Department of Chemistry, Wrocław University of Environmental and Life Sciences, Norwida 25, 50-375 Wrocław, Poland.
Enzyme Microb Technol. 2011 Apr 7;48(4-5):326-33. doi: 10.1016/j.enzmictec.2010.12.007. Epub 2010 Dec 21.
The metabolism of δ-iodo-γ-lactones containing cyclohexane ring with an increasing number of methyl substituents in Absidia cylindrospora was studied and seven metabolites were isolated as the products of biotransformations of these substrates. They were formed as the result of various dehalogenation pathways and four of them (hydroxylactones and epoxylactone) turned out to be new compounds. The conversion of substrates ranged from 60% to 90% and the highest conversion was observed for the iodolactone with an unsubstituted cyclohexane ring. The products were fully characterized by the spectroscopic methods and for the hydroxylactone with gem-dimethyl group at C-5 and hydroxylactone with trimethylcyclohexane system the crystal structures were obtained. The main products formed in the process of hydrolytic dehalogenation were δ-hydroxy-γ-lactones with the hydroxy group located cis in relation to lactone moiety. In case of lactone with 4,4,6-trimethylcyclohexane system the dehydrohalogenation followed by the epoxidation of double bond was also observed. One of the metabolites 4,5-epoxy-2,2,6-trimethyl-9-oxabicyclo[4.3.0]nonan-8-one was formed in the sequence of three reactions: hydroxylation at C-5, translactonization and intramolecular nucleophilic substitution of the iodine by the hydroxy group. Some of the isolated products of transformation of the iodolactone with trimethylcyclohexane system were obtained as the single enantiomers. The application of fungi studied to the dehalogenation of iodolactones could be a useful method in the production of new metabolites with oxygen-containing functional groups with antifeedant activity.
研究了链霉菌属中含环己烷环且甲基取代基逐渐增多的δ-碘代-γ-内酰胺的代谢情况，从这些底物的生物转化产物中分离出了 7 种代谢产物。它们是通过各种脱卤化途径形成的，其中 4 种（羟基内酰胺和环氧内酰胺）是新化合物。底物的转化率从 60%到 90%不等，未取代环己烷环的碘代内酰胺转化率最高。产物通过光谱方法进行了充分的表征，对于 C-5 位具有偕二甲基基团的羟基内酰胺和具有三甲基环己烷体系的羟基内酰胺，还获得了晶体结构。水解脱卤化过程中形成的主要产物是δ-羟基-γ-内酰胺，其中羟基位于内酯部分的顺式位置。对于具有 4,4,6-三甲基环己烷体系的内酯，还观察到双键的脱氢卤化和随后的环氧化。一种代谢产物 4,5-环氧-2,2,6-三甲基-9-氧杂双环[4.3.0]壬烷-8-酮是通过三个反应序列形成的：C-5 羟化、转内酯化和碘被羟基的分子内亲核取代。三甲基环己烷体系的碘代内酰胺转化的一些分离产物是作为单一对映异构体获得的。所研究的真菌对碘代内酰胺的脱卤化作用可以成为生产具有抗食活性的含氧官能团的新代谢物的有用方法。
