Chemical investigation of Beouverio felina,a marine-derived entomopathogenic fungus,obtained two new destruxin hexadepsipeptides(1 and 2)containing an/.-Ala^(5)residue instead of the usual A/-Me-L-Ala^(5).Interestingl...Chemical investigation of Beouverio felina,a marine-derived entomopathogenic fungus,obtained two new destruxin hexadepsipeptides(1 and 2)containing an/.-Ala^(5)residue instead of the usual A/-Me-L-Ala^(5).Interestingly,the presence of the/.-Ala^(5)residue enabled two slowly-exchanging solution conformers with cis/trons(ILE^(3))-(A/-Me-Val^(4))amide bond for 1 and 2 with 1.5:1 and 1:1 cis/trans ratios,respectively,while only the conformer with c/s amide bond was found in the solid-state.The solution and solid-state conformers were studied by NMR,X-ray diffraction and solution and solid-state ECD measurements,as well as by TDDFT-ECD calculations.Structural(conformational)parameter-activity correlations suggested that the extended destruxin geometry with the preferred c/s(ILE^(3))-(A/-Me-Val^(4))bond probably resulted in improved bioactivity and reduced toxicity for the destruxin class.This was the first report on the interconversion phenomenon of cis/trans amide bonds of destruxin class,which could give insights in the development of bioactive destruxin agents with lower toxicity.展开更多
基金the National Natural Science Foundation of China(31270104)the NSFC-Shandong Joint Fund for Marine Science Research Centers(U1606403)+2 种基金the Oceanographic Data Center at IOCAS.T.K.and A.M.thank the National Research,Development and Innovation Office(NKFI K120181 and FK134653)the Governmental Information-Technology Development Agency(KIFU for CPU time)B.-G.W.also acknowledged the support of the Taishan Scholar project from Shandong province.
文摘Chemical investigation of Beouverio felina,a marine-derived entomopathogenic fungus,obtained two new destruxin hexadepsipeptides(1 and 2)containing an/.-Ala^(5)residue instead of the usual A/-Me-L-Ala^(5).Interestingly,the presence of the/.-Ala^(5)residue enabled two slowly-exchanging solution conformers with cis/trons(ILE^(3))-(A/-Me-Val^(4))amide bond for 1 and 2 with 1.5:1 and 1:1 cis/trans ratios,respectively,while only the conformer with c/s amide bond was found in the solid-state.The solution and solid-state conformers were studied by NMR,X-ray diffraction and solution and solid-state ECD measurements,as well as by TDDFT-ECD calculations.Structural(conformational)parameter-activity correlations suggested that the extended destruxin geometry with the preferred c/s(ILE^(3))-(A/-Me-Val^(4))bond probably resulted in improved bioactivity and reduced toxicity for the destruxin class.This was the first report on the interconversion phenomenon of cis/trans amide bonds of destruxin class,which could give insights in the development of bioactive destruxin agents with lower toxicity.
