Sulfides safety-catch linkers

Scheme 16.4 Sulfide safety-catch linker by Marshall et al.

A novel use of the Pummerer rearrangement is as a method for cleavage of sulfide safety-catch linkers. The sulfide safety-catch linker is oxidised to the sulfoxide, Pummerer rearrangement then takes place, followed by cleavage to give the desired alcohols and aldehydes. 

Scheme 16.8 Sulfide and selenide safety-catch linker by Bradley et al.

The safety catch principle for the solid-phase preparation of C-ternninal modified peptides requires the bond between the handle and the first residue to be stable to the normal conditions of SPPS. However, at the end of the synthesis, a chennical transformation of the linker substituent makes the key bond labile to nucleophiles. The 4-sulfanylphenol 44b ti and the sulfonamide 45 (Kenner) resins are two examples of safety catch resins. Thus, in the first case, which is only compatible with the Boc/Bzl strategy, once the peptide chain is elongated, treatment of the peptide-resin with hydrogen peroxide converts the sulfide into the corresponding sulfone, which makes the bond labile to nucleophiles. In the second case, N-methylation with diazomethane leads to an N-methylated peptidyl-sulfonannide-resin, from which peptides can also be cleaved by nucleophiles. 

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