7530-92-9Relevant articles and documents
Process Development and Scale-up Total Synthesis of Largazole, a Potent Class i Histone Deacetylase Inhibitor
Chen, Qi-Yin,Chaturvedi, Pravin R.,Luesch, Hendrik
, p. 190 - 199 (2018/02/23)
Herein we describe the research and development of the process for the scale-up total synthesis of largazole, a potent class I selective histone deacetylase (HDAC) inhibitor, a potential anticancer agent and also useful for the treatment of other disorders where transcriptional reprogramming might be beneficial. The synthetic route and conditions for each fragment and final product were modified and optimized to make them suitable for larger-scale synthesis. With the process we developed, hundreds of grams of each fragment and decagrams of final product largazole were synthesized in good to excellent yields. The final target largazole was obtained in 21% overall yield over eight steps based on the longest sequence with over 95% HPLC purity.
Thioacids mediated selective and mild N-acylation of amines
Mali, Sachitanand M.,Bhaisare, Rupal D.,Gopi, Hosahudya N.
, p. 5550 - 5555 (2013/07/25)
N-Acylated amines are ubiquitous in nature. Selective N-acylation at neutral conditions remains a key area of interest. Here we are reporting the copper sulfate-mediated highly selective, mild, and rapid N-acylation of various aliphatic and aromatic amines using thioacids in methanol at neutral conditions. All N-acylated products of primary and secondary amines were isolated in good to excellent yields. This method is found to be highly selective for the amines and not sensitive to other functional groups such as phenols, alcohols, and thiols. The simple workup, high yields, and high selectivity of this reaction can be an attractive alternative to those of the existing acyl halide- and acid anhydride-mediated N-acylation reactions.
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.
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.
Synthesis and biological activity of largazole and derivatives
Seiser, Tobias,Kamena, Faustin,Cramer, Nicolai
supporting information; experimental part, p. 6483 - 6485 (2009/03/11)
A modular synthesis of the marine natural product largazole and related synthetic analogues is described. Largazole was prepared in 19% overall yield through a synthetic route with a longest linear sequence of nine steps. Activity tests showed the necessity of the thiobutenyl moiety for antiproliferative activity. (Chemical Equation Presented).
A concise total synthesis of largazole, solution structure, and some preliminary structure activity relationships
Nasveschuk, Christopher G.,Ungermannova, Dana,Liu, Xuedong,Phillips, Andrew J.
supporting information; experimental part, p. 3595 - 3598 (2009/05/07)
(Chemical Equation Presented) A total synthesis of largazole that proceeds in 8 steps from commercial materials is reported, along with some structure-activity relationships. A combination of NMR studies and molecular modeling have also provided a preliminary picture of the conformation of largazole.
A facile synthesis of thioacids by hydrolysis of 1-(acylthio)ethaniminium chlorides
Toriyama, Masaharu,Kamijo, Haruo,Motohashi, Shigeyasu,Takido, Toshio,Itabashi, Kunio
, p. 1661 - 1665 (2007/10/03)
A facile method for the preparation of thioacids in moderate to good yields has been developed by hydrolysis of 1-(acylthio)ethaniminium chlorides under a liquid-liquid two phase system consisting of benzene and a sodium hydroxide aqueous solution at room temperature. We have achieved facile preparation of these compounds without use of toxic compounds such as hydrogen sulfide.
