A series of 19 related dihydrobenzofuran lignans and benzofurans was obtained by a biomimetic reaction sequence involving oxidative dimerization of p-coumaric, caffeic, or ferulic acid methyl esters, followed by derivatization reactions. All compounds were evaluated for potential anticancer activity in an in vitro human disease-oriented tumor cell line screening panel that consisted of 60 human tumor cell lines arranged in nine subpanels, representing diverse histologies. Leukemia and breast cancer cell lines were relatively more sensitive to these agents than were the other cell lines. Compounds 2c and 2d, but especially 2b (methyl (E)-3-¿2-(3, 4-dihydroxyphenyl)-7-hydroxy-3-methoxycarbonyl-2, 3-dihydro-1-benzofuran-5-ylprop-2-enoate), the dimerization product of caffeic acid methyl ester, containing a 3',4'-dihydroxyphenyl moiety and a hydroxyl group in position 7 of the dihydrobenzofuran ring, showed promising activity. The average GI(50) value (the molar drug concentration required for 50% growth inhibition) of 2b was 0.3 microM. Against three breast cancer cell lines, 2b had a GI(50) value of <10 nM. Methylation, reduction of the double bond of the C(3)-side chain, reduction of the methoxycarbonyl functionalities to primary alcohols, or oxidation of the dihydrobenzofuran ring to a benzofuran system resulted in a decrease or loss of cytotoxic activity. Compound 2b inhibited mitosis at micromolar concentrations in cell culture through a relatively weak interaction at the colchicine binding site of tubulin. In vitro it inhibited tubulin polymerization by 50% at a concentration of 13 +/- 1 microM. The 2R, 3R-enantiomer of 2b was twice as active as the racemic mixture, while the 2S,3S-enantiomer had minimal activity as an inhibitor of tubulin polymerization. These dihydrobenzofuran lignans (2-phenyl-dihydrobenzofuran derivatives) constitute a new group of antimitotic and potential antitumor agents that inhibit tubulin polymerization.

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The title compound has been synthesised in racemic form by a biomimetic reaction sequence. The two enantiomers were resolved by column chromatography of one of the synthetic intermediates. On the basis of CD results a tentative absolute configuration for the synthetic enantiomers and natural 3',4-di-0methylcedrusin is proposed.Sungre de drug0 (dragon's blood), a blood-red latex produced by various South American Croton species, is widely used in local medicine for its wound-healing properties and as an anticancer agent . 3',4-Di-0-methylcedrusin or 3-[2-( 3,4-dimethoxyphenyl)-3-hydroxymethyl-7-methoxy-2,3-dihydro-1 -benzofuran-5-yl]propan-l-015 has been shown to be one of the active principles being a wound healing agent and an inhibitor of thymidine incorporation in endothelial cells. p 2 Results and discussionRacemic 5 has been synthesised as shown in Scheme 1. Near quantitative esterification of ferulic acid was achieved with a heterogeneous polymer catalyst to give methyl ferulate 1 the biomimetic 6,7 oxidative coupling of which, in the presence of silver oxide,8 to generate the dihydrobenzofuran skeleton is the crucial step in the reaction sequence. Compound 2, shown unequivocally by X-ray crystallography to have a transconfiguration,' upon attempted methylation with diazomethane or with dimethyl sulfate gave complex mixtures of unidentified compounds. With methyl iodide, however, it gave compound 3, although to avoid the formation of, for instance, C-methylated side products (the formation of a product with a molecular weight of 442 has been demonstrated by DCI-mass spectrometry) the reaction time has to be kept relatively short; this results in relatively low product yields. Hydrogenation of the double bond of 3 in the presence of Pd-C yields compound 4 almost quantitatively, although, prolonged reaction times or large amounts of catalyst have to be avoided, since they result in ring opening of the dihydrofuran ring. LiAlH, reduction of both ester functions of 4 gave 3',4-di-O-methylcedrusin 5.The structures of compounds 2 to 5 were established on the basis of 'H NMR-, 13C NMR-, COSY, and HETCOR-spectral evidence (Tables 1 and 2). Both natural 3',4-di-O-rnethylcedrusin and the racemic ' F1 m id 2: -I XI 9

Pentaerythritol diphosphonate melaminedicyandiamide-formaldehyde resin salt, a novel macromolecular intumescent flame retardants (IFR), was synthesized, and its structure was a caged bicyclic macromolecule containing phosphorus characterized by IR, NMR and element analysis. The flame retardancy and thermal behavior of a new IFR system for epoxy resin were investigated by LOI, UL-94 test, TG, and IR. Activation energy for the decomposition of samples was obtained using Kissinger equation. 25% of weight of IFR were doped into epoxy resin to get 27.5 of LOI and UL 94 V-0. The TG curves and IR spectra show that IFR decreases the initial decomposition temperature and the maximum weight loss rate of epoxy resin, and enhances the thermal stability of epoxy resin at high temperatures and char yield. The activation energy for epoxy resin containing IFR was decreased by 44.8 kJ/ mol, which shows that IFR can catalyze decomposition of epoxy resin.