Wang Kaikai, Zhou Wenwen, Jia Jun, Ye Junwei, Yuan Mengxin, Yang Jie, Qi Yonghua, Chen Rongxiang
School of Pharmacy, Xinxiang University, Xinxiang 453000, China.
Jilin Province Product Quality Supervision and Inspection Institute, Changchun 130012, China.
Molecules. 2023 Sep 22;28(19):6761. doi: 10.3390/molecules28196761.
Substrate-controlled diversity-oriented synthesis of polycyclic frameworks via [4 + 2] and [3 + 2] annulations between ninhydrin-derived Morita-Baylis-Hillman (MBH) adducts and 3,4-dihydroisoquinolines under similar reaction conditions have been developed. The reaction provides diversity-oriented synthesis of a series of novel and structurally complex spiro multi heterocyclic skeletons in good yields (up to 87% and 90%, respectively) with excellent diastereoselectivities (up to >25:1 ). In particular, the switchable [4 + 2] and [3 + 2] annulation reactions are controlled by tuning the hydroxyl protecting group on the ninhydrin-derived MBH adduct to deliver structural diverse spiro[indene-2,2'-[1,3]oxazino[2,3-]isoquinoline] and spiro[indene-2,1'-pyrrolo[2,1-]isoquinoline], respectively. Furthermore, the relative configuration and chemical structure of two kinds of cycloadducts were confirmed through X-ray diffraction analysis.
通过茚三酮衍生的森田-贝利斯-希尔曼（MBH）加合物与3,4-二氢异喹啉在相似反应条件下进行的[4 + 2]和[3 + 2]环化反应，实现了底物控制的多环骨架的多样性导向合成。该反应以良好的产率（分别高达87%和90%）和优异的非对映选择性（高达>25:1）提供了一系列新颖且结构复杂的螺多杂环骨架的多样性导向合成。特别地，可切换的[4 + 2]和[3 + 2]环化反应通过调节茚三酮衍生的MBH加合物上的羟基保护基来控制，分别得到结构多样的螺[茚-2,2'-[1,3]恶嗪并[2,3 - ]异喹啉]和螺[茚-2,1'-吡咯并[2,1 - ]异喹啉]。此外，通过X射线衍射分析确定了两种环加成产物的相对构型和化学结构。
