 2096-2152. b) G. Bringmann et al., Chem. Rev. 2011, 111, 563-639. c) D. I. Batovska et al., Pharmacology 2010, 5, 1-29. d) C. Zhuang et al., Chem. Rev. 2017, in press. e) B. Karami et al., Helv. Chim. Acta 2012, 95, 455-460. f) M. Pisano et al., Mol. Cancer 2010, 9:137. g) M. Pisano et al., BMC Cancer 2016, 16:137.
NATURAL-LIKE BIPHENILIC CHALCONES OBTAINED BY SUSTAINABLE METHODS
Maria Antonietta Dettori;Davide Fabbri;
2017
Abstract
C2-symmetric hydroxylated biphenyls have attracted considerable interest because of the biological activity exerted by a number of natural occurring compounds containing this moiety and because of their ability to transmit conformational information in stoichiometric and catalytic processes [a]. The geometrical possibilities offered by chemical transformation of the biphenyl skeleton make it a versatile building block in drug synthesis and catalysis [b].With the aim to synthetized new biphenyl compounds, we have considered chalcons, an important class of bioactive compounds that has attracted much interest not only from the synthetic and biosynthetic perspectives but also due to its broad interesting biological activities [c]. Chalcone is chemically 1,3-diaryl-2-propen-1-one in which the two aromatic rings are bonded by a three-carbon ?,?-unsaturated carbonyl system [d]. Our study was aimed to prepare new chalcones compounds starting from commercial 1,1'-biphenyl-4,4'-diol, an exametabolite producted from cyanobacteria. For this purpose we prepared 4,4'-dihydroxy-[1,1'-biphenyl]-3,3'-dicarbaldehyde (bis salicylaldehyde) via formylation reaction of 1,1'- biphenyl-4,4'-diol with hexamethylenetetramine in the presence of trifluoroacetic acid [e]. Claisen-Schmidt condensation of bis salicylaldeide with variously substituted acetophenones under microwaves technology provided the desired chalcons derivatives in good yields. Another class of compounds we have considered was a curcumin related biphenyls. In a previous study, we prepared dimer of OMe-dehydrozingerone D6 [f]. We found that compound D6 was more active in inhibiting malignant melanoma and neuroblastoma cells growth when compared to curcumin itself [g]. Starting from bis salicyladehyde via Claisen-Schmidt condensation in the presence of LiOH and acetone we obtained an ?,?-unsatured keton analogue of D6. All synthesized compounds were obtained as air stable solids and easily purified by flash chromatography. Biological activity of all synthetized compounds is under evaluation. References a) K. C. Nicolaou et al., Angew. Chem. Int. Ed. 1999, 38, 2096-2152. b) G. Bringmann et al., Chem. Rev. 2011, 111, 563-639. c) D. I. Batovska et al., Pharmacology 2010, 5, 1-29. d) C. Zhuang et al., Chem. Rev. 2017, in press. e) B. Karami et al., Helv. Chim. Acta 2012, 95, 455-460. f) M. Pisano et al., Mol. Cancer 2010, 9:137. g) M. Pisano et al., BMC Cancer 2016, 16:137.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
