Containing N, P Replaced By Cyanoacrylate Ester Derivatives Synthesis And Biological Activity

Cyanoacrylate, an important class of bioactive compound, is widely applied in agrochemistry. Since 2003, a series of cyanoacrylates including aromatic amines and chiral moiety were synthesized, and their anti-TMV activities and anticancer activities were evaluated. Some of them exhibited good bioactivity.In order to design and synthesize cyanoacrylates derivatives with high bioactivity, started from cyanoacetate, chiral amine, O, O'-dialky phosphite andα-aminophos-phonate moieties were introduced into the structure of cyanoacrylate. 46 title compounds were synthesized, comprising 22 chiral ones, 20 containing phosphonyl moiety and 4 containingα-aminophosphonate moiety cyanoacetates. All compounds were confirmed by IR, ¹H NMR, ¹³C NMR, ³¹P NMR, and elemental analysis. The crystal structure of compound 2b-R was confirmed by X-ray diffraction. From the crystal structure, we found the compound 2b-R was is-isomer. X-ray intensity data is listed as following, the crystal belongs to orthorhombic crystal system, space group is P2(l)2(l)2(l), a = 9.545 (4) nm, b = 10.757 (4) ran, c = 19.011 (8) ran,α= 90°,β= 90°,γ= 90°, Z = 4, V = 1951.9 (13) nm³, Dc = 1.294 mg/m³,μ= 0.092 mm^-1, F(000) = 800,λ= 0.71073 nm.To optimize the reaction conditions, the synthesis of 1b-R and 2p-R were carried out under several conditions. The effects of different solvents, reaction time, and the use of microwave irradiation on the reaction were investigated. The more viable condition was obtained as following: under microwave irradiation of 50 W at 78℃for 20 minutes, compounds 1b-R and 2p-R were synthesized with high yields 83.7%, 52.5% respectively. Compared to the classical method, the present one offers several advantages including mild reaction condition, faster reaction rates, fewer byproducts and higher yields.The result of bioassay showed that most of the compounds exhibit higher antiviral activity against tobacco mosaic virus. Compounds 2p-R, 3a and 3b possess good in vivo curative effects against TMV with inhibitory rates at 500 mg/L of 64.0%, 60.0%, 64.2% respectively. Their curative activities are higher than that of Ninnanmeisu (57.8%). Preliminary studies show that the disease resistance mechanism of bioactive compounds is closely related to the enzyme activities of PAL in Nicotiana tabacum. So it is valuable for us to investigate the mechanism of function in future.