A-Methylphenacyl esters

The supports 9 and 10, which were synthesized starting from cross-linked chloro-methylpolystyrene, contain an acid-labile benzyl ester bond (bond a) and a photo-labile o-nitrobenzyl or a-methylphenacyl ester bond (bond b). The former is stable to photolysis and the latter are stable to acidolysis the 4-oxymethylphenylacetyl group serves as the spacer X (Scheme 2) and this permits basic or nucleophilic cleavage. 

This group was also developed by Sheehan and Umezawa as an alternative to the 4-meth-oxyphenacyl group, and both have comparable activityJ The deprotection of dipeptide a-methylphenacyl esters proceeded in higher yield than with the corresponding 4-methoxy-phenacyl esters. In the case of the a-methylphenacyl ester, dioxane was shown to be the preferred solvent for photolysis. The procedures for preparation and photolysis of the a-methylphenacyl ester are otherwise identical to those for the 4-methoxyphenacyl ester. 

Recently, on-resin mass spectrometry (MS) via the MALDI (matrix-assisted laser desorption/ionization) technique has been developed. This method can be used as a semi-on-line monitoring technique during SPPS (141). An especially elegant approach for on-resin MS is to use the photolabile a-methylphenacyl ester linker (Table 5, Q -bromophenacyl entry), which is cleaved directly upon laser photolysis and MALDI ionization (142,143). 

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