Toshima K, Ohta K, Kano T, Nakamura T, Nakata M, Kinoshita M, Matsumura S
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Japan.
Bioorg Med Chem. 1996 Jan;4(1):105-13. doi: 10.1016/0968-0896(95)00170-0.
The molecular design and chemical synthesis of novel enediyne molecules related to the neocarzinostatin chromophore (1), and their chemical and DNA cleaving properties are described. The 10-membered enediyne triols 16-18 were effectively synthesized from xylitol (10) in a short step, and found to be quite stable when handled at room temperature. The representative and acylated enediyne 16 was cycloaromatized by 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in cyclohexa-1,4-diene-benzene to give the benzenoid product 21 through a radical pathway. On the other hand, the enediyne 16 was cycloaromatized by diethylamine in dimethyl sulfoxide-Tris-HCl, pH 8.5 buffer to afford another benzenoid product 22 as a diethylamine adduct through a polar pathway. Furthermore, the enediynes 16-18 were found to exhibit guanine-specific DNA cleavage under weakly basic conditions with no additive.
描述了与新制癌菌素发色团（1）相关的新型烯二炔分子的分子设计和化学合成，以及它们的化学性质和DNA切割特性。十元烯二炔三醇16 - 18可通过木糖醇（10）经短步骤高效合成，并且发现在室温下处理时相当稳定。代表性的酰化烯二炔16在环己-1,4 - 二烯 - 苯中被1,8 - 二氮杂双环[5.4.0]十一碳 - 7 - 烯（DBU）环芳构化，通过自由基途径得到苯型产物21。另一方面，烯二炔16在二甲亚砜 - Tris - HCl（pH 8.5缓冲液）中被二乙胺环芳构化，通过极性途径得到另一种苯型产物22，为二乙胺加合物。此外，发现烯二炔16 - 18在无添加剂的弱碱性条件下表现出鸟嘌呤特异性DNA切割。
