Combinatorial Discovery of Two-Photon Photoremovable Protecting Groups

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 100; no. 22; pp. 12548 - 12553
• Main Authors: Pirrung, Michael C., Pieper, Wolfgang H., Kaliappan, Krishna P., Dhananjeyan, Mugunthu R.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 28.10.2003; National Acad Sciences
• Subjects: Acetates; Alcohols; Atoms & subatomic particles; Chemistry; Cinnamates - chemistry; Cinnamates - radiation effects; Combinatorial Chemistry Techniques - methods; Irradiation; Kinetics; Libraries; Light; Materials; Models, Molecular; Nitrobenzenes - chemistry; Nitrobenzenes - radiation effects; Phosphoranes; Photochemistry - methods; Photons; Physical Sciences; Solvents; Wavelengths
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2131115100

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 λ > 350 nm deprotection in organic solvent was found with 4,5-dialkoxy and α-cyano substitution in the nitrobenzyl group and 4-methoxy substitution in the cinnamate.