Azumamide

Azumamide E is a cyclotetrapeptide natural product isolated from marine sponge Mycale izuensis. Like most cyclopeptide HDAC inhibitors, these compounds contain D-a-amino acids (D-Phe, D-Tyr, D-Ala, D-Val) which relieve ring strain (Fig. 7). However, they are unique from other natural cyclopeptide HDAC inhibitors with a retroenantio arrangement. 

Fig. 7. Chemical structure of azumamide A-E and activity against the crude enzyme extract from K562 cells. ...

Nakao Y, Yoshida S, Matsunaga S, Shindoh N, Terada Y, Nagai K, Yamashita JK, Ganesan A, van Soest RWM, Fusetani N. (2006) Azumamides A-E Histone deacetylase inhibitory cyclic tetrapeptides from the marine spong Mycale izuensis. Angew Chem Int Ed 45 7553-7557. 

Maulucci, N., Chini, M.G., Di Micco, S., Izzo, I., Cafaro, E., Russo, A. et al. (2007) Molecular insights into azumamide E histone deacetylases inhibitory activity Journal of the American Chemical Society, 129, 3007-3012. 

Nakao, Y, Yoshida, S., Matsunaga, S., Shindoh, N., Terada, Y, Nagai, K et al. (2006) Azumamides A-E histone deacetylase inhibitory cydic tetrapeptides from the marine sponge. Mycale izuensis Angewandte Chemie (International Edition in En ish), 45, 7553-7557. 

Brown s crotylboration protocol was used effectively in the synthesis of azu-mamide A 28. Azumamides are unusual cyclic peptides that show potent inhibitory activity on histone deacetylase enzymes. A highly diastereo- and enan-tioselective (dr >99% 98% ee) crotylation of 3-benzyloxypropanal with the chiral reagent ( >crotyl-1Ipc2borane (l19E) afforded the homoallylic alcohol 29. Subsequent reductive ozonolysis and K2CO3-mediated hydrolysis of the acetate furnished the diol 3016 (Scheme 3.1m). 

The azumamides A-E are cydic tetrapeptides isolated from the Japanese spedes Mycale izumsis and have the diaraderistic of possessing only a-amino adds in configuration D assodated with an imusual P-amino add 3-amino-2-methyl-5-nonendioic acid, 9-amide (amnaa). Azumamides are the first examples of inhibitors of histone deacetylase (HDAC) isolated from marine invertebrates, with IC50 values ranging from 0.045 pM for azu-mamide A to 1.3 pM for azumamide D (Nakao et al., 2006). 

Azumamides A-E histone deacetylase inhibitory cyclic tetrapeptides from the marine sponge Mycale izuensis. Angew. Chem. Int. Ed., 45, 7553-7557. 

The Azumamide Natural Products with a Carhoj lic Acid Warhead... 

The azumamides are a family of natural product HDAC inhibitors isolated from the marine sponge Mycale izuensis (Figure 4.19). Interestingly, the... 

Scheme 4.5 Synthesis of the azumamide p-amino acid via stereoselective imino...

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