Synthesis of 5′-functionalized nucleosides: S-Adenosylhomocysteine analogues with the carbon-5′ and sulfur atoms replaced by a vinyl or halovinyl unit

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.

Synthesis of carbohydrate-derived (Z)-vinyl halides and silanes: Samarium-promoted stereoselective 1,2-elimination on sugar-derived α-halomethylcarbinol acetates

“…Accordingly, these derivatives have been used as intermediates in the preparation of natural products, 2 Cglycosides, 3 polyols 4 and nucleosides. 5 Despite halovinyl sugars have proven to be extremely effective tools for the elongation of the sugar chain and the preparation of very diverse carbohydrate derivatives, this topic has not been extensively investigated. This may be due to the limited access to these intermediates in enantiopure form.…”