Department of Chemistry and Chemical Biology , Harvard University , 12 Oxford Street , Cambridge , Massachusetts 02138 , United States.
Chemical Biology and Therapeutics Science Program , Broad Institute , 415 Main Street , Cambridge , Massachusetts 02142 , United States.
Org Lett. 2019 Mar 1;21(5):1325-1330. doi: 10.1021/acs.orglett.9b00017. Epub 2019 Feb 14.
The limited scope of DNA-compatible chemistry restricts the types of chemical features that can be incorporated into DNA-encoded libraries (DELs). Here, a method to synthesize DNA-conjugated polycyclic isoxazolidines via a [3 + 2] nitrone-olefin cycloaddition is described. The reaction is compatible with many olefin-containing substrates and diverse N-alkylhydroxylamines. The ability to perform subsequent DNA ligation and PCR amplification was also confirmed. This methodology facilitates the synthesis of DELs containing topographically complex compounds with underexplored chemical features.
DNA 兼容化学的有限范围限制了可掺入 DNA 编码文库 (DEL) 的化学特征类型。在此，描述了一种通过 [3 + 2] 硝酮-烯烃环加成合成 DNA 缀合的多环异噁唑烷的方法。该反应与许多含烯烃的底物和各种 N-烷基羟胺兼容。还证实了进行后续 DNA 连接和 PCR 扩增的能力。该方法促进了含有具有未充分探索的化学特征的拓扑复杂化合物的 DEL 的合成。
