Combinatorial discovery of two-photon photoremovable protecting groups.

Pirrung, Michael C; Pieper, Wolfgang H; Kaliappan, Krishna P; Dhananjeyan, Mugunthu R · Proc Natl Acad Sci U S A · 2003

basic_science · Level V

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Abstract

A design principle for a two-photon photochemically removable protecting group based on sequential one-photon processes has been established. The expected performance of such groups in spatially directed photoactivation/photodeprotection has been shown by a kinetic analysis. One particular molecular class fitting into this design, the nitrobenzyl ethers of o-hydroxycinnamates, has been presented. An initial demonstration of two-photon deprotection of one such group prompted further optimization with respect to photochemical deprotection rate. This was accomplished by the preparation and screening of a 135-member indexed combinatorial library. Optimum performance for lambda >350 nm deprotection in organic solvent was found with 4,5-dialkoxy and -cyano substitution in the nitrobenzyl group and 4-methoxy substitution in the cinnamate.

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