Synthesis of 5'-functionalized nucleosides: S-Adenosylhomocysteine analogues with the carbon-5' and sulfur atoms replaced by a vinyl or halovinyl unit |
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Authors: | Wnuk Stanislaw F Sacasa Pablo R Lewandowska Elzbieta Andrei Daniela Cai Sumin Borchardt Ronald T |
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Institution: | Department of Chemistry and Biochemistry, Florida International University, Miami, FL 33199, USA. wnuk@fiu.edu |
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Abstract: | Adenosine and uridine analogues functionalized with alkenyl or fluoroalkenyl chain at C5' were prepared employing cross-metathesis, Negishi couplings, and Wittig reactions. Metathesis of the protected 5'-deoxy-5'-methyleneadenosine or uridine analogues with six-carbon amino acids (homoallylglycines) in the presence of Grubbs catalysts gave nucleoside analogues with the C5'-C6' double bond. Alternatively, the Pd-catalyzed cross-coupling between the protected 5'-deoxy-5'-(iodomethylene) nucleosides and suitable alkylzinc bromides also provided analogues with alkenyl unit. Stereoselective Pd-catalyzed monoalkylation of 5'-(bromofluoromethylene)-5'-deoxyadenosine with alkylzinc bromides afforded adenosylhomocysteine analogues with a 6'-(fluoro)vinyl motif. The vinylic adenine nucleosides produced time-dependent inactivation of the S-adenosyl-l-homocysteine hydrolases. |
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