REACTION OF N³-BENZOYL-3′,5′-O-(DI-TERT-BUTYLSILANEDIYL)URIDINE WITH HINDERED ELECTROPHILES: INTERMOLECULAR N³ To 2′-O PROTECTING GROUP TRANSFER

ABSTRACT

The compound N³-benzoyl-3′,5′-O-(di-tert-butylsilanediyl)uridine 2 was alkylated with various alkyl iodides in CH₃CN in the presence of base. Normal 2′-O-alkylated products were obtained with methyl or benzyl iodide. if hindered alkyl iodides with β-branching such as 2-ethylbutyl iodide were used as electrophiles under the same conditions, N³-alkyl-2′-O-benzoyl uridine derivatives were produced. This unexpected transformation is usually dormant with reactive alkylating agents, but expressed with sterically hindered, less reactive electrophiles. This unwanted reaction gives isomeric products whose spectra differ in only subtle ways from target compounds.

Keywords:

• Alkylation reaction
• Protecting group
• 2′-O-Alkyl ribo-nucleosides

Acknowledgments

We thank the National Science Foundation, the National Institute of General Medical Sciences, DARPA, the USAF Information Directorate Based in Rome, New York, and the New York University Technology Transfer Fund for support of this research. FAB mass spectra were obtained at the Michigan State University Mass Spectrometry Facility. ESI mass spectra were obtained at the New York University Protein Analysis Facility, Skirball Institute of Biomolecular Medicine, NYU School of Medicine.