6-Phenylpyrrolocytidine: An Intrinsically Fluorescent, Environmentally Responsive Nucleoside Analogue

The detailed synthetic protocols for the preparation of phosphoramidite reagents compatible with standard, automated oligonucleotide synthesis for the 2′-deoxy- and ribo-6-phenylpyrrolocyitidine are reported. Each protocol starts with the parent nucleoside and prepares the 5′-O-dimethoxytrityl-N⁴-benzoyl-5-iodocytosine derivative for the nucleobase modification chemistry. The key step is the direct formation of 6-phenylpyrrolocytosine aglycon via a sequential, one-pot Pd-catalyzed Sonogashira-type cross- coupling followed by a 5-endo-dig cyclization. Subsequent standard transformations provide the deoxy- and 2′-O-tert-butyldimethysilyl protected ribo- nucleoside phosphoramidite reagents. © 2019 by John Wiley & Sons, Inc.