SYNTHESIS OF NOVEL CHROMENE BASED HYBRID NATURAL PRODUCTS and ITS BIOLOGICAL STUDIES

Abstract

2H-Chromene or benzopyran derivatives are important motifs, which occur widely in natural products and exhibit significant biological activities such as antiviral, antitumor, antimicrobial, antidiabetic, anticoagulant, anticancer, analgesic, anti-inflammatory and antibacterial.Among the 2H-chromene derivatives, 3-cyano-2H-chromenes, 2H-chromene-3-carbaldehydes, 2-phenyl-2Hchromene-3-carbaldehydes and 3-nitro-2-phenyl-2H-chromenes are not only the core units in a number of natural products but also served as priviledged precursors for a variety of bioactive molecules and useful building blocks for natural and synthetic products. Some representative molecules of these structural motifs are presented in figure 1. newlineO newlineO newlineR newlineR=Cl,Br,OMe,OEt,OH newlineO newlineN newlineR1 newlineR2 newline1 newlineO newlineO newlineN newlineO newlineN H O 2 newline5-HT1A receptor agonist newline5-hydroxytryptamine (5-HT) receptor antagonists newline5 newlineO newline(E)-3-(6-methoxy-2H-chromen-3-yl)-1phenylprop-2-en-1-one(Antileishmanial) R = H, 2-Cl,3-Cl,4-Cl, 2,4-Cl2 3 newline(E)-4-(2-phenyl-2H-chromen-3-yl) but-3-en-2-one (antimicrobial) newlineO newlineNO2 newlineOEt newlineR newlineS14161 R=F (S14161) R=H,CN, OMe 6 (anticancer) newlineO newlineY newlineN newlineO newlineX newline(Z)-[(2H-chromen-3-yl)methylene] azolidinones(anticancer) newlineR3 newlineR2 newlineR1 newlineX =O,S;Y =S,NH,NMe R1 = H, Br,OMe; R2 = H, Me R3 = H, Me,Et,CH2CO2H 4 newlineO newlineH3CO newlineR newlineFigure 1. Chromene nitrile, chromene aldehyde and nitrochromene based biologically active molecules Nitrile, nitro and aldehyde derivatives are the versatile synthetic intermediates in organic synthesis owing to the various possible transformations of these groups into other useful phamacophores. newline iii newlineSeveral methods are known to be suitable for the synthesis of 3-cyano-2H-chromenes, 2Hchromene-3-carbaldehydes and 3-nitro-2H-chromenes; among them, the cascade reaction of salicylaldehydes with unsaturated cyano/ aldehyde/ nitro compounds are probably the most widely used approach. The corresponding products are formed according to an oxaMichael/Henry/dehydration sequence or Morita-Baylis-Hillman reaction, with of tentedious workup requirements. Many of these procedures are catalyzed by a variety