Synthesis of 3,4-Dihydropyrimidin(thio)one Containing Scaffold: Biginelli-like Reactions

Abstract

The interest in 3,4-dihydropyrimidine-2(1H)-(thio)ones is increasing every day, mainly due to their paramount biological relevance. The Biginelli reaction is the classical approach to reaching these scaffolds, although the product diversity suffers from some limitations. In order to overcome these restrictions, two main approaches have been devised. The first one involves the modification of the conventional components of the Biginelli reaction and the second one refers to the postmodification of the Biginelli products. Both strategies have been extensively revised in this manuscript. Regarding the first one, initially, the modification of one of the components was covered. Although examples of modifications of the three of them were described, by far the modification of the keto ester counterpart was the most popular approach, and a wide variety of different enolizable carbonylic compounds were used; moreover, changes in two or the three components were also described, broadening the substitution of the final dihydropyrimidines. Together with these modifications, the use of Biginelli adducts as a starting point for further modification was also a very useful strategy to decorate the final heterocyclic structure.

Investigating the efficacy of green solvents and solvent-free conditions in hydrogen-bonding mediated organocatalyzed model reactions

“…53 In medicinal chemistry, DHPMs are regarded as privileged structures owing to the presence of the DHPM component in numerous drug candidates. 54 Enantioselective synthesis holds a crucial position in the pharmaceutical industry, as individual enantiomers may exhibit varying behaviours under physiological conditions. 55,56 Accordingly, we next focused on investigating the effect of greener solvents on the asymmetric Biginelli reaction catalysed by the MacMillan TiPSY catalyst (III), as initially reported by Gong and co-workers.…”

The untold story of starch as a catalyst for organic reactions

“…164 There are many biologically active pyrimidine-based compounds and alongside purine, pyrimidine is one of the building blocks of DNA and RNA. 165,166 These structures can be found in several candidate drugs. 167 To facilitate the preparation of these important heterocyclic compounds, Foroughifar's research group introduced magnetic starch support loaded with aspartic acid (Scheme 48).…”

Hydroaminoalkyl Functionalization of Pyrimidin‐2(1H)‐ones by Visible Light Organophotocatalysis: A Radical Approach to Biginelli‐Type Dihydropyrimidines

“…Mono‐ or unsubstituted ureas are generally used to access the corresponding 1( N )‐mono(un)substituted pyrimidines. Over the last few decades, this reaction has been significantly improved in terms of yield, scope, and durability thanks to the many variations and modifications developed (including multistep methodologies) [5,6,13–15] . However, despite these achievements, control of site‐selectivity on the pyrimidine ring remains a synthetic challenge.…”

“…Over the last few decades, this reaction has been significantly improved in terms of yield, scope, and durability thanks to the many variations and modifications developed (including multistep methodologies). [5,6,[13][14][15] However, despite these achievements, control of site-selectivity on the pyrimidine ring remains a synthetic challenge. A second approach (Scheme 1b) is based on the addition of Cnucleophile onto the C=CÀ C=N endocyclic system of the pyrimidin-2(1H)-one scaffold, either at the C4position (direct addition to the C=N bond) or at the C6-position (1,4-conjugate addition).…”