Eymery Mathias, Tran-Nguyen Viet-Khoa, Boumendjel Ahcène
Université Grenoble Alpes, INSERM, LRB, 38000 Grenoble, France.
EMBL Grenoble, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble, France.
Pharmaceuticals (Basel). 2021 Nov 5;14(11):1127. doi: 10.3390/ph14111127.
Diversity-Oriented Synthesis (DOS) represents a strategy to obtain molecule libraries with diverse structural features starting from one common compound in limited steps of synthesis. During the last two decades, DOS has become an unmissable strategy in organic synthesis and is fully integrated in various drug discovery processes. On the other hand, natural products with multiple relevant pharmacological properties have been extensively investigated as scaffolds for ligand-based drug design. In this article, we report the amino dimethoxyacetophenones that can be easily synthesized and scaled up from the commercially available 3,5-dimethoxyaniline as valuable starting blocks for the DOS of natural product analogs. More focus is placed on the synthesis of analogs of flavones, coumarins, azocanes, chalcones, and aurones, which are frequently studied as lead compounds in drug discovery.
多样性导向合成（DOS）是一种从一种常见化合物出发，通过有限的合成步骤获得具有多样结构特征的分子库的策略。在过去的二十年中，DOS已成为有机合成中不可或缺的策略，并完全融入到各种药物发现过程中。另一方面，具有多种相关药理特性的天然产物已被广泛研究，作为基于配体的药物设计的支架。在本文中，我们报道了可以从市售的3,5-二甲氧基苯胺轻松合成并放大规模的氨基二甲氧基苯乙酮，作为天然产物类似物DOS的有价值起始原料。更多的重点放在黄酮、香豆素、氮杂环辛烷、查耳酮和噢哢类似物的合成上，这些化合物在药物发现中经常作为先导化合物进行研究。
