Maxwell Robert A, Anderson Richard J, Schooley David A
Department of Biochemistry, University of Nevada, Reno, NV 89557, USA.
Anal Biochem. 2002 Jun 1;305(1):40-8. doi: 10.1006/abio.2002.5660.
We report an improved method for the synthesis of high specific activity insect [10-(3)H]juvenile hormones (JH) I, II, and III which affords both enantiomers of each in high optical purity. A synthetic route for JH I was modified to give higher yields and purity. We increased the specific activity of the synthetic [10-(3)H]JHs using normal phase liquid chromatography optimized to give near baseline resolution of [10-(3)H]JHs and unlabeled JHs. Racemic [10-(3)H]JHs and their corresponding diol metabolites were enantiomerically separated using a chiral column eluted with 2-propanol:hexane. Acidic hydration of the unnatural antipode of the [10-(3)H]JHs gives the diol antipode with the same stereochemistry as that from epoxide hydrolase action on the natural JH antipode. The [10-(3)H]JH diol enantiomers can also be resolved with the same chiral column using a more polar solvent. The synthesis of high specific activity chiral ethyl ester analogs of JH I and II can also be accomplished using this synthetic route.
我们报道了一种合成高比活昆虫[10-(³H)]保幼激素(JH)Ⅰ、Ⅱ和Ⅲ的改进方法,该方法能以高光学纯度得到每种保幼激素的两种对映体。对JHⅠ的合成路线进行了改进,以提高产率和纯度。我们使用经过优化的正相液相色谱法提高了合成[10-(³H)]保幼激素的比活,该方法能使[10-(³H)]保幼激素和未标记的保幼激素达到近基线分离。使用用2-丙醇:己烷洗脱的手性柱,对消旋[10-(³H)]保幼激素及其相应的二醇代谢物进行对映体分离。[10-(³H)]保幼激素的非天然对映体的酸水合作用产生的二醇对映体,其立体化学与天然保幼激素对映体经环氧水解酶作用产生的二醇对映体相同。使用极性更强的溶剂,也可以用同一手性柱分离[10-(³H)]保幼激素二醇对映体。使用该合成路线还可以完成JHⅠ和Ⅱ的高比活手性乙酯类似物的合成。