Convenient Synthesis of Pyrimidine acyclo-2,2’-anhydronucleosides and their Exploitation Toward Selected N-nucleophiles

Title:Convenient Synthesis of Pyrimidine acyclo-2,2’-anhydronucleosides and their Exploitation Toward Selected N-nucleophiles

Volume: 16 Issue: 19

Author(s): Andrzej Gondela, Slawomir Boncel and Krzysztof Z. Walczak

Affiliation:

Keywords: Heterocycles, Nucleobases, Mitsunobu reaction, Oxazolidine ring opening, Nucleophilic substitution, Bioactive compounds, 2-amino-4, 5-dihydrooxazole, tetramethylsilane, chromatography, acyclic pyrimidine

Abstract: A new method of the synthesis of 2-(hydroxymethyl-2H-oxazolo[3,2-a]pyrimidin-7(3H)-ones, commonly known as pyrimidine acyclo-2,2’-anhydronucleosides, was developed. Under the Mitsunobu reaction conditions, 5-substituted 1-(3’-alkoxy-2’- hydroxypropyl)uracil derivatives underwent an intramolecular cyclization to the corresponding 2-alkoxymethyl-2,3-dihydro-7Hoxazolo[ 3,2-a]pyrimidin-7-ones. The various synthetic methods have been demonstrated in the reactions with several N-nucleophiles. Importantly from the mechanistic point of view, in the case of 6-bromo-2-(hydroxymethyl)-2H-oxazolo[3,2-a]pyrimidin-7(3H)-one treated with chiral isocyanate the inversion of configuration at the C-4’ carbon atom accompanied by the oxazolidine ring opening was observed.

Cite this article as:

Gondela Andrzej, Boncel Slawomir and Z. Walczak Krzysztof, Convenient Synthesis of Pyrimidine acyclo-2,2’-anhydronucleosides and their Exploitation Toward Selected N-nucleophiles, Current Organic Chemistry 2012; 16 (19) . https://dx.doi.org/10.2174/138527212803520209