Department of Chemistry, University of Georgia, Athens, Georgia 30602, USA.
J Org Chem. 2011 Aug 19;76(16):6937-41. doi: 10.1021/jo201148h. Epub 2011 Jul 13.
A short and efficient synthesis of cinnoline-fused cyclic enediyne is reported. Richter cyclization of o-(1,3-butadiynyl)phenyltriazene produced 3-alkynyl-4-bromocinnoline. The Sonogashira coupling of the latter with 5-hexyn-1-ol was employed for the introduction of a second acetylenic moiety. The crucial cyclization step was achieved under Nozaki-Hiyama-Kishi conditions. Cinnoline-fused 10-membered ring enediyne is more reactive than corresponding carbocyclic analog and produces good yield of the Bergman cyclization product upon mild heating. This enediyne induces single-strand dDNA scissions upon incubation at 40 °C.
报道了一种简洁高效的稠合环[1,2-a]并[2,3]氮杂环辛二烯的合成方法。邻-(1,3-丁二炔基)苯基三氮烯的 Richter 环化反应生成了 3-炔基-4-溴-1,2-二氮杂萘。后者与 5-己炔-1-醇的 Sonogashira 偶联反应用于引入第二个炔基部分。关键的环化步骤是在 Nozaki-Hiyama-Kishi 条件下完成的。稠合环[1,2-a]并[2,3]氮杂环辛二烯比相应的碳环类似物更具反应活性，在温和加热下可得到 Bergman 环化产物的高产率。该氮杂环辛二烯在 40°C 孵育时会诱导单链 dDNA 断裂。
