Concise and versatile multicomponent synthesis of multisubstituted polyfunctional dihydropyrroles.
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).
Zhu
Qiuhua
Q
School of Chemistry and Chemical Engineering, South China University of Technology, 381 Wushan Road, Guangzhou, China.
Jiang
Huanfeng
H
Li
Jinghao
J
Liu
Shuwen
S
Xia
Chenglai
C
Zhang
Min
M
D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry
D011758:Pyrroles; C013231:pyrroline