Tandem Thio-Michael Addition/Remote Lactone Activation of 5-Hydroxymethylfurfural-Derived δ-Lactone-Fused
Rafael F A Gomes1, Joao M J M Ravasco1, Késsia H S Andrade1
1Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisboa, Portugal.
Abstract:
The creation of structurally diverse chemical entities from fairly simple biorefinery products remains a challenge. In this work 5-hydroxymethylfurfural (HMF) was identified as a key synthon for preparing highly complex cyclopentenones (CP) via tandem 1,4-addition/elimination/remote lactone activation to external O- and N-nucleophiles in δ-lactone-fused-CPs hotspots. This scaffold was also reactive enough to be incorporated into model cysteine-peptides in low concentrations, paving the way to a potential translation generating complexity in the synthesis of small peptides. The new enones also exhibited activity against intraerythrocytic Plasmodium falciparum (IC50 =1.32 μm).
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