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In this manuscript we report: 1) for the first time our findings on the (3 + 2) methodology, 2) expanded substrate scope for the (4 + 3) annulation, 3) the identification of one of these compounds, JWU-A021, as a potent GLP-1 secretagogue, and 4) experimental evidence indicating that JWU-A021 likely operates in the intestinal L-cells by elevating the intracellular [Ca 2+ ] by means of activating the Transient Receptor Potential Ankyrin 1 channel (TRPA1) 4