Ozonization solid support

Karlsson JO, Gatenholm P (1996) Solid-supported wettable hydrogels prepared by ozone induced grafting. Polymer 37 4251 256... 

We have focused our attention on the solid phase synthesis of such compounds and described our results here. Alternative routes for the preparation of peptide aldehydes and side-chain protected peptide aldehydes in solid phase synthesis are described. Three new linkers that are stable tmder classical Fmoc or Boc strategies have been developed to obtain the peptide aldehyde from the solid support. One of these linkers was conceptualized on the basis of the Weinreb amide (49) and the other on the basis of phenolic esters (50). Both strategies required the reduction with hydrides of the peptide-linker-resin to release the peptidic aldehydic function. The use of these two different approaches was demonstrated by the synthesis of N-protected a-amino-aldehydes and peptide aldehydes, llie third approach used the ozonolysis reaction for the generation of the desired aldehyde. This concept requires a linker incorporating a double bond in the a-position of the asymmetric carbon of the C-terminal residue that will be cleaved by ozone to produce the carbonyl function. 

Silyl ethers of aliphatic alcohols are inert towards strong bases, oxidants (ozone [81], Dess-Martin periodinane [605], iodonium salts [610,611], sulfur trioxide-pyridine complex [398]), and weak acids (e.g., 1 mol/L HC02H in DCM [605]), but can be selectively cleaved by treatment with HF in pyridine or with TBAF (Table 3.32). Phenols can also be linked to insoluble supports as silyl ethers, but these are less stable than alkyl silyl ethers and can even be cleaved by treatment with acyl halides under basic reaction conditions [595], Silyl ether attachment has been successfully used for the solid-phase synthesis of oligosaccharides [600,601,612,613] and peptides [614]. 

Several references have appeared on the use of solid-phase oxidants. Solid potassium permanganate-copper sulphate mixtures oxidize secondary alcohols to ketones in high yield, and pyridinium chromate or chromic acid on silica gel are described as convenient off-the-shelf reagents for oxidation of both primary and secondary alcohols. Anhydrous chromium trioxide-celite effects similar transformations only when ether is present as co-solvent. An excellent review, with over 400 references, on supported oxidants covers the use of silver carbonate-celite, chromium trioxide-pyridine-celite, ozone-silica, chromyl chloride-silica, chromium trioxide-graphite, manganese dioxide-carbon, and potassium permanganate-molecular sieve. 

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