Weinreb Derivatives and Hydroxamates

Conversion of solid-supported hydroxamates to aldehydes is a useful tool for the generation of C-terminal peptide-aldehydes. Martinez et aL firstly used LiAlH4-reduction for the cleavage of hydroxamates from solid supports and succeeded in synthesizing tripeptide aldehydes that could be obtained in about 40% yield after purification [83]. Reduction of Weinreb amides on 

The reaction of Weinreb amides to ketones can be performed cleanly using Grignard reagents in large excess. Yields of that transformation range from 16% up to 78% and no overaddition was observed as described by Armstrong et al. on Rink resin [213]. 

Taddei et al. used Sml2 to cleave N - 0 bonds in hydroxamic acids and adapted a method for the first time used in soHd phase synthesis by Abell et al. [220]. Former applications in solution phase [221] showed that Smb is a useful reagent for many transformations which avoids acidic conditions for cleavage of amides. Another example for the release of cychc substrates from hydroxamate linkers was also given by Taddei et al. [218]. 

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