Acetohydroxyacid synthase(AHAS) is the target enzyme of several classes of herbicides,such as sulfonylureas and imidazolinones.Now many mutant AHASs with herbicide resistance have emerged along with extensive use of herbicides,therefore it is imperative to understand the detailed interaction mechanism and resistance mechanism so as to develop new potent inhibitors for wild-type or resistant AHAS.With the aid of available crystal structures of the Arabidopsis thaliana(At) AHAS-inhibitor complex,molecular dynamics(MD) simulations were used to investigate the interaction and resistance mechanism directly and dynamically at the atomic level.Nanosecond-level MD simulations were performed on six systems consisting of wild-type or W574L mutant AtAHAS in the complex with three sulfonylurea inhibitors,separately,and binding free energy was calculated for each system using the MM-GBSA method.Comprehensive analyses from structural and energetic aspects confirmed the importance of residue W574,and also indicated that W574L mutation might alert the structural charactersistic of the substrate access channel and decrease the binding affinity of inhibitors,which cooperatively weaken the effective channel-blocked effect and finally result in weaker inhibitory effect of inhibitor and corresponding herbicide resistance of W574L mutant.To our knowledge,it is the first report about MD simulations study on the AHAS-related system,which will pave the way to study the interactions between herbicides and wild-type or mutant AHAS dynamically,and decipher the resistance mechanism at the atomic level for better designing new potent anti-resistance herbicides.
YU ZhiHong,WEN Xin & XI Zhen State Key Laboratory of Elemento-Organic Chemistry
The new synthesis of 10-bromo-α-chamigrene was achieved as follows;6-methyl-5-heptene-2-one was transformed into corresponding thioacetals,and then successively treated with Cp_2Ti(P(OEt)_3)_2.The intermediate reacted with mono-ketal of cyclohexane-1,4-dione,and gave the carbonyl coupling product.It was then transformed into the key intermediateγ-bisabolene via deketalization,Grignard reaction,dehydration and then furnished the target molecule by polyene cyclization,with total yield 2%. All structures were confirmed by ~1H NMR and ^(13)C NMR.The final compound was confirmed by ~1H NMR,^(13)C NMR and MS.
Simple pyrrolidine-azole conjugates have been synthesized and found to be efficient catalysts for asymmetric Michael addition to nitrostyrenes. The identified optimal catalysts, pyrrolidine-azoles 2, 8 and 13, could catalyze the asymmetric Michael addition of a range of Michael donors and nitrostyrenes in high yields (up to 99%) and excellent stereoselectivities (up to 99:1 dr and 97% ee).
A facile and credible strategy was demonstrated to synthesize two new Sn-O clusters 1 and 2 by the reactions of nBu2SnO with esters directly under mild conditions.Cluster 1 crystallizes in the triclinic system,space group P1 with a = 13.054(3),b = 13.137(3),c = 15.077(3) ,α = 80.009(9),β = 77.187(10),γ = 76.075(11)°,Z = 2,V = 2427.3(9) 3,Dc = 1.565 g/cm3,μ(MoKα) = 2.076 mm-1,F(000) = 1152,the final R = 0.0335 and wR = 0.0664 for 9416 observed reflections(I > 2σ(I)).Cluster 2 belongs to the monoclinic system,space group P21/c with a = 13.673(3),b = 13.342(3),c = 16.296(4) ,β = 104.385(5)o,Z = 4,V = 2879.7(10) 3,Dc = 1.347 g/cm3,μ(MoKα) = 1.751 mm-1,F(000) = 1176,the final R = 0.0306 and wR = 0.0706 for 6390 observed reflections(I > 2σ(I)).The crystal structures of the clusters consist of cen-trosymmetric [RCOOSnnBu2OSnnBu2OH)]2 molecules with an almost planar Sn4O4 framework.Each pair of exo-and endo-cyclic tin atoms was linked by one bridge-OH only.In addition,a novel structure of nBu2SnO different from the previous reports was proposed on the basis of 1H-NMR,TG analysis and X-ray diffraction.
