Photolabile linker units

Photolabile linkers are stable under a number of reaction conditions in organic synthesis, and they also allow release under neutral conditions. Photolabile linking groups for hydroxy and amino functions can be divided into three different basic entities, as shown in Fig. 13. 

For application in combinatorial synthesis, photolabile linkers must be modified to allow for attachment to the solid support, and must be further modified to adjust the cleavage step after combinatorial synthesis to the requirements of the photo-lytic removal of the target molecules from the support (modulation of photolytic cleavage kinetics). For combinatorial synthesis, only the o-nitrobenzyl-derived linkers have found wide application, while the Desyl-derived linker has been used mostly in photolithographic DNA synthesis. 

Photolabile hnker units based on the phenacyl group have also been developed. The hnker is essentially a functionalized resin since it is easily prepared by Friedel-Crafts acylation of typical polystyrene resin. Like the nitrobenzyl hnkers, cleavage from the phenacyl hnker units can be achieved by irradiating at 350 nm (Table 1.5, Entry 5). A related hnker unit is the para-methoxyphenacyl hnker and, in this case, the para-methoxy group improves the efficiency of the photolysis and, thus, cleavage times are reduced. 

LINKER STRATEGIES IN MODERN SOLID-PHASE ORGANIC SYNTHESIS 

---

More recently. Erase has also introduced the T2 triazene linker unit. The T2 linkers are most commonly used for immobilization of amines (and other nitrogenous compounds). As their T1 counterparts, the T2 linkers have also proven robust linkers for SPOS. For example, amines can be cleaved by treating with TFA (Table 1.8, Entry 1), while treatment with trimethylsilyl chloride is typically used when preparing (and cleaving) ureas (Table 1.8, Entry 2) or amides (Table 1.8, Entry 3). Alternatively, the T2 linker can also behave as a photolabile linker unit and photolytic cleavage (X, = 355 nm) by Enders et al. was used as a strategy to release amines (Table 1.8, Entry 4). ... 

Fig. 8 Photo-triggered peptide self-assembling system designed by Imperiali s group. In this molecular system, fibril-inhibitory unit was attached to the amyloidogenic unit through photolabile linker. (Adapted from [44])...

---