Title:Multicomponent Reactions Applied to Total Synthesis of Biologically
Active Molecules: A Short Review
Volume: 23
Issue: 11
Author(s): Juliana A. dos Santos*, Pedro P. de Castro, Kleber T. de Oliveira, Timothy J. Brocksom and Giovanni W. Amarante*
Affiliation:
- Department of Chemistry, Federal University of Juiz de Fora, Juiz de Fora, 36036-900, MG, Brazil
- Department of Chemistry, Federal University of Juiz de Fora, Juiz de Fora, 36036-900, MG, Brazil
Keywords:
Multicomponent reactions, total synthesis, one-pot processes, medicinal chemistry, complex intermediates, fine chemicals.
Abstract: Multicomponent reactions (MCRs) are processes in which three or more starting materials
are combined in the same reaction vessel, forming an adduct that contains all or most of the
atoms of the starting materials. MCRs are one-pot processes that provide attractive advantages for
the total synthesis of target molecules. These reactions allow rapid access to structurally complex
adducts from particularly simple starting materials. Moreover, MCRs are generally intrinsically associated
with principles of green syntheses, such as atom economy, minimization of isolation, and
purification of synthetic intermediates, leading to large solvent economies and avoiding the production
of large amounts of reaction waste. Thus, synthetic routes employing multicomponent reactions
are generally more convergent, economical and often allow higher overall yields. In total synthesis,
the use of MCRs has been mainly applied in the preparation of key advanced intermediates. Progress
in the use of MCRs in total synthesis has been described over the last decades, including not
only classical MCRs reactions (e.g. isocyanide-based transformations), but also non-traditional multicomponent
reactions. Furthermore, reports concerning stereoselective multicomponent transformations
are still scarce and present further development opportunities. This review aims to provide a
general overview of the application of MCRs as key steps in the rapid preparation of structurally
complex derivatives and fine chemicals. In special, some selected examples have been successfully
applied for medicinal purposes. Finally, in some representative cases, either key intermediates formed
during the reaction vessel or corresponding transition states have been disclosed in order to
provide insights into the reaction mechanisms.
