Isocyanide Multicomponent Reactions on Solid Phase: State of the Art and Future Application

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Synthetic Chemistry

Background:

• Drug discovery relies on structural diversity.
• Multicomponent reactions (MCRs) offer efficient synthesis of complex molecules.
• Isocyanide-based MCRs provide multiple diversification points.

Purpose of the Study:

• To review solid-phase syntheses of small molecules using isocyanide-based MCRs.
• To highlight the advantages of solid-phase MCRs in library synthesis and odor reduction.
• To outline unexplored potential of MCRs in drug discovery.

Main Methods:

• Focus on solid-phase synthesis strategies.
• Review of Ugi four-component reaction (Ugi-4CR) as the predominant method.
• Inclusion of Passerini and Groebke-Blackburn-Bienaymé reactions.

Main Results:

• Solid-phase MCRs enable efficient preparation of chemical libraries for biological screening.
• Elimination of isocyanide odor is a significant advantage of solid-phase approaches.
• Ugi-4CR is the most frequently employed reaction in reported syntheses.

Conclusions:

• Solid-phase isocyanide-based MCRs are valuable tools for generating structural diversity in drug discovery.
• Further exploration of MCRs in areas like chiral synthesis and DNA-encoded libraries is warranted.
• The full potential of MCRs for creating novel molecular architectures remains largely untapped.