Wimmer Zdenek, Pechová Lucie, Sīle Laura, Saman David, Jedlicka Pavel, Wimmerová Martina, Kolehmainen Erkki
Institute of Experimental Botany AS CR, Laboratory of Chemistry, Vídenská 1083, CZ-14220 Prague 4, Czech Republic.
Bioorg Med Chem. 2007 Nov 15;15(22):7126-37. doi: 10.1016/j.bmc.2007.07.022. Epub 2007 Aug 22.
A series of the protected alkyl glycosides 5a/5b-12a/12b was synthesized from the parent isomeric alcohols (insect juvenile hormone bioanalogs; juvenoids), 4-[4'-(2''-hydroxycyclohexyl)methylphenoxy]-3-methyl-but-2-enoic acid ethyl ester (1a/1b-4a/4b; racemic structures) and (1a-4a; enantiopure structures). Cadmium carbonate was used as a promoter of this Koenigs-Knorr reaction, and the products were obtained in 82-92% yields. Deprotection of the carbohydrate functionality of 5a/5b-12a/12b was carefully performed using ethanolysis in the presence of zinc acetate, due to the presence of another ester functionality in the aglycone part of the molecule of protected alkyl glycosides. Resulting alkyl glycosides 13a/13b-20a/20b (diastereoisomeric mixtures) and 13a-20a (enantiopure compounds), biochemically activated hormonogenic compounds (juvenogens), were obtained in 82-93% yields. Finally, chiral HPLC separation of the diastereoisomeric mixtures of alkyl glycosides was applied to get sufficient quantities of the respective enantiomers 13b-20b of the alkyl glycosides for their structure elucidation and (13)C chemical shift assignment by (1)H and (13)C NMR spectroscopy. Partial introductory entomological screening tests of the target alkyl glycosides 13a/13b-20a/20b were performed on the red firebug (Pyrrhocoris apterus). The results of this biological testing clearly demonstrated the time-extended effect of several juvenogens on P. apterus due to their biochemical activation, i.e., hydrolysis of the juvenogen molecule, which results in liberation of the biologically active juvenoid in the insect organism.
一系列受保护的烷基糖苷5a/5b - 12a/12b由母体异构醇(昆虫保幼激素类似物;保幼激素)、4-[4'-(2''-羟基环己基)甲基苯氧基]-3-甲基-丁-2-烯酸乙酯(1a/1b - 4a/4b;外消旋结构)和(1a - 4a;对映体纯结构)合成。碳酸镉用作该柯尼希斯-克诺尔反应的促进剂,产物收率为82 - 92%。由于受保护烷基糖苷分子的苷元部分存在另一个酯官能团,在乙酸锌存在下通过乙醇解小心地对5a/5b - 12a/12b的碳水化合物官能团进行脱保护。得到的烷基糖苷13a/13b - 20a/20b(非对映异构体混合物)和13a - 20a(对映体纯化合物),即生物化学活化的激素原性化合物(保幼激素原),收率为82 - 93%。最后,应用烷基糖苷非对映异构体混合物的手性高效液相色谱分离法,以获得足够量的烷基糖苷各自的对映体13b - 20b,用于其结构解析以及通过¹H和¹³C NMR光谱对¹³C化学位移进行归属。对目标烷基糖苷13a/13b - 20a/20b进行了部分初步昆虫学筛选试验,以红蝽(Pyrrhocoris apterus)为对象。该生物学测试结果清楚地表明,几种保幼激素原对红蝽具有时间延长效应,这是由于它们的生物化学活化,即保幼激素原分子的水解,导致昆虫体内释放出生物活性保幼激素类似物。