Isostere-based design of 8-azacoumarin-type photolabile protecting groups: a hydrophilicity-increasing strategy for coumarin-4-ylmethyls.

Described is the development of 8-azacoumarin-4-ylmethyl groups as aqueous photolabile protecting groups. A key feature of the strategy is the isosteric replacement of the C7-C8 enol double bond of the Bhc derivative with an amide bond, resulting in conversion of the chromophore from coumarin to 8-azacoumarin. This strategy makes dramatically enhanced water solubility and facile photocleavage possible.