180973-26-6Relevant articles and documents
Synthesis and biological characterization of the histone deacetylase inhibitor largazole and C7- modified analogues
Souto, José A.,Vaz, Esther,Lepore, Ilaria,P?ppler, Ann-Christin,Franci, Gianluigi,álvarez, Rosana,Altucci, Lucia,De Lera, ángel R.
supporting information; scheme or table, p. 4654 - 4667 (2010/10/02)
Largazole 4a and analogues with modifications at the C7 position, as well as 2,4′-bithiazole 5a, have been synthesized using an acyclic cross-metathesis of the corresponding depsipeptide structures assembled by N-C6(O) or C15(O)-N lactam formation. Similar to the parent system 4a, the series of largazole depsipeptides 4b-d, but not 2,4′-bithiazole 5a, showed a marked inhibition of recombinant HDAC1 and selectivity over HDAC4, as well as strong pro-apoptotic effects on the NB4 leukemia cell line, but they failed to induce differentiation to mature granulocytes. Functional assays of the analogues correlated with the in vitro activities, as shown by increased H3 and α-tubulin acetylation levels and p21WAF1/CIP1 up-regulation in NB4 cells. The activity of the natural product HDACi largazole 4a is not significantly altered by the presence of groups of different size (H, Et, Ph) at C7 on the dihydrothiazole ring.
Total Synthesis of the Depsipeptide FR-901375
Chen, Yanping,Gambs, Celine,Abe, Yoshito,Wentworth Jr., Paul,Janda, Kim D.
, p. 8902 - 8905 (2007/10/03)
The first total synthesis of FR-901375, a novel bicyclic depsipeptide isolated from the fermentation broth of Pseudomonas chloroaphis No. 2522, has been achieved. The synthetic approach involves 13 reaction steps and is achieved in 12% overall yield. The key points in the successful synthetic strategy are a concise asymmetric synthesis of the key building block (3R,4E)-3-hydroxy-7-mercapto-4-heptenoic acid, a mild Mitsunobu macrolactonization step, and an I2-mediated deprotection with concomitant disulfide-bridge formation.
