A general synthetic route for the preparation of the first analogue of a new series of sugar-modified C-nucleoside phosphonates is detailed. Such derivative contains a four-carbon l-threose sugar moiety substituted with a phosphonomethoxy group at the 3′-position and pyrrolo[2,1-f][1,2,4]triazin-4-amine as nucleobase. A C-nucleoside was initially prepared by coupling a benzyl protected l-threono-1,4-lactone intermediate with the corresponding aglycon moiety. The choice of a tert-butyldiphenylsilyl group was found to be crucial to achieve the regioselective protection of the hydroxyl group at the 3′-position. Moreover, it allowed to smoothly perform further synthetic manipulations, including the introduction of a benzyl protected phosphonate synthon under basic conditions, which eventually led to the desired compound after final deprotection.
Synthesis of a Threosyl-C-nucleoside Phosphonate
Groaz E.;
2019
Abstract
A general synthetic route for the preparation of the first analogue of a new series of sugar-modified C-nucleoside phosphonates is detailed. Such derivative contains a four-carbon l-threose sugar moiety substituted with a phosphonomethoxy group at the 3′-position and pyrrolo[2,1-f][1,2,4]triazin-4-amine as nucleobase. A C-nucleoside was initially prepared by coupling a benzyl protected l-threono-1,4-lactone intermediate with the corresponding aglycon moiety. The choice of a tert-butyldiphenylsilyl group was found to be crucial to achieve the regioselective protection of the hydroxyl group at the 3′-position. Moreover, it allowed to smoothly perform further synthetic manipulations, including the introduction of a benzyl protected phosphonate synthon under basic conditions, which eventually led to the desired compound after final deprotection.
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