Syntheses of novel 16-membered macrocyclic peptidomimetics are reported, which employ iterative peptide coupling followed by high yielding ring-closing metathesis (RCM) as the key cyclization step. The target macrocyclic compounds include examples containing a (2S)-amino-8-oxodecanoic acid (Aoda) residue as analogues of apicidin A, a known potent histone deacetylase (HDAC) inhibitor. These showed modest levels of biological activity as HDAC inhibitors.
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