The Ugi Three‐Component Reaction; a Valuable Tool in Modern Organic Synthesis

Abstract

The Ugi three component reaction (U‐3CR) is a variation of the famous Ugi reaction, discovered almost 60 years ago. Today it is somehow neglected, compared to the classical variation, although the α‐aminoamides, derived from this reaction, have been utilized as inhibitors for various targets and even commercial drugs, offering improved pharmacokinetic properties. In this review, we are describing the scope and limitations of the reaction with a special focus on the developed catalytic protocols, the bioactive compounds, and drugs which are based on the reaction and finally the post modifications that have been reported in order to access drug‐like and privileged scaffolds. A special focus is given to the 3D solid state conformations of the U‐3CR derivatives.

In Silico Design and Selection of New Tetrahydroisoquinoline-Based CD44 Antagonist Candidates

“…MCR are one-pot reactions in which two or more starting materials are used simultaneously; thus, most of the atoms from the initial building blocks are incorporated into the final product of the reaction [35,36]. The Ugi four-component tetrazole synthesis [28,29] and Ugi three-component reaction [30] are well described, easy to perform, and have been suggested as synthesis methods for diverse drug-like molecules [36]. Additionally, we selected building blocks that are commercially available at low-cost, which will allow compound synthesis and activity evaluation in further studies.…”

“…To facilitate the synthesis of our compounds in subsequent research, we decided to use multicomponent reactions (MCR) synthesis routes. Considering the characteristics of the THQ-containing small molecules co-crystallized with mCD44HAbd, we implemented the Ugi four-component tetrazole synthesis [28,29] and Ugi three-component reaction [30] for our CCC experiments. For each MCR route, we obtained 84,096 different compounds (Scheme 1).…”

Click-based conjugated microporous polymers as efficient heterogeneous photocatalysts for organic transformations

“…The C(sp 3 )-H α-carbamoylation of N,N-dimethylanilines, namely the Ugi multicomponent reaction, is a widely studied organic transformation and can give straightforward access to α-amino amides, [47][48][49][50] which are prevalent chemicals in organic synthesis. 51 However, most studies have focused on the reactions of alkyl isocyanides with N,N-dimethylanilines, while the research on the reactions of aryl isocyanides with N,N-dimethylanilines is rarely involved. Due to the good porous properties and strong visible light absorption abilities of the Ta-Ths, we decided to investigate their photocatalytic activities in the C(sp 3 )-H α-carbamoylation of N,Ndimethylaniline and their derivatives with aryl isocyanides via the oxidative Ugi-type reaction.…”

Fluorene-Based Multicomponent Reactions

“…Often, the resulting -aminoacylamides which are present in many bioactive compounds and commercially available drugs, lead to improved pharmacokinetic/pharmacodynamic properties, including oral bioavailability and water solubility, due to the incorporation of a basic amine. 53 We therefore investigated the U-3CR that gave the -aminoacylamides 6a and 6b (Figure 2). We employed secondary amines in an aqueous solution of formaldehyde with no catalysts, additives, or other solvents to access caine-type adducts.…”