A One‐Pot Synthesis of Symmetrical and Unsymmetrical Dipeptide Ureas

Abstract

We describe a flexible and high yielding synthesis of 1,3‐disubstituted ureas that allows for the construction of both symmetrical and unsymmetrical dipeptide ureas, including easy access to 13C‐labelled ureas, from amino acids and carbon dioxide at atmospheric pressure.

One-step preparation of enantiopure l- or d-amino acid benzyl esters avoiding the use of banned solvents

“…Coming to the methionine ester 9a, it is to be noted that the older preparation in refluxing benzene has a 56% yield and is supported by melting point and optical rotation as analytical data (Kawasaki 1980), while the more recent one in refluxing toluene has a 75% yield but provides neither melting point nor optical rotation (Fayad 2015). In both cases, the enantiomeric excess is an unknown issue.…”

“…On the other hand, histidine, asparagine, glutamine and threonine benzyl esters tosylates are just cited as reactants (Kempf 1991;Zhao 2009;Abiko 1983;Nishizawa 1977;Bose 1982) but, to the best of our knowledge, their preparations have never been individually described, while those of tryptophan and arginine are, in different respects, problematic (Arai 1983;Magnus 1989;Biondini 2010;Dorman 1976) and cysteine benzyl ester tosylate is unknown. Of the remaining proline and methionine benzyl esters tosylates, for which one and two preparations with only partial characterizations are reported respectively (Dai 2009;Kawasaki 1980;Fayad 2015), we decided to include methionine (9). Therefore, we have considered the preparation of the benzyl esters tosylates 1a-8a and, in addition, the methionine benzyl ester tosylate 9a, after verifying that literature methods prescribe, for the nine esters, the use of refluxing benzene, toluene, carbon tetrachloride or benzyl alcohol itself regardless of safety and of racemization and provide very few or no analytical data on the enantiomer systems formed by the products and on their enantiomeric composition (Chart 2).…”

Coumarin-Based Dual Inhibitors of Human Carbonic Anhydrases and Monoamine Oxidases Featuring Amino Acyl and (Pseudo)-Dipeptidyl Appendages: In Vitro and Computational Studies

“…This strategy is not only valuable for the rational design of peptide-based substrates and inhibitors for protein targets that will eventually be developed as therapeutics but also provides fundamental insights into the complexity of mutual dynamic interactions involving peptide ligands and their macromolecular acceptors, which leads to pharmacophore optimization and eventually translation of the peptide mimic into a small molecule drug. In this regard, the introduction of a carbonyldiamide (urea) NH-CO-NH linkage such as a peptide bond surrogate is a widely established method that exploits the structural and physico-chemical features of this moiety to improve target affinity and selectivity, as well as stability and bioavailability properties of the resulting pseudo-peptide compared to those of the native molecule [22][23][24][25]. Due to the delocalization of the nitrogen lone pair onto the urea carbonyl, which involves both NH functionalities, ureas present with reduced electrophilicity, enhanced chemical stability, and protease resistance relative to amides.…”

Graphene Oxide (GO) as Sustainable Heterogeneous Carbocatalyst for Synthesis of Organic Carbamates Using Urea and Alcohols under Mild Reaction Conditions

“…[29][30][31] Generally these carbamates compounds are produced from alcohols and amines in presence of phosgene (COCl 2 ) as carbonylating source. [32,33] As phosgene is very harmful chemicals so the mentioned methodology suffers from eco-friendliness. This method has low atom economy, produced large quantity of toxic byproducts and required long reaction.…”