School of Chemistry & Biochemistry, School of Biological Sciences , Georgia Institute of Technology , 901 Atlantic Drive , Atlanta , Georgia 30332 , United States.
Org Lett. 2018 Jun 1;20(11):3233-3236. doi: 10.1021/acs.orglett.8b01093. Epub 2018 May 16.
A class of ester-amide oxanorbornadiene (EA-OND) molecules was developed to release alcohol cargos by succinimide formation upon addition of a thiol reagent. The resulting ring-closed adducts undergo further fragmentation by retro-Diels-Alder reaction to release a furan moiety in a manner similar to oxanorbornadiene diesters. The rates of each of these fragmentation pathways in the same medium were found to be sensitive to the steric nature of the amide substituent. Alcohol release was much faster in protic solvents than in aprotic ones, suggesting that this system may be useful for rapid response to thiols in biological environments. Accordingly, the attachment and thiol-dependent release of cholesterol was characterized as an example of the manipulation of a drug-like cargo.
一类酯酰胺降冰片烯（EA-OND）分子通过加成硫醇试剂形成琥珀酰亚胺来释放醇 cargo。所得闭环加合物通过逆狄尔斯-阿尔德反应进一步断裂，以类似于降冰片二酯的方式释放呋喃部分。在相同介质中，这些断裂途径的速率均对酰胺取代基的空间性质敏感。在质子溶剂中，醇的释放速度比在非质子溶剂中快得多，这表明该体系可能有助于快速响应生物环境中的硫醇。因此，胆固醇的附着和硫醇依赖性释放被表征为药物样 cargo 操纵的一个例子。
