Efficient access to sp³-rich tricyclic amine scaffolds through Diels-Alder reactions of azide-containing silyloxydienes

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• 作者：Michael C. McLeod ; Jeffrey Aubé ; ; ^&dagger ; ; ^{jaube@unc.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Parallel synthesis ; Diels&ndash ; Alder cycloaddition ; Polycyclic heterocycles
• 刊名：Tetrahedron
• 出版年：2016
• 出版时间：30 June 2016
• 年：2016
• 卷：72
• 期：26
• 页码：3766-3774
• 全文大小：580 K

文摘

The preparation of sp³-rich scaffolds to obtain more natural product–like libraries for incorporation into screening decks is challenging. Here, we describe the use of a Diels–Alder reaction between an enone and an azide-containing silyloxydiene to gain efficient access to complex tricyclic amine scaffolds. Derivatization of these scaffolds provided a library of 80 amines, amides, sulfonamides, quinolines and indolenines, all in >20 mg quantities and >90% purities. These library compounds displayed properties more similar to alkaloid natural products than to drugs and commercial drug-like libraries, as shown by a high proportion of sp³ carbon centers.