85674-68-6Relevant articles and documents
Efficient Asymmetric Biomimetic Aldol Reaction of Glycinates and Trifluoromethyl Ketones by Carbonyl Catalysis
Cao, Jing,Cheng, Aolin,Liu, Tao,Song, Guanshui,Zhang, Kun,Zhang, Liangliang,Zhao, Baoguo,Zhao, Guoqing,Zhou, Qinghai
supporting information, p. 20166 - 20172 (2021/07/20)
The direct asymmetric aldol reaction of glycinates represents an intriguing and straightforward strategy to make biologically significant chiral β-hydroxy-α-amino-acid derivatives. But it is not easy to realize the transformation due to the disruption of the reactive NH2 group of glycinates. Inspired by the enzymatic aldol reaction of glycine, we successfully developed an asymmetric aldol reaction of glycinate 5 and trifluoromethyl ketones 4 with 0.1–0.0033 mol % of chiral N-methyl pyridoxal 7 a as the catalyst, producing chiral β-trifluoromethyl-β-hydroxy-α-amino-acid esters 6 in 55–82 % yields (for the syn-diastereomers) with up to >20:1 dr and 99 % ee under very mild conditions. The reaction proceeds via a catalytic cycle similar to the enzymatic aldol reaction of glycine. Pyridoxal catalyst 7 a activates both reactants at the same time and brings them together in a specific spatial orientation, accounting for the high efficiency as well as excellent diastereo- and enantioselectivities.
Photoredox Generation of Carbon-Centered Radicals Enables the Construction of 1,1-Difluoroalkene Carbonyl Mimics
Lang, Simon B.,Wiles, Rebecca J.,Kelly, Christopher B.,Molander, Gary A.
supporting information, p. 15073 - 15077 (2017/11/20)
Described is a facile, scalable route to access functional-group-rich gem-difluoroalkenes. Using visible-light-activated catalysts in conjunction with an arsenal of carbon-radical precursors, an array of trifluoromethyl-substituted alkenes undergoes radical defluorinative alkylation. Nonstabilized primary, secondary, and tertiary radicals can be used to install functional groups in a convergent manner, which would otherwise be challenging by two-electron pathways. The process readily extends to other perfluoroalkyl-substituted alkenes. In addition, we report the development of an organotrifluoroborate reagent to expedite the synthesis of the requisite trifluoromethyl-substituted alkene starting materials.
The effect of various zinc binding groups on inhibition of histone deacetylases 1-11
Madsen, Andreas S.,Kristensen, Helle M. E.,Lanz, Gyrithe,Olsen, Christian A.
, p. 614 - 626 (2014/03/21)
Histone deacetylases (HDACs) have the ability to cleave the acetyl groups of ε-N-acetylated lysine residues in a variety of proteins. Given that human cells contain thousands of different acetylated lysine residues, HDACS may regulate a wide variety of processes including some implicated in conditions such as cancer and neurodegenerative disorders. Herein we report the synthesis and ina vitro biochemical profiling of a series of compounds, including known inhibitors as well as novel chemotypes, that incorporate putative new zinc binding domains. By evaluating the compound collection against all 11 recombinant human HDACs, we found that the trifluoromethyl ketone functionality provides potent inhibition of all four subclasses of the Zn2+- dependent HDACs. Potent inhibition was observed with two different scaffolds, demonstrating the efficiency of the trifluoromethyl ketone moiety as a zinc binding motif. Interestingly, we also identified silanediol as a zinc binding group with potential for future development of non-hydroxamate classa I and classa IIb HDAC inhibitors.
