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在1-取代-四氢-β-咔啉的C1位创建不对称中心的合成途径——综述

Synthetic pathways to create asymmetric center at C1 position of 1-substituted-tetrahydro-β-carbolines - a review.

作者信息

Asif Md Moaz Ahmed, Lisa Susmita Roy, Qais Nazmul

机构信息

Department of Pharmacy, Faculty of Science & Engineering, University of Information Technology & Sciences Holding 190, Road 5, Block J, Baridhara, Maddha Nayanagar, Vatara Dhaka-1212 Bangladesh.

Department of Chemistry, Syracuse University Syracuse NY 13244 USA.

出版信息

RSC Adv. 2024 Sep 19;14(41):29827-29847. doi: 10.1039/d4ra05961a. eCollection 2024 Sep 18.

DOI:10.1039/d4ra05961a
PMID:39301229
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11411349/
Abstract

The 2,3,4,9-tetrahydro-1-pyrido[3,4-]indoles or tetrahydro-β-carbolines (THβCs) are tricyclic compounds that are found in various natural sources that exhibit a wide range of important pharmacological activities. Chiral 1-substituted-THβCs, which have an asymmetric center at C1, have attained significant interest due to their possible Monoamine Oxidase (MAO) inhibitory activity, benzodiazepine receptor binding activity, and antimalarial effectiveness against chloroquine-resistant . This review highlights and summarizes various novel stereoselective approaches to introduce chirality at the C1 position of 1-substituted-THβCs in good yield and enantiomeric excess (ee) or diastereomeric excess (de). These methods include the Pictet-Spengler reaction, chiral auxiliary, Asymmetric Transfer Hydrogenation (ATH) with chiral catalysts, asymmetric addition reaction, and enzymatic catalysis. The syntheses of chiral THβCs are reviewed comprehensively, emphasizing their role in drug development from 1977 to 2024.

摘要

2,3,4,9-四氢-1-吡啶并[3,4-]吲哚或四氢-β-咔啉（THβCs）是一类三环化合物，存在于多种天然来源中，具有广泛的重要药理活性。在C1位具有不对称中心的手性1-取代-THβCs，因其可能具有的单胺氧化酶（MAO）抑制活性、苯二氮䓬受体结合活性以及对氯喹耐药疟原虫的抗疟效果而备受关注。本综述重点介绍并总结了各种新颖的立体选择性方法，这些方法能够以良好的产率和对映体过量（ee）或非对映体过量（de）在1-取代-THβCs的C1位引入手性。这些方法包括 Pictet-Spengler 反应、手性助剂、使用手性催化剂的不对称转移氢化（ATH）、不对称加成反应以及酶催化。本文全面综述了手性THβCs的合成，重点强调了它们在1977年至2024年药物开发中的作用。

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