PDF(Pubmed)
Abstract：
Highly diastereoselective methods for the synthesis of two series of regioisomeric polynuclear dispyroheterocyclic compounds with five or six chiral centers, comprising moieties of pyrrolidinyloxindole and imidazo[4,5-e]thiazolo[3,2-b]-1,2,4-triazine of linear structure or imidazo[4,5-e]thiazolo[2,3-c]-1,2,4-triazine of angular structure, have been developed on the basis of a [3+2] cycloaddition of azomethine ylides to functionalized imidazothiazolotriazines. Depending on the structure of the ethylenic component, cycloaddition proceeds as an anti-exo process for linear derivatives, while cycloaddition to angular ones resulted in a syn-endo diastereomer. Novel pathways of isomerization for the synthesized anti-exo products upon treatment with sodium alkoxides have been found, which resulted in two more series of diastereomeric dispiro[imidazothiazolotriazine-pyrrolidin-oxindoles] inaccessible with the direct cycloaddition reaction. For the first series, the inversion of the configuration of one stereocenter, i.e., C-4\' atom of the pyrrolidine cycle, (epimerization) was established. For the second one, configuration of the obtained diastereomer formally corresponded to the syn-endo approach of the azomethine ylide in the case of cycloaddition to the ethylenic component.
摘要：
高度非对映选择性方法，用于合成具有五个或六个手性中心的两个系列的区域异构多核二氢杂环化合物，包含线性结构的吡咯烷基氧吲哚和咪唑并[4,5-e]噻唑并[3,2-b]-1,2,4-三嗪或角形结构的咪唑并[4,5-e]噻唑并[2,3-c]-1,2,4-三嗪的部分，已经在甲亚胺叶立德与官能化的咪唑并噻唑三嗪的[32]环加成的基础上开发。根据烯属组分的结构，环加成作为线性导数的反外型过程进行，而环加成到角度的环加成导致顺式-内非对映体。已发现用醇钠处理合成的抗外切产物异构化的新途径，这导致另外两个系列的非对映体二氢[咪唑并噻唑三嗪-吡咯烷-羟吲哚]无法通过直接环加成反应获得。对于第一个系列，一个立体中心的配置的反转，即，吡咯烷环的C-4原子，（差向异构化）已建立。对于第二个，在环加成到烯属组分的情况下，获得的非对映异构体的构型形式上对应于甲亚胺叶立德的顺式-内方法。
