Efficient access to sp super(3)-rich tricyclic amine scaffolds through Diels-Alder reactions of azide-containing silyloxydienes

The preparation of sp super(3)-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...

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Bibliographic Details
Published in:Tetrahedron 2016-06, Vol.72 (26), p.3766-3774
Main Authors: McLeod, Michael C, Aube, Jeffrey
Format: Article
Language:English
Subjects:
Alkaloids
Amines
Carbon
Decks
Diels-Alder reactions
Gain
Libraries
Scaffolds
Online Access:Get full text
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Summary:The preparation of sp super(3)-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 sp super(3) carbon centers.
ISSN:0040-4020
DOI:10.1016/j.tet.2016.03.016