Concise and versatile multicomponent synthesis of multisubstituted polyfunctional dihydropyrroles.

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Synthetic Chemistry

Background:

• Dihydropyrroles are important heterocyclic compounds with diverse applications.
• Efficient synthesis of highly substituted dihydropyrroles remains a challenge.
• Antiviral drug discovery requires novel chemical scaffolds.

Purpose of the Study:

• To develop concise and high-yield synthetic routes for tetra- and pentasubstituted polyfunctional dihydropyrroles.
• To explore the potential of these novel compounds as antiviral agents.
• To establish easy access to diverse dihydropyrrole libraries.

Main Methods:

• One-pot multicomponent reactions (MCRs) involving but-2-ynedioates, amines, and aldehydes.
• Two distinct reaction pathways utilizing domino hydroamination/nucleophilic addition/amidation-cyclization and hydroamination/amidation/intramolecular cyclization/imine-enamine tautomerization sequences.
• Structure confirmation using single-crystal X-ray diffraction.

Main Results:

• High yields of tetra- and pentasubstituted polyfunctional dihydropyrroles were achieved.
• Two novel synthetic methodologies were established.
• 22 tested compounds demonstrated significant in vitro activity against HIV-1, with IC(50) values in the micromolar range (38-58 μM).

Conclusions:

• The developed MCRs provide efficient and versatile access to novel dihydropyrrole derivatives.
• The synthesized dihydropyrroles exhibit promising anti-HIV-1 activity.
• These findings open avenues for further development of dihydropyrrole-based antiviral drugs.