title: Efficient access to sp3-rich tricyclic amine scaffolds through Diels-Alder reactions of azide-containing silyloxydienes.
abstract: 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 sp3carbon centers.
authors.affiliation: The University of Kansas Center of Excellence in Chemical Methodologies and Library Development (KU-CMLD), 2034 Becker Drive, Del Shankel Structural Biology Center, Lawrence, Kansas 66047, United States.
authors.forename: Michael C
authors.initials: MC
authors.lastname: McLeod
authors.affiliation: The University of Kansas Center of Excellence in Chemical Methodologies and Library Development (KU-CMLD), 2034 Becker Drive, Del Shankel Structural Biology Center, Lawrence, Kansas 66047, United States.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Aubé
keywords: Diels-Alder cycloaddition; Parallel synthesis; polycyclic heterocycles