Department of Chemistry, Perm State University, ul. Bukireva, 15, 614990 Perm, Russia.
Molecules. 2022 Aug 17;27(16):5257. doi: 10.3390/molecules27165257.
4-Acyl-1-pyrrole-2,3-diones fused at []-side with a heterocyclic moiety are suitable platforms for the development of a hetero-Diels-Alder-reaction-based, diversity-oriented approaches to series of skeletally diverse heterocycles. These platforms are known to react as oxa-dienes with dienophiles to form angular 6/6/5/6-tetracyclic alkaloid-like heterocycles and are also prone to decarbonylation at high temperatures resulting in generation of acyl(imidoyl)ketenes, bidentate aza- and oxa-dienes, which can react with dienophiles to form skeletally diverse products (angular tricyclic products or heterocyclic ensembles). Based on these features, we have developed an approach to two series of skeletally diverse 4-1,3-oxazines (tetracyclic alkaloid-like 4-1,3-oxazines and 5-heteryl-4-1,3-oxazines) via a hetero-Diels-Alder reaction of 4-acyl-1-pyrrole-2,3-diones fused at []-side with cyanamides. The products of these transformations are of interest for drug discovery, since compounds bearing 4-1,3-oxazine moiety are extensively studied for inhibitory activities against anticancer targets.
4-酰基-1-吡咯-2,3-二酮与杂环部分在 []-位稠合，是开发基于杂 Diels-Alder 反应的、多样性导向方法合成一系列骨架多样的杂环的合适平台。这些平台已知作为氧二烯与亲二烯体反应，形成角型 6/6/5/6-四环生物碱样杂环，并且在高温下也容易脱羰生成酰基（亚氨酰基）烯酮、双齿氮杂和氧二烯，它们可以与亲二烯体反应，形成骨架多样的产物（角型三环产物或杂环组合）。基于这些特点，我们通过 4-酰基-1-吡咯-2,3-二酮与氰酰胺在 []-位稠合的杂 Diels-Alder 反应，开发了两种骨架多样的 4-1,3-恶嗪（四环生物碱样 4-1,3-恶嗪和 5-杂基-4-1,3-恶嗪）系列。这些转化的产物对药物发现很有意义，因为含有 4-1,3-恶嗪部分的化合物广泛研究其对抗癌靶标的抑制活性。
