Design and Synthesis of Some New α‐Phenyl Cinnamoyl Derivatives for Selective Protection of Purine Nucleosides

Abstract

Three new α‐phenylcinnamic acid derivatives [4‐methoxy‐α‐phenylcinnamic acid, α‐(4‐methoxyphenyl)‐cinnamic acid, and 4,4′‐bismethoxy‐α‐phenylcinnamic acid] were synthesized, characterized, and selectively used for protecting the exocyclic amino function of purine nucleosides (2′‐deoxyadenosine and 2′‐deoxyguanosine) via active ester generation. The acids were first activated using p‐nitrophenol, and these activated esters were used subsequently for the selective protection of amino groups. The N‐protected derivatives of 2′‐deoxyguanosine and 2′‐deoxyadenosine have been found to be sufficiently stable toward acids, thus minimizing depurination under oligodeoxyribonucleotide synthesis protocol. The ease of syntheses of N‐protected purine nucleosides, their stability under an acidic environment, and mild deprotection conditions are the key advantages of the new protecting groups.

Keywords:

• acylation
• antisense
• α‐phenylcinnamoyl
• depurination resistant

Acknowledgment

Thanks are due to Regional Sophisticated Instruments Centre, Central Drug Research Institute, Lucknow, India, for IR, mass, and NMR spectra. Authors gratefully acknowledge financial support from ISIS Pharmaceuticals USA.