Diversity by divergence: Solution-phase parallel synthesis of a library of N-diversified 1-oxa-7-azaspiro[4.5]decan-2-yl-propanes and -butanes.
The synthesis of a 162-member compound library derived from a single precursor via a multistage divergence strategy is described. Divergence is sequentially introduced in three ways: (1) by early preparation of two separable spirocyclic diastereomers, (2) by elaboration of each spirocyclic diastereomer to a different scaffold using four Horner-Emmons-Wadsworth reagents, and (3) by employing three different modes of nitrogen diversification with each scaffold to afford the final compounds. This 2 diastereomers × 4 reagents × 3 modes of diversification strategy leads to 24 unique synthetic pathways that ultimately afforded, in parallel format, the 162-compound set.
Center for Chemical Methodologies and Library Development, The University of Kansas , 2034 Becker Drive, Lawrence, Kansas 66047, United States.
Sarvesh
S
Kumar
Paul D
PD
Thornton
Conrad
C
Santini
D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry; D054852:Small Molecule Libraries / Q000138:chemical synthesis* / Q000737:chemistry; D012996:Solutions; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D005663:Furans; D010880:Piperidines; D054852:Small Molecule Libraries; D012996:Solutions; D013141:Spiro Compounds