Department of Biochemistry, Division of Chemistry , UT Southwestern Medical Center , 5323 Harry Hines Blvd. , Dallas , Texas 75390-0938 , United States.
Org Lett. 2019 Feb 1;21(3):648-651. doi: 10.1021/acs.orglett.8b03777. Epub 2019 Jan 17.
Dysoline, a novel chromone alkaloid isolated from Dysoxylum binectariferum, was reported to have selective cytotoxicity for HT1080 fibrosarcoma cells (IC of 0.21 μM). Given the scarcity of natural material, a concise synthesis of (+)-dysoline was developed, allowing for further biological evaluation. An enantioselective nucleophile-catalyzed aldol lactonization formed the piperidine ring with control of relative and absolute stereochemistry. Construction of the C6-chromone core with complete regioselectivity was achieved using a Danheiser benzannulation.
从醉鱼草属植物中分离得到的新型色酮生物碱地索林，对 HT1080 纤维肉瘤细胞具有选择性细胞毒性（IC 为 0.21 μM）。鉴于天然产物的稀缺，开发了简洁的（+）-地索林全合成路线，以进一步进行生物学评价。对映选择性亲核体催化的Aldol 内酯化反应以控制相对和绝对立体化学形成了哌啶环。使用 Danheiser 苯并环化反应实现了 C6-色酮核心的完全区域选择性构建。
