César Raposo

A CYCLOHEXANE SPACER FOR PHOSPHATE RECEPTORS

Abstract A cyclohexane tricarboxylic acid is shown to be a good spacer for phosphate guests. The combination of 8-aminochromenone-2-carboxamide groups with the cyclohexane spacer leads to a versatile receptor which sets six hydrogen bonds with either phosphonic acids or phosphates. Large association constants are obtained for this receptor in DMSO and methanol when tetraalkylammonium phosphates are used as guests.

Imidazolidinone intermediates in prolinamide-catalyzed aldol reactions

The reaction between acetone and 4-nitrobenzaldehyde catalyzed by aniline prolinamide 1 was studied in depth. Working in different solvents with equimolar amounts of reagents and monitoring the reaction by 1H NMR, we detected and identified several imidazolidinones, such as those of the acetone 4, the aldol products 5a and 5b, and aldehydes 10a and 10b. According to our results, these compounds could influence the reaction rate and diminish product enantioselectivity. Furthermore, acetone imidazolidinone 4 was seen to react with 4-nitrobenzaldehyde to furnish the aldol product 3. This reaction can be catalyzed by different nucleophiles and acids. In fact, strong acids such as camphorsulfonic or trifluoroacetic acid, convert imidazolidinones into iminium salts and afford more enantioselective aldol reactions when different aromatic prolinamides are used. Enantiomeric excesses of ca. 82% are reached.

Synthesis of Monoacylated Derivatives of 1,2- Cyclohexanediamine. Evaluation of their Catalytic Activity in the Preparation of Wieland−Miescher Ketone†

Ureas, carbamoyl derivatives, amides, and sulfonamides can be easily prepared from the strained (R,R)-cylohexanediamine urea (1) in high yield, leaving a free amino group that shows good catalytic activity in intramolecular aldol condensations. The preparation of Wieland-Miescher ketone has been studied with these catalysts.

CHIRAL RECOGNITION OF TARTARIC ACID DERIVATIVES WITH CHROMENONE-BENZOXAZOLE RECEPTORS AND A SPIROBIFLUORENE SPACER

Abstract The combination of a spirobifluorene spacer with two chromenone-amino-benzoxazole binding arms affords a chiral cleft type receptor. Due to the strong chiral recognition, resolution of the receptor racemic mixture can be achieved by means of a silica gel TLC plate impregnated with optically pure dibenzoyl tartaric acid. Slow complex formation on the 1 H-NMR scale with this host at −10°C allows observation of different signals for free and complex guests in 1 H-NMR.

Readily available chromenone receptors for carboxylates

Abstract Several carboxylate group receptors able to bind syn and anti electron lone pairs have been prepared making use of an aminochromenone fragment. Symmetric ureas and sulfuryl amides permit the establishment of four linear hydrogen bonds with the carboxylate. The flat geometry of the sulfuryl amides complexes and the higher acidity of their hydrogens yield the best association constants.

Urinary levels of regenerating islet-derived protein III β and gelsolin differentiate gentamicin from cisplatin-induced acute kidney injury in rats

A key aspect for the clinical handling of acute kidney injury is an early diagnosis, for which a new generation of urine biomarkers is currently under development including kidney injury molecule 1 and neutrophil gelatinase-associated lipocalin. A further diagnostic refinement is needed where one specific cause among several potentially nephrotoxic insults can be identified during the administration of multidrug therapies. In this study we identified increases in regenerating islet-derived protein III beta (reg IIIb) and gelsolin as potential differential urinary markers of gentamicins nephrotoxicity. Indeed, urinary levels of both reg IIIb and gelsolin distinguish between the nephrotoxicity caused by gentamicin from that caused by cisplatin where these markers were not increased by the latter. Reg IIIb was found to be overexpressed in the kidneys of gentamicin-treated rats and excreted into the urine, whereas urinary gelsolin originated from the blood by glomerular filtration. Our results illustrate an etiological diagnosis of acute kidney injury through analysis of urine. Thus, our results raise the possibility of identifying the actual nephrotoxin in critically ill patients who are often treated with several nephrotoxic agents at the same time, thereby providing the potential for tailoring therapy to an individual patient, which is the aim of personalized medicine.

Catalysis of nucleophilic addition of pyrrolidine to 2-(5H)-furanone through chromenone cleft-type receptors

Abstract Several H-bonding receptors are shown to significantly catalyze the nucleophilic addition of pyrrolidine to 2-(5 H )-furanone to a significant extent. Combination of these receptors with a sulfonamide group affords a further increase in the catalytic effect of these molecules.

A receptor for aromatic acids and amides

A dinitrotoluic residue has been introduced onto an hydrogen bonding aromatic acid receptor to achieve stacking and charge-transfer interactions. This new receptor shows large differences in association constants with aromatic guests in CDCl3 ranging from 1.6 × 103 with isophthalic acid methyl ester to 1.5 × 106 with p-dimethylamino benzoic acid.

Three complexing agents for ureas and formamides

Abstract Three cleft type hydrogen bonding receptors were prepared, with slightly different geometries due to the presence of either methylene, oxygen, or sulfur. All three are able to complex urea, one with the methylene group being the best suited. Benzyl formamide, probably due to its smaller cleft, is better associated to the oxygen compound.

Improved receptors for dibutylmalonic acid

Abstract New molecular receptors with a dibenz[c,h]acridine skeleton bearing functional groups complementary to dibutylmalonic acid have been developed.