Synthesis of Fluorenes and Their Related Compounds from Biaryls and Meldrum’s Acid Derivatives

A new synthetic method for preparing fluorenes from amino group-containing biaryls and Meldrum’s acid derivatives was developed. The reaction proceeded without a catalyst and loss of functional groups. The corresponding...

pH-Dependent Selective Colorimetric Detection of Proline and Hydroxyproline with Meldrum’s Acid-Furfural Conjugate

Activated 2-furfural gives intense color formation when reacted with amines, due to a ring opening reaction cascade that furnishes a conjugated molecular system. Unique colorimetric characteristic of this reaction makes it an interesting candidate for developing chemosensors operating in visible range. Among many activated 2-furfural derivatives, Meldrum’s acid furfural conjugate (MAFC) recently gained significant interest as colorimetric chemosensor. MAFC has been explored as selective chemosensor for detecting amines in solution, secondary amines on polymer surfaces and even nitrogen rich amino acids (AA) in aqueous solution. In this work, the pH dependency of MAFC-AA reaction is explored. It was found that proline gives an exceptionally fast colored reaction at pH 11, whereas at other pHs, no naked eye color product formation was observed. The reaction sequence including ring opening reaction upon nucleophilic addition of cyclic amine of proline resulting in a conjugated triene was confirmed by NMR titrations. The highly pH dependent reaction can e.g., potentially be used to detect proline presence in biological samples. An even more intense color formation takes place in the reaction of natural proline derivative 4-hydroxyproline. The detection limit of proline and 4-hydroxyproline with MAFC solution was found to be 11 µM and 6 µM respectively.

Integration of C-Acylation in the Solid-Phase Synthesis of Peptides and Peptidomimetics employing Meldrum’s Acid, Phosphorus and Sulfur Ylides

Modification of native peptides to peptidomimetics is an important goal in medicinal chemistry and requires in many cases the integration of C-acylation steps involving amino acids with peptide synthesis. Many classical C-acylation protocols involving Claisen condensations or the use of ylides are not compatible with peptide synthesis, mostly due to the requirement of strong bases leading to epimerization or deprotection of peptides. Meldrum’s acid as well as several specific phosphorus and sulfur ylides, however, are acidic enough to provide reactive C-nucleophiles at mildly basic conditions tolerated during peptide synthesis. This review provides an overview of peptide-compatible C-acylations of Meldrum´s acid, phosphorus and sulfur ylides and their application in the medicinal chemistry of peptides.