Synthesis and Cytotoxicity of Coumarin Derivatives and Nordentatin

Abstract

Nordentatin and 10 coumarin derivatives were synthesized and evaluated for cytotoxicity. Compounds 6, 7, 9 and 13 showed cytotoxicity against the NCI-H187 cell line with IC50 value ranging of 3-7 µg/mL. Among synthesized coumarins, compounds 4 and 13 demonstrated cytotoxicity against the KB cell line with IC50 values of 3.94 and 6.44 µg/mL, respectively. Fortunately, coumarins 4 and 7 may be one of the new lead compounds for the development of anticancer agents due to reason that they showed weak and inactive against normal cells.

One‐pot Synthesis of Fused Dipyranocoumarins from Dihydroxycoumarins and Propargyl Chlorides under Microwave Irradiation

“…Treatment of 5,7‐dihydroxycoumarin ( 1a ) with propargyl chloride ( 2a ) in the presence of K 2 CO 3 and KI in acetone (method A) under reflux for 24 h, conditions usually applied for the propargylation of phenols [15c, 24], resulted to 5,7‐dipropargyloxycoumarin ( 3a ) in 75% yield (Table , entry 1). The same reaction under MW irradiation for 2 h led to 3a in a little better yield (Table , entry 2).…”

“…Dipyranocoumarins and almost exclusively dipetalolactone have been synthesized from 5,7‐dihydroxycoumarin and 3‐methylbut‐2‐enal [3e, 15a] in low yields or 4,4‐dimethoxy‐2‐methylbutan‐2‐ol[4, 15b] in moderate yields by refluxing in pyridine. Dipetalolactone has been obtained also by the pyrolysis in N , N ‐diethylaniline at 180°C of bis(1,1‐dimethylpropargyl) ether, derived from the reaction of 5,7‐dihydroxycoumarin and 2‐chloro‐2‐methylbut‐3‐yne [15c]. Very recently [15d], one‐pot Claisen rearrangement/Wittig reaction of 5‐formyl‐6‐hydroxy‐8‐propargyloxy‐2 H ‐chromene with carbethoxymethylenetriphenylphosphorane under MW irradiation led to dipetalolactone.…”

“…Dipetalolactone has been obtained also by the pyrolysis in N , N ‐diethylaniline at 180°C of bis(1,1‐dimethylpropargyl) ether, derived from the reaction of 5,7‐dihydroxycoumarin and 2‐chloro‐2‐methylbut‐3‐yne [15c]. Very recently [15d], one‐pot Claisen rearrangement/Wittig reaction of 5‐formyl‐6‐hydroxy‐8‐propargyloxy‐2 H ‐chromene with carbethoxymethylenetriphenylphosphorane under MW irradiation led to dipetalolactone. Wittig reactions of this ylide and fused dipyranosalicylaldehyde [15d] under MWs or dipyranobenzo‐1,2‐dione [15e] under reflux in xylene resulted also to dipetalolactone.…”

“…Very recently [15d], one‐pot Claisen rearrangement/Wittig reaction of 5‐formyl‐6‐hydroxy‐8‐propargyloxy‐2 H ‐chromene with carbethoxymethylenetriphenylphosphorane under MW irradiation led to dipetalolactone. Wittig reactions of this ylide and fused dipyranosalicylaldehyde [15d] under MWs or dipyranobenzo‐1,2‐dione [15e] under reflux in xylene resulted also to dipetalolactone. The yields of the aforementioned reactions were moderate.…”

“…The earlier referred methods lead to the synthesis of dipetalolactone under harsh reaction conditions and in not so good yields. The MW irradiation generally has the advantages of lower energy consumption, less reaction times, environmentally friendly process but in this case [14d, 15d] require the troublesome synthesis of the starting material. The one‐pot synthesis reactions are considered as an efficient and greener procedure for the organic synthesis .…”