Multistep Synthesis of 1,2,4-Oxadiazoles via DNA-Conjugated Aryl Nitrile Substrates
Multistep Synthesis of 1,2,4-Oxadiazoles via DNA-Conjugated Aryl Nitrile Substrates
复制标题
DOI：
10.1021/acs.bioconjchem.9b00188
复制
发表时间：
2019-05-01
影响因子：
4.7
通讯作者：
Matzuk, Martin M.
中科院分区：
文献类型：
--
作者：
Du, Huang-Chi;Bangs, Madison C.;Matzuk, Martin M.
已经开发出在 DNA-化学缀合物上合成 3,5-二取代 1,2,4-恶二唑的多步骤方案。一组六种 DNA 连接的芳基腈被羟胺转化为相应的偕胺肟，然后用一系列芳基和脂肪族羧酸进行 O-酰化。 O-酰基偕胺肟在 pH 9.5 硼酸盐缓冲液中于 90 摄氏度下加热 2 小时进行环化脱水后，观察到所需恶二唑产物的转化率为 51-92%，其中 O-酰基偕胺肟的裂解为主要副产物。所报告的方案为合成以恶二唑为核心的 DNA 编码化学库铺平了道路。
A multistep protocol for the synthesis of 3,5-disubstituted 1,2,4-oxadiazoles on DNA-chemical conjugates has been developed. A set of six DNA-connected aryl nitriles were converted to corresponding amidoximes with hydroxyl-amine followed by the O-acylation with a series of aryl and aliphatic carboxylic acids. After cyclodehydration of the O-acyl amidoximes by heating at 90 degrees C in pH 9.5 borate buffer for 2 h, the desired oxadiazole products were observed in 51-92% conversion with the cleavage of O-acylamidoximes as the major side-product. The reported protocol paves the way for the synthesis of oxadiazole core-focused DNA-encoded chemical libraries.