The reaction of papaverine with a series of Baran DiversinatesTM is reported. Although the yields were low, it was possible to synthesize a small biodiscovery library using this plant alkaloid as a scaffold for late-stage C-H functionalization. Ten papaverine analogues (2-11), including seven new compounds, were synthesized. An unexpected radical-induced exchange reaction is reported where the dimethoxybenzyl group of papaverine was replaced by an alkyl group. This side reaction enabled the synthesis of additional novel fragments based on the isoquinoline scaffold, which is present in numerous natural products. Possible reasons for the poor yields in the DiversinateTM reactions with this particular scaffold are discussed.
Keywords: DiversinateTM; biodiscovery; late-stage functionalization; library; medicinal chemistry; natural product; papaverine; scaffold; sulfinate.