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4 H-Chromene and 1,4-naphthoquinone systems are generally considered to be medicinally privileged scaffolds. We have designed novel conjugates that incorporated both these scaffolds, as such conjugates exhibit unique biological properties reflecting those due to individual units and collective presence. In this work, we have achieved facile, efficient, and high yielding synthesis of 19 such conjugates from readily available 2-alkylamino-4-methylsulfanyl-3-nitro-4 H-chromenes and 2-hydroxynaphthalene-1,4-dione. Highly polar nitroketene- O, N-acetal unit present in the conjugates is designed to prevent crossing blood brain barrier. We have conducted structure activity relationship (SAR) studies based on initial antimicrobial screening of a set of ten conjugates against three Gram positive bacteria [ Bacillus Subtilis, Staphylococcus aureus (MSSA), Staphylococcus aureus (MRSA)], one Gram negative bacteria ( Escherichia coli), and two fungi ( Aspergillus niger, Candida albicans). The SAR studies revealed that the conjugates with halogens at C(6) and C(8) positions of the 4 H-chromene ring having C(2)NMe group display impressive activity, almost equal to that of standard drugs. None of the conjugates, however, showed antimalarial activity, although they possess 2-hydroxy-1,4-naphthoquinone unit. [ABSTRACT FROM AUTHOR]

An efficient method was developed for the diastereoselective synthesis of novel fused dihydro-1H-furo[2,3-c]pyrazole by a one-pot, four-component reaction ofβ-keto ester, hydrazine, aromatic aldehyde, and pyridinium ylide in the presence of triethylamine under microwave irradiation in solvent-free conditions in good yields. The merits of this cascade Knoevenagel condensation/Michael addition/cyclization sequence include its high atom economy, good yields, and efficiency of producing three new bonds (two C–C and one C–O) and two stereocenters in a single operation. [ABSTRACT FROM PUBLISHER]

The reaction of N-methyl-4-(methylthio)-3-nitro-4 H-chromen-2-amine and its derivatives with 4-hydroxy-6-methyl-2 H-pyran-2-one in EtOH reflux for 5 min furnish 4-hydroxy-6-methyl-3-(2-(methylamino)-3-nitro-4 H-chromen-4-yl)-2 H-pyran-2-ones in quantitative yield. By extending EtOH reflux for 2 h, the 4 H-chromene 4-hydroxy-2-pyranone conjugates get converted into acetoacetyl coumarins. Similar reaction of N-methyl-4-(methylthio)-3-nitro-4 H-chromen-2-amine and its derivatives with 4-hydroxycoumarin in EtOH reflux furnish 4-hydroxy-2′-(methylamino)-3′-nitro-2 H,4′ H-3,4′-bichromen-2-ones. In contrast to earlier system, prolonging reflux in EtOH or in n-PrOH reflux the product gets transformed into trans-ethyl 3-(2-hydroxyaryl)-4-oxo-3,4-dihydro-2 H-furo[3,2-c]chromene-2-carboxylates. Thus, facile synthesis and characterization of 4 H-chromene 4-hydroxy-2-pyrone, 4 H-chromene 4-hydroxycoumarin conjugates, acetoacetyl coumarins and trans2,3-disubstituted dihydrofuro[3,2- c]coumarins is described. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]