Bicyclo[6.1.0]nonyne Phoshoramidites for Metal-Free Conjugation of Oligonucleotides

摘要

Phosphoramidite building blocks based on a bicyclo[6.1.0]nonyne (BCN) core, are developed and readily integrated into solid phase synthesis of oligonucleotides. Strategies are reported for the preparation of oligonucleotides containing either a 5'-conjugated or an internal BCN, and a lipophilicity comparison is made with a dibenzoannulated cyciooctyne. It is demonstrated that smooth and efficient conjugation to azido-containing functional groups takes place. The reported building blocks and strategy pave the way for the preparation of a wide variety of oligonucleotide conjugates based on readily available building blocks.