RESUMEN
We have employed a tandem Sonogashira/annulation reaction between 5-iodocytosine derivatives and terminal alkynes to yield the fluorescent bicyclic nucleobase pyrrolcytosine. Pyrrolocytosine bearing substituents only on the pyrrole ring are conveniently synthesized from 5-iodocytosine. Water soluble pyrrolocytosines are being investigated as reporter groups in SNP analysis.
Asunto(s)
Citosina/análogos & derivados , Química Farmacéutica/métodos , Citosina/síntesis química , Citosina/química , Modelos Químicos , Conformación Molecular , Sondas de Ácido Nucleico/química , Sondas de Ácido Nucleico/farmacología , Polimorfismo de Nucleótido Simple , Análisis de Secuencia de ADN/métodos , Agua/químicaRESUMEN
We report recent developments in the optimization of a submonomer synthesis of peptide nucleic acid based on the Fukuyama-Mitsunobu reaction. The key steps in the submonomer synthesis are the installation of an appropriately protected 2-aminoethyl group on the alpha-nitrogen of an amino acid and its subsequent acylation with a protected nucleobase derivative. The aggressive alkylation conditions require a scheme of maximal protection for the nucleobases and that is proposed herein for the pyrimidines.
Asunto(s)
Ácidos Nucleicos de Péptidos/síntesis química , Aminoácidos , Citosina/química , Indicadores y Reactivos , Nitrógeno , FosfinasRESUMEN
The Pd0/Cu1 catalyzed cross-coupling of terminal alkynes onto peptide nucleic acid monomers or submonomers bearing iodinated nucleobases has been utilized as a route to base-modified oligomers. Both 5-iodouracil and 5-iodocytosine derivatives undergo the cross-coupling to give the expected products in moderate to good yields. However, depending on the particular substrates and reaction conditions, the cross-coupling may be followed by a ring closing reaction to give the fluorescent furano- and pyrrolo-fused uracil and cytosine derivatives, respectively.
Asunto(s)
Citosina/análogos & derivados , Ácidos Nucleicos de Péptidos/química , Uracilo/análogos & derivados , Sitios de Unión , Reactivos de Enlaces Cruzados , Citosina/química , Indicadores y Reactivos , Cinética , Estructura Molecular , Uracilo/químicaRESUMEN
A new scheme for the synthesis of peptide nucleic acid (PNA) is described. First, a resin-bound amino acid is alkylated under Fukuyama-Mitsunobu conditions. A nucleobase is then incorporated via an acid fluoride. Subsequently, oligomerization may be achieved by deprotection, coupling of another amino acid, and repetition of the cycle. Each step of the submonomer synthesis has been optimized to provide essentially quantitative yield. [reaction: see text]