Synthesis of Bioactives Coumarin Derivatives, Phthalocyanines and Terminal Conjugated Dienes via a Ruthenium Catalyzed Cross-Metathesis: Application to Renewable Resources

Abstract

This study aimed for the synthesis of 4-Aryl-2-amino-6-(4-hydroxy coumarin-3-yl) pyridine-3-carbonitriles derivatives 4, suitable for use as antibacterial, anti-oxidant and anti-inflammatory activities via a versatile, readily accessible 3-((2E)-3(aryl)prop-2-enoyl)-2H-chromen-2-one, 3, which was prepared by refluxing 3-acetyl-4-hydroxycoumarin with aromatic aldehydes in chloroform in the presence of a catalytic amount of piperidine. Then the direct reaction of the obtained chalcones 3 with malonitrile in the presence of ammonium acetate in one step gave products 4. Most of the new compound 4 exhibit moderate antibacterial activity against Gram Negative bacterial strains (E. coli, K. pneumonia, S. typhi and S. flexneri). In addition, the compounds 4 were investigated for anti-oxidant activities by super oxide radical, DPPH (2,2-Diphenyl-1-picrylhydrazyl), and hydroxyl radical scavenging assays, where most of the compounds displayed significant antioxidant activities. Furthermore, these 4-Aryl-2-amino-6-(4-hydroxy coumarin-3-yl) pyridine-3-carbonitriles 4 were evaluated for anti-inflammatory activity by indirect haemolytic and lipoxygenase inhibition assays where compounds revealed good activity. The preparation of novel metal-free phthalocyanines and metallophthalocyanine complexes 11 and 12 (MPcs, M = Co, Zn, Cu and Mn), with four peripheral 6-hydroxy-4-methylcoumarin and 6-hydroxycoumarin substituents, were also prepared by cyclotetramerization of compounds 7 and 10 with the corresponding metal salts (Zn(OAc)2.2H2O, Co(OAc)2.4H2O, CuCl, Mn(OAc)2.4H2O) as a template for macrocycle formation in 2-(N,N-dimethylamino)ethanol.The electronic spectra of these compounds exhibit a band of coumarin identity together with characteristic bands of the phthalocyanine core. The new compounds were screened for antibacterial activity. Most of them are active against E. coli and S. aureus. In addition, some novel 3-acetylcoumarin derivatives 17 were prepared in good yields. Their invitro antioxidant activities were assayed by the quantitative 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity method. In this way, novel coumarin phtalonitriles derivatives 42-44 were synthesized.The synthesis of these coumarin phtalonitriles was resulting from a nucleophilic aromatic substitution reaction between 4-nitrophtalonitrile and coumarins derivatives. The complexing properties of the coumarin derivatives toward alkali metal, alkaline earth metal, some transition metals and some heavy metal cations have been investigated in acetonitrile by means of UV spectrophotometry absorption and conductivity methods. Thus, the stoichiometry of the complexes formed and their stability constants were determined. We report also in this book chapter a sequence of two ruthenium-catalyzed transformations, namely olefin cross metathesis with allylic chloride followed by elimination, which gives a straightforward access to terminal 1,3-dienes from natural products. The structures of all the new obtained compounds were confirmed by elemental analysis, IR, and multinuclear/multidimensional NMR spectroscopy (1H, 13C-NMR, NOESY, HMBC) which allowed assignment of the complete network of proton and carbon atoms).