ABSTRACT
The synthesis of a novel fused nitrogen heterocycle, benzoquinolone, for evaluation as a photocleavable protecting group is described for the first time by coupling to model amino acids (alanine, phenylalanine and glutamic acid). Conversion of the phenylalanine ester conjugate to the thionated derivative was accomplished by reaction with Lawesson's reagent. Photocleavage studies of the carbonyl and thiocarbonyl benzoquinolone conjugates in various solvents and at different wavelengths (300, 350 and 419 nm) showed that the most interesting result was obtained at 419 nm for the thioconjugate, revealing that the presence of the thiocarbonyl group clearly improved the photolysis rates, giving practicable irradiations times for the release of the amino acids (less than 1 min).
Subject(s)
Amino Acids/chemistry , Benzoquinones/chemistry , Alanine/chemistry , Chromatography, High Pressure Liquid , Coumarins/chemistry , Esters/chemistry , Glutamic Acid/chemistry , Light , Magnetic Resonance Spectroscopy , Molecular Structure , Phenylalanine/chemistry , Photochemical Processes , Photolysis , Quinolones/chemistry , Solvents/chemistry , Spectrophotometry, Ultraviolet , TemperatureABSTRACT
A novel fluorescent amino acid, L-4-chloromethylcoumarin-6-yl-alanine, was obtained from tyrosine by a Pechmann reaction. The assembly of the heterocyclic ring at the tyrosine side chain could be achieved before or after incorporation of tyrosine into a dipeptide, and amino acid and dipeptide ester conjugates were obtained by coupling to a model N-protected alanine. The behaviour of one of the fluorescent conjugates towards irradiation was studied in a photochemical reactor at different wavelengths (254, 300, 350 and 419 nm). The photoreaction course in methanol/HEPES buffer solution (80:20) was followed by HPLC/UV monitoring. It was found that the novel unnatural amino acid could act as a fluorescent label, due to its fluorescence properties, and, more importantly, as a photoactivable unit, due to the short irradiation times necessary to cleave the ester bond between the model amino acid and the coumarin-6-yl-alanine.
Subject(s)
Alanine/analogs & derivatives , Coumarins/chemistry , Tyrosine/chemistry , Alanine/chemical synthesis , Alanine/chemistry , Coumarins/chemical synthesis , Fluorescence , Magnetic Resonance Spectroscopy , Molecular Structure , Photochemical Processes , Spectrometry, FluorescenceABSTRACT
In order to evaluate the application of quinolone as a new photocleavable protecting group, in comparison with coumarin, a series of model phenylalanine conjugates were prepared by reaction with chloromethylated O and N heterocycles. The photophysical properties of the resulting ester conjugates were evaluated as well as the photosensitivity under irradiation at 250, 300, 350, and 419 nm. The results obtained showed that the quinolone conjugates were readily photolysed, with complete release of the amino acid in short irradiation times and could be considered a new addition to the family of photocleavable protecting groups for the carboxylic acid function of amino acids.
