Peptides and their derivatives are being extensively studied and have shown to be effective in the treatment of cancer as carriers for chemotherapeutic drugs, as antibiotics, as probes for imaging and diagnosing diseases, and as new routes for drug development and design. Mild decarboxylation is a novel approach for creating new carbon-carbon bonds and can be used for the synthesis of peptides and peptidomimetics. Usually decarboxylation requires heating of up to 190 �C or the use of high powered microwaves (800 W); however, such reactions often result in low yield and decomposition of the reagents. We now report a novel method which demonstrates the use of benzotriazole for the mono-activation of 2,2-disubstituted malonic acids. The reaction resulted in decarboxylation that occurred under much milder conditions (50 �C, MW 50 W).  The monocarbonylbenzotriazolyl intermediates were then reacted with peptides in-situ forming peptidomimetics with the N-terminus residue of disubstituted carboxylic acids. These one-pot activation/decarboxylation/acylation processes retain the enantiopurity of the peptide chain due mostly to the mild reaction conditions used.

Mild decarboxylation of 2,2- disubstituted malonic acid and their reactions with peptides

246th National Meeting (2013)

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