Synthesis And Biological Activities Of3-Acetyltetramic Acid Oxime Ether Derivatives

Hundreds of natural tetramic acids with diversified structures have been isolated from land and ocean organism and were found to exhibit antitumor, antiviral, antibacterial and herbicidal activities. The pyrrolidine-2,4-dione ring was modified and a lot of tetramic acid derivatives among of which possessed good biological activities were synthesized. In order to find more novel compounds showing better biological activities, two series tetramic acid oxime ether derivatives were designed and synthesized, and the fungicidal and herbicidal activities of them were also tested. Three single crystal structures of the compounds were obtained to further confirm the structures.First, synthesis and biological activities of novel3-acetyl-5-arylidene-tetramic acid oxime ether derivatives were studied. The compounds (Z)-3-acetyl-5-arylidene-4-hydroxypyrroline-2-ones were prepared by the reaction of3-acyl tetramic acid which was synthesized with the glycine as the starting materials with substituted benzaldehydes.(Z)-3-acetyl-5-arylidene-4-hydroxypyrroline-2-ones were reacted with O-alkyl hydroxylamines to afford twenty four3-acetyl-5-arylidene tetramic acid oxime ether derivatives(Ⅰ) respectively. The structures of these compounds were confirmed by IR,1H NMR, MS and elemental analysis. The single crystals of Ie and Ij suitable for collecting data on the X-ray diffraction machine were obtained. Both the crystals were in triclinic system with space group P-1, The unit cell parameters of Ie as follows:a=7.440(5)A,6=9.486(6)A, c=12.745(8)A, a=69.035(7)°,β=89.336(7)°, γ=74.838(8)°, Z=2, Dc=1.235g.cm-3, V=807.4(9)A3, F(000)=320. The unit cell parameters of Ij as follows: a=8.8536(15)A,b=9.0461(15)A, c=16.010(3)A, α=105.610(3)°,β=92.074(3)°, γ=115.446(2)°, Z=2, Dc=1.281g.cm-3, V=1098.1(3)A3, F(000)=448. The herbicidal activities of the target compounds were determined with Brassica napus and Echinochloa crusgalli (L.) Beauv at a concentration of100μtg/mL. The result showed that the herbicidal activities of all compounds were quite weak. The fungicidal activities were tested by radial growth inhibition method using Fusarium gramineaum, Rhizoctonia cerealis, and Colletotrichum orbiculare at a concentration of100μg/mL. The results showed that most of the title compounds exhibited noticeable fungicidal activities against Colletotrichum orbiculare and a certain degree of fungicidal activities against Fusarium gramineaum and Rhizoctonia cerealis. The compounds la, In, and Ip displayed the remarkable activities against Colletotrichum orbiculare with EC50values of1.15,30.43and40.13μg/mL, respectively.Second, synthesis and biological activities of novel3-acetyl-l-alkyl-tetramic acid oxime ether derivatives were studied. The starting material ethyl bromoacetate was reacted with alkylamines to afford N-alkylglycine ethyl ester which was treated to abtain3-acetyl-1-alkyl-tetramic acid via three-steps reactions.3-Acetyl-l-alkyl-4-hydroxypyrroline-2-ones were reacted with O-alkyl hydroxylamines afforded twenty3-acetyl-l-alkyl tetramic acid oxime ether derivatives(Ⅱ) respectively. Structures of all new compounds were confirmed by IR,1H NMR, MS and elemental analysis. The single crystal of Ⅱr was abtained to further determain the structure of title compounds. The crystal was in monoclinic system with space group C2/c, and the unit cell parameters as follows:a=32.78(9)A,b=5.195(14)A, c=18.025(5)A, β=102.734(3)°, Z=8, Dc=1.235g.cm-3, V=2993.8(14)A3,F(000)=1200. The results of herbicidal activities showed that these compounds exhibited noticeable inhibition against the root of Brassica napus and Echinochloa crusgalli (L.) Beauv, but weak inhibition against the bud of Echinochloa crusgalli (L.) Beauv. The inhibition of compound Ⅱs against the root of Brassica napus and Echinochloa crusgalli (L.) Beauv was78.1%and85.2%, respectively. The results of fungicidal activities indicated these compounds exhibited noticeable fungicidal activities against Fusarium gramineaum, Rhizoctonia cerealis and Colletotrichum orbiculare at a concentration of100μg/mL. Fungicidal activities of most of these compounds against Colletotrichum orbiculare were more than50%, Ⅱm with the highest activity up to70.0%. The inhibition of all these compounds against three test fungi was better than tenuazonic acid.