Photolabile protecting group

A photolabile protecting group (PPG; also known as: photoremovable, photosensitive, or photocleavable protecting group) is a chemical modification to a molecule that can be removed with light. PPGs enable high degrees of chemoselectivity as they allow researchers to control spatial, temporal and concentration variables with light. Control of these variables is valuable as it enables multiple PPG applications, including orthogonality in systems with multiple protecting groups. As the removal of a PPG does not require chemical reagents, the photocleavage of a PPG is often referred to as "traceless reagent processes", and is often used in biological model systems and multistep organic syntheses. Since their introduction in 1962, numerous PPGs have been developed and utilized in a variety of wide-ranging applications from protein science to photoresists. Due to the large number of reported protecting groups, PPGs are often categorized by their major functional group(s); three of the most common classifications are detailed below.

Historical introduction

The first reported use of a PPG in the scientific literature was by Barltrop and Schofield, who in 1962 used 253.7 nm light to release glycine from N-benzylglycine. Following this initial report, the field rapidly expanded throughout the 1970s as Kaplan and Epstein studied PPGs in a variety of biochemical systems. During this time, a series of standards for evaluating PPG performance was compiled. An abbreviated list of these standards, which are commonly called the Lester rules, or Sheehan criteria are summarized below:

In biological systems, the protected substrate, as well as the photoproducts should be highly soluble in water; in synthesis, this requirement is not as strict

The protected substrate, as well as the photoproducts should be stable in the photolysis environment

Separation of the PPG should exhibit a quantum yield greater than 0.10

Separation of the PPG should occur through a primary photochemical process

The chromophore should absorb incident light with reasonable absorptivity

The excitation wavelength of light should be greater than 300 nm

The media and photoproducts should not absorb the incident light

A general, high-yield synthetic procedure should exist for attaching the PPG to an unprotected substrate

The protected substrate and the photoproducts should be easily separated

Main classifications

Nitrobenzyl-based PPGs

Norrish Type II mechanism

Nitrobenzyl-based PPGs are often considered the most commonly used PPGs.