Skeletal Diversity by Ugi Four-Component Coupling Reaction and Post-Ugi Reactions

Oikawa, Masato; Naito, Shinya; Sasaki, Makoto

doi:10.3987/com-07-s(u)8

Cited by 9 publications

(5 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There are many classical documented post-transformation reactions, i.e., Pictet–Spengler cyclization, intramolecular Diels–Alder reaction, Mitsunobu reaction and acyl migration, Knovenagel condensation, amide reduction, metathesis reaction, Ugi–Ugi, and Ugi–Petasis etc. ,,,− The strategies entailing intramolecular variants of the Ugi reaction and post condensation modifications of the Ugi product inspire the development of methodology that enables concise access to diverse pharmacologically relevant scaffolds. These Ugi variants indeed afforded enticing structures for further diversification.…”

Section: Multicomponent Reactions For the Synthesis Of Tetrazolesmentioning

confidence: 99%

Tetrazoles via Multicomponent Reactions

2019

View full text Add to dashboard Cite

Tetrazole derivatives are a prime class of heterocycles, very important to medicinal chemistry and drug design due to not only their bioisosterism to carboxylic acid and amide moieties but also to their metabolic stability and other beneficial physicochemical properties. Although more than 20 FDA-approved drugs contain 1H- or 2H-tetrazole substituents, their exact binding mode, structural biology, 3D conformations, and in general their chemical behavior is not fully understood. Importantly, multicomponent reaction (MCR) chemistry offers convergent access to multiple tetrazole scaffolds providing the three important elements of novelty, diversity, and complexity, yet MCR pathways to tetrazoles are far from completely explored. Here, we review the use of multicomponent reactions for the preparation of substituted tetrazole derivatives. We highlight specific applications and general trends holding therein and discuss synthetic approaches and their value by analyzing scope and limitations, and also enlighten their receptor binding mode. Finally, we estimated the prospects of further research in this field.

show abstract

Section: Multicomponent Reactions For the Synthesis Of Tetrazolesmentioning

confidence: 99%

Tetrazoles via Multicomponent Reactions

2019

View full text Add to dashboard Cite

show abstract

“…16 These mimics were synthesized in good yields via a three-step procedure involving an Ugi-4CR, the chemoselective introduction of the allyl groups on the Ugi products, followed by RCM. The 13-and 14-membered cycles 29a and 29b respectively were obtained in cis-geometry while the trans-isomer was predominant for the 15-membered cycle 29c (Scheme 7).…”

Section: Ugi-ring Closing Metathesis (Rcm) Approachmentioning

confidence: 99%

“…Utilizing Grubbs' catalyst carbon, oxygen, nitrogen, and sulfur containing dienes can be cyclized to form functionalized cycloalkenes. [13][14][15][16][17] In recent years, this approach has been widely utilized for synthesizing libraries of diversity-oriented templates, which resemble natural products or find multiple applications in peptidomimetics. A recent review by Orru and co-workers 7 deals with this topic and the reader is advised to read both reviews to have a better overview.…”

Section: Ugi-ring Closing Metathesis (Rcm) Approachmentioning

confidence: 99%

“…Likewise, for the synthesis of macrocyclic (more than 12 membered) rings, Oikawa and co-workers have developed a straightforward approach based on the ring closing metathesis of allylated Ugi adducts 28. 16 These mimics were synthesized in good yields via a three-step procedure involving an Ugi-4CR, the chemoselective introduction of the allyl groups on the Ugi products, followed by RCM. The 13-and 14-membered cycles 29a and 29b respectively were obtained in cis-geometry while the trans-isomer was predominant for the 15-membered cycle 29c (Scheme 7).…”

Section: Ugi-ring Closing Metathesis (Rcm) Approachmentioning

confidence: 99%

See 1 more Smart Citation

Metal-mediated post-Ugi transformations for the construction of diverse heterocyclic scaffolds

et al. 2015

View full text Add to dashboard Cite

The Ugi-4CR is by far one of the most successful multicomponent reactions leading to high structural diversity and molecular complexity. However, the reaction mostly affords a linear peptide backbone, enabling post-Ugi transformations as the only solution to rigidify the Ugi-adduct into more drug like species. Not surprisingly, the development of these transformations, leading to new structural frameworks, has expanded rapidly over the last few years. As expected, palladium-catalyzed reactions have received the foremost attention, yet other metals, particularly gold complexes, are fast catching up. This tutorial review outlines the developments achieved in the past decade, highlighting the modifications that are performed in a sequential or domino fashion with emphasis on major concepts, synthetic applications of the derived products as well as mechanistic aspects.

show abstract

“…302 The 4CR constructs the basic framework of the structure, which, through a variety of additional transformations, can be converted to 12-to 16-membered macrocycles (for example 191, Scheme 11.25, building block contributions to the molecule and RCM site and catalyst indicated).…”

Section: Multicomponent Reactions (Mcr)mentioning

confidence: 99%

The Synthesis of Macrocycles for Drug Discovery

Peterson¹

2014

Macrocycles in Drug Discovery

View full text Add to dashboard Cite

Despite the attractive nature of macrocyclic compounds for use in new pharmaceutical discovery, applications have been hindered due to the lack of appropriate synthetic methods, in particular for the construction of libraries of such molecules. However, over the last decade, a number of effective and versatile methodologies suitable for macrocyclic scaffolds have been developed and applied successfully. These include classical coupling and substitution reactions, ring-closing metathesis (RCM), cycloaddition (“click”) chemistry, multicomponent reactions (MCR), numerous organometallic-mediated processes and others. This chapter presents a comprehensive compilation of these strategies and provides examples of their use in drug discovery, along with a description of those approaches that have proven effective for the assembly of macrocyclic libraries suitable for screening.

show abstract

Skeletal Diversity by Ugi Four-Component Coupling Reaction and Post-Ugi Reactions

Cited by 9 publications

References 7 publications

Tetrazoles via Multicomponent Reactions

Tetrazoles via Multicomponent Reactions

Metal-mediated post-Ugi transformations for the construction of diverse heterocyclic scaffolds

The Synthesis of Macrocycles for Drug Discovery

Contact Info

Product

Resources

About