Alex R. Maolanon

Auzzas L.

Beumer J. H.

Bradner J. E.

Chandrasekhar S.

Christian A. Olsen

Cutter A. C.

Darkin-Rattray S. J.

Furumai R.

Haberland M.

Helle M. Stephansen

Inks E. S.

Ireland R. E.

Izzo I.

Jesper S. Villadsen

Kazantsev A. G.

Kijima M.

Lahm A.

Madsen A. S.

Marks P. A.

Maulucci N.

Minucci S.

Montero A.

Nakao Y.

Oare D. A.

Olsen C. A.

Pernille Harris

Robak M. T.

Szpilman A. M.

Tang T. P.

Taunton J.

Vickers C. J.

Wang D.

Wen S.

Wender P. A.

White C. J.

Wilson R. M.

Zimmerman H. E.

Crossref

Journal of Medicinal Chemistry

Total Synthesis and Full Histone Deacetylase Inhibitory Profiling of Azumamides A–E as Well as β2- epi-Azumamide E and β3-epi-Azumamide E

Cyclic tetrapeptide and depsipeptide natural products have proven useful as biological probes and drug candidates due to their potent activities as histone deacetylase (HDAC) inhibitors. Here, we present the syntheses of a class of cyclic tetrapeptide HDAC inhibitors, the azumamides, by a concise route in which the key step in preparation of the noncanonical disubstituted β-amino acid building block was an Ellman-type Mannich reaction. By tweaking the reaction conditions during this transformation, we gained access to the natural products as well as two epimeric homologues. Thus, the first total syntheses of azumamides B–D corroborated the originally assigned structures, and the synthetic efforts enabled the first full profiling of HDAC inhibitory properties of the entire selection of azumamides A–E. This revealed unexpected differences in the relative potencies within the class and showed that azumamides C and E are both potent inhibitors of HDAC10 and HDAC11

Villadsen, Jesper

Stephansen, Helle Marie

Maolanon, Alex

Harris, Pernille

Olsen, Christian Adam

Online Research Database In Technology

Total Synthesis and Full Histone Deacetylase Inhibitory Profiling of Azumamides A–E as Well as β2- epi-Azumamide E and β3-epi-Azumamide E

Stephansen, Helle M.

Maolanon, Alex R.

Copenhagen University Research Information System

Total Synthesis and Full Histone Deacetylase Inhibitory Profiling of Azumamides A-E as Well as beta(2)- epi-Azumamide E and beta(3)-epi-Azumamide E

http://orbit.dtu.dk/ws/files/60458297/jm4008449.pdf

Total Synthesis and Full Histone Deacetylase Inhibitory Profiling of Azumamides A–E as Well as β2- epi-Azumamide E and β3-epi-Azumamide E

Abstract

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Crossref

Online Research Database In Technology

Copenhagen University Research Information System