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. 2009 Mar 19;11(6):1301-4.
doi: 10.1021/ol900078k.

Synthesis and histone deacetylase inhibitory activity of largazole analogs: alteration of the zinc-binding domain and macrocyclic scaffold

Albert A Bowers  1 , Nathan West, Tenaya L Newkirk, Annie E Troutman-Youngman, Stuart L Schreiber, Olaf Wiest, James E Bradner, Robert M Williams
Affiliations

Synthesis and histone deacetylase inhibitory activity of largazole analogs: alteration of the zinc-binding domain and macrocyclic scaffold

Albert A Bowers et al. Org Lett. .

Abstract

Fourteen analogs of the marine natural product largazole have been prepared and assayed against histone deacetylases (HDACs) 1, 2, 3, and 6. Olefin cross-metathesis was used to efficiently access six variants of the side-chain zinc-binding domain, while adaptation of our previously reported modular synthesis allowed probing of the macrocyclic cap group.

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Figures

Figure 1
Figure 1
Selected largazole analogs and azumamide E.
Scheme 1
Scheme 1
Synthesis of largazole-azumamide Hybrid.
Scheme 2
Scheme 2
Metathesis route to largazole hybrids.
Scheme 3
Scheme 3
Synthesis of cysteine & thiazole-thiazole analogs.
Scheme 4
Scheme 4
Synthesis of thiazole to pyridine substitution.
Scheme 5
Scheme 5
Synthesis of the oxazoline-oxazole analog.
See this image and copyright information in PMC

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