Pyridyl and N,N-dimethylanilyltrifluoromethylketones forming stable gem-diols

Salvador, R. L.; Saucier, M.

doi:10.1016/s0040-4020(01)90870-1

Cited by 23 publications

(7 citation statements)

References 10 publications

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“…[44] The relatively low yields probably reflect some degree of conversion into 1,1,1,w,w,w-hexafluorodiketones, whereas the choice of trifluoroacyl donor seemingly did not affect the yield. Trifluoromethyl ketone formation by reaction of magnesium bromide trifluoroacetate, [45] ethyl trifluoroacetate, [46] or N,N-dimethyl trifluoroacetamide [47] with aromatic Grignard reagents is known. Using the same trifluoroacetylation-decarboxylation method, 1,1,1-trifluoro-4-(4-methylphenyl)butan-2-one (10) was prepared from 3-(4-methylphenyl)propanoic acid (30); however, the yield was moderate (30 %), despite the lack of other reactive functional groups (Scheme 4).…”

Section: Chemistrymentioning

confidence: 99%

“…The low yields prompted us to look for alternative reaction conditions. Trifluoromethyl ketone formation by reaction of magnesium bromide trifluoroacetate, [45] ethyl trifluoroacetate, [46] or N,N-dimethyl trifluoroacetamide [47] with aromatic Grignard reagents is known. Furthermore, the Weinreb amide of trifluoroacetic acid (N-methoxy-N-methyltrifluoroacetamide) has been used as an electrophilic trifluoromethyl ketone donor by reaction with lithioaryls generated either by direct deprotonation, [24c, 48] via halogen-lithium exchange, [24c, 49] or by reaction with aromatic Grignard reagents.…”

Section: Chemistrymentioning

confidence: 99%

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The Effect of Various Zinc Binding Groups on Inhibition of Histone Deacetylases 1–11

et al. 2013

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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 in 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 Zn(2+) -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 class I and class IIb HDAC inhibitors.

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Section: Chemistrymentioning

confidence: 99%

Section: Chemistrymentioning

confidence: 99%

The Effect of Various Zinc Binding Groups on Inhibition of Histone Deacetylases 1–11

et al. 2013

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“…The hydration of fluoroketones is well recognized (Salvador and Saucier, 1971;Guthrie, 1975;Scott and Zuman, 1976;Ritchie, 1984;Chen et al, 1986), and kinetic studies have shown that the rate of their hydration can affect inhibitor potency (Allen and Ables, 1989;Stein et al, 1987). Unfortunately, the direct measurement of the equilibrium hydration constants for compounds 1-3 in Table 1 is not possible because of their limited water solubility and poor signal-to-noise ratios in dilute solutions.…”

Section: Correlation Of K Hyd With Esterase Inhibitionmentioning

confidence: 99%

A novel geminal diol as a highly specific and stable in vivo inhibitor of insect juvenile hormone esterase

Roe

Anspaugh

Venkatesh

et al. 1997

Arch. Insect Biochem. Physiol.

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“…Materials Preparation: The following were prepared by literature methods: p ‐nitrophenyl picolinate ( 1a ),23 phenyl (2‐pyridyl)phosphonate ( 2 ),24 2‐pyridyl trifluoromethyl ketone hydrate ( 3 ),25 2‐formyl‐1‐methylbenzimidazole26 and ( R , S )‐1‐(2‐aminophenyl)ethanol and ( R , S )‐(2‐aminophenyl)(phenyl)methanol 27…”

Section: Methodsmentioning

confidence: 99%

“…With a strongly coordinating substrate, pyridyl‐CO 2 R, addition of M–OH to the bound substrate is rate‐limiting (Figure 2). 13 pro ‐TSAs 2 14 and 3 15 were thus selected to simulate the TS of metal‐mediated hydrolysis. Here we report the first examples of the elicitation of metal complex catalysts by dynamic templating with transition state analogs.…”

Section: Introductionmentioning

confidence: 99%

Evolution of Metal Complex‐Catalysts by Dynamic Templating with Transition State Analogs

2010

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The elicitation of hydrolytic catalysts from a dynamic library of imine‐zinc(II) complexes (and their precursor aldehydes and amines) via templating with pro‐transition state analogs (pro‐TSA) is described. pro‐TSA (2‐pyridyl)phosphonate 2 amplifies a benzimidazole‐derived complex at the expense of an imidazole analogue; the amplified complex is also more active for the hydrolysis of the pyridyl ester 1a. Employing pro‐TSA pyridyl hydrate 3 with libraries of Zn complexes of imines having nucleophilic side chains also perturbs the library in favor of imine‐Zn complexes which prove to be the more active hydrolytic agents and catalysts. The catalytichydrolyses exhibit both saturation kinetics and inhibition by the pro‐TSA. This process for catalyst evolution is operationally simple, amenable to high throughput screening, potentially applicable to a wide variety of catalytic reactions and thus could offer a practical alternative to catalytic antibodies and imprinted polymers.

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Pyridyl and N,N-dimethylanilyltrifluoromethylketones forming stable gem-diols

Cited by 23 publications

References 10 publications

The Effect of Various Zinc Binding Groups on Inhibition of Histone Deacetylases 1–11

The Effect of Various Zinc Binding Groups on Inhibition of Histone Deacetylases 1–11

A novel geminal diol as a highly specific and stable in vivo inhibitor of insect juvenile hormone esterase

Evolution of Metal Complex‐Catalysts by Dynamic Templating with Transition State Analogs

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