Tetra- and pentasubstituted polyfunctional dihydropyrroles have been concisely synthesized in high yields by two different processes of the one-pot multicomponent reactions (MCRs) of but-2-ynedioates 1, amines 2, and aldehydes 3 at room temperature or at 70 degrees C. The first one involves a domino hydroamination/nucleophilic addition/amidation-cyclization process and leads to the formation of tetrasubstituted polyfunctional dihydropyrroles 4. The second undergoes hydroamination/amidation/intramolecular cyclization/imine-enamine tautomerization sequence and results in pentasubstituted products 5. The structures of 4 and 5 were confirmed by single-crystal X-ray diffraction. These novel methodologies provide easy access to diversely multisubstituted polyfunctional dihydropyrrole libraries. The primary biological screening in vitro against HIV-1 has shown that 22 tested compounds have exhibited significant activity with IC(50) in micromolar range (38-58 microM).