432514-48-2Relevant academic research and scientific papers
Tungsten-Catalyzed Transamidation of Tertiary Alkyl Amides
Feng, Fang-Fang,Liu, Xuan-Yu,Cheung, Chi Wai,Ma, Jun-An
, p. 7070 - 7079 (2021/06/30)
Transamidation has recently emerged as a straightforward and convenient means to diversify amides. However, the kinetically and thermodynamically demanding transamidation of notoriously robust, fully alkyl-substituted tertiary amides still remains a longstanding challenge. Here, we describe a method for the activation of tertiary alkyl amides to streamline transamidation using simple tungsten(VI) chloride as a catalyst and chlorotrimethylsilane as an additive. The highly electrophilic and oxophilic tungsten catalyst enables the selective scission of a C-N bond of tertiary alkyl amides to effect transamidation of a myriad of structurally and electronically diverse tertiary alkyl amides and amines. Mechanistic study implies that the synergistic effect of the catalyst and the additive could pronouncedly induce the nucleophilic acyl substitution of tertiary alkyl amide with amine to realize transamidation.
Zn2+-Chelating Motif-Tethered Short-Chain Fatty Acids as a Novel Class of Histone Deacetylase Inhibitors
Lu, Qiang,Yang, Ya-Ting,Chen, Chang-Shi,Davis, Melanie,Byrd, John C.,Etherton, Mark R.,Umar, Asad,Chen, Ching-Shih
, p. 467 - 474 (2007/10/03)
Among various classes of histone deacetylase (HDAC) inhibitors, short-chain fatty acids exhibit the least potency, with IC50 in the millimolar range. We rationalized that this weak potency was, in part, attributable to their inability to access the zinc cation in the HDAC active-site pocket, which is pivotal to the deacetylation catalysis. We thus explored the structural optimization of valproate, butyrate, phenylacetate, and phenylbutyrate by coupling them with Zn2+-chelating motifs (hydroxamic acid and o-phenylenediamine) through aromatic ω-amino acid linkers. This strategy has led to a novel class of Zn2+-chelating, motif-tethered, short-chain fatty acids that exhibited varying degrees of HDAC inhibitory potency. One hydroxamatetethered phenylbutyrate compound, N-hydroxy-4-(4-phenylbutyrylamino)benzamide (HTPB), displayed nanomolar potency in inhibiting HDAC activity. Exposure of several cancer cell lines to HTPB at the submicromolar level showed reduced cell proliferation accompanied by histone hyperacetylation and elevated p21WAF/CIP1 expression, which are hallmark features associated with intracellular HDAC inhibition.
