Histone deacetylase inhibitors synthesis

Bouchain G, Delorme D. (2003) Novel hydrozmate and anihde derivatives as potent histone deacetylase inhibitors Synthesis and antiproliferative evaluation. CurrMed Chem 10 2359-2372. 

Ting Y, Taori K, Kim H, Hong, Luesch H. (2008) Total synthesis and molecular target of largazole, a histone deacetylase inhibitor. J Am Chem Soc 130 8455-8459. 

Yurek-George A, Habens F, BrimmeU M, Packham G Ganesan A. (2004) Total synthesis of spirnchostatin A, a potent histone deacetylase inhibitor. 

Design and synthesis of a potent histone deacetylase inhibitor. Journal of Medicinal Chemistry, 50, 2003-2006. 

Andrianov, V., Gaihte, V., Lola, D., Loza, E., Semenikhina, V., Kalvinsh, L, Finn, P., Petersen, K.D., Ritchie, J.W., Khan, N., Tumber, A., Collins, L.S., Vadlamudi, S.M., Bjorkhng, F. and Sehested, M. (2008) Novel amide derivatives as inhibitors of histone deacetylase Design, synthesis and SAR. European Journal of Medicinal Chemistry.. ... 

Lavoie, R., Bouchain, G., Frechette, S., Woo, S.H., Khalil, E.A., Leit, S. et al. (2001) Design and synthesis of a novel class of histone deacetylase inhibitors. Bioorganic el Medicinal Chemistry Letters, 11, 2847-2850. 

Mai, A., Massa, S., Pezzi, R., Simeoni, S., Rotili, D., Nebbioso, A. etal. (2005) Class 11 (lla)-selective histone deacetylase inhibitors. 1. Synthesis and biological evaluation of novel (aryloxopropenyl) pyrrolyl hydroxyamides. Journal of Medicinal Chemistry, 48, 3344-3353. 

Andrews, D.M., Gibson, K.M., Graham, M.A., Matusiak, Z.S., Roberts, C.A., Stokes, F.S.F. et al. (2008) Design and campaign synthesis of pyridine-based histone deacetylase inhibitors. Bioorganic ej Medicinal Chemistry Letters, 18, 2525-2529. 

Suzuki, T., Nagano, Y, Kouketsu, A., Matsuura, A., Maruyama, S., Kurotaki, M. et al. (2005) Novel Inhibitors of human histone deacetylases design, synthesis, enzyme inhibition, and cancer cell growth inhibition of SAHA-based non-hydroxamates. Journal of Medicinal Chemistry, 48, 1019—1032. 

Sternson SM, Wong JC, Grozinger CM, Schreiber SL, Synthesis of 7200 small molecules based on a substructural analysis of the histone deacetylase inhibitors trichostatin and trapoxin, Org. Lett., 3 4239-4242, 2001. 

Montero A et al (2009) Design, synthesis, biological evaluation, and structural characterization of potent histone deacetylase inhibitors based on cyclic alpha/beta-tetrapeptide architectures. J Am Chem Soc 131(8) 3033—3041... 

Andrews DM, Gibson KM, Graham MA, et al. Design and campaign synthesis of pyridine-based histone-deacetylase inhibitors. Bioorg Med Chem Lett 2008 18 2525-2529. 

An aldehyde-aldehyde coupling was also the key transformation in the synthesis of the histone deacetylase inhibitor trichostatin A (74), developed by Duan and Wang 79). Reaction of p-nitrobenzaldehyde (75) and propionaldehyde (60) catalyzed by (5)-12 gave the rather unstable enantiopure 76, which was used directly for the subsequent steps towards trichostatin A (74). Notably, the chiral secondary alcohol group is oxidized later on in the sequence. Similar to some of the examples already depicted above, the organocatalytic introduction of the targeted stereogenic center is carried out very early in the multi-step sequence (Scheme 18) (79). 

FIGURE 2.11 The strategy followed in the late stages of the total synthesis of spimchostatin A, a histone deacetylase inhibitor. Cyclic depsipeptides such as these can be assembled in modular fashion, and readily lend themselves to analog preparation hy variation of the building blocks. 

SCHEME 6.9 Synthesis of histone deacetylase inhibitors based on the structure of trichostatin A. 

Vickerstaff, E., Ladlow, M., Ley, S.V., and Warrington. B., FuUy automated multi-step solution phase synthesis using polymer-supported reagents preparation of histone deacetylase inhibitors, Org. Bio-mol Chem., 1, 2419, 2003. 

Marcaurelle LA, Comer E, Dandapani S et al (2010) An Aldol-Based Build/Couple/Pair Strategy for the Synthesis of Medium- and Large-Sized Rings Discovery of Macrocyclic Histone Deacetylase Inhibitors. J Am Chem Soc 132 16962-16976... 

A related tandem safety-catch/cyclo-release approach was used by Silverman and colleagues in the solid-phase synthesis of the cyclic peptide histone deacetylase inhibitor, microsporin A 319, extracted from the marine-derived fungus Microsportm ef. gypseum Resin-bound peptide 316... 

Gu W, Cueto M, Jensen PR, Fenical W, Silverman RB. Microsporins A and B new histone deacetylase inhibitors from the marine-derived fungus Microsporum cf. Gypseum and the solid-phase synthesis of microsporin A. Tetrahedron 2007 63 6535-6541. 

The single recently published application of the amide form was in the synthesis of the histone deacetylase inhibitor vorinostat (1691 (Figure 6.52). Phosphonium salt 166 was prepared by the reaction of triphenylphosphine with chloro[l- C]acetanilide, itself prepared via chloro [l- " C]acetyl chloride. Olefination of aldehyde 167 with the yhde produced from 166 furnished the a,/3-unsaturated amide 168 in 85% yield °. The tributylphosphonium analog was employed as a starting material for the synthesis of [ " C]GV 1550526, a glutamate co-agonist . 

Chen, P.C., Patil, V., Guerrant, W Green, P. and Oyelere, A.K. (2008) Synthesis and structure-activity relationship of histone deacetylase (HDAC) inhibitors with triazole-linked... 

Itoh Y et al (2007) Design, synthesis, structure-selectivity relationship, and effect on human cancer cells of a novel series of histone deacetylase 6-selective inhibitors. J Med Chem 50(22) 5425-5438... 

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