Tipranavir analogous 3-sulfonylanilidotetronic acids: new synthesis and structure-dependent anti-HIV activity

Sulfonamide-containing tetronic acids 1, structural analogues of the HIV-1 protease inhibitor tipranavir, were synthesised in five steps including a microwave-assisted Claisen rearrangement of cinnamyl tetronates and a modified Charette cyclopropanation of the so-formed 3-allyltetronic acids. Compounds 1 with two non-H residues (R1, R2) at C-5 of the tetronate core exhibited structure-dependent antiviral activity in two HIV strains. Derivatives 1c (R1=R2=Me, R3=Cl) and 1d (R1,2=(CH2)5, R3=Me) were most active (IC50<10 μM) in the sensitive strain HIVNL4-3.