- Thioesters as Acyl Donors in Biocatalytic Friedel-Crafts-type Acylation Catalyzed by Acyltransferase from Pseudomonas Protegens
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Functionalization of aromatic compounds by acylation has considerable significance in synthetic organic chemistry. As an alternative to chemical Friedel-Crafts acylation, the C-acyltransferase from Pseudomonas protegens has been found to catalyze C?C bond formation with non-natural resorcinol substrates. Extending the scope of acyl donors, it is now shown that the enzyme is also able to catalyze C?S bond cleavage prior to C?C bond formation, thus aliphatic and aromatic thioesters can be used as acyl donors. It is worth to mention that this reaction can be performed in aqueous buffer. Identifying ethyl thioacetate as the most suitable acetyl donor, the products were obtained with up to >99 % conversion and up to 88 % isolated yield without using additional base additives; this represents a significant advancement to prior protocols.
- ??d?o-Dobrowolska, Anna,Schmidt, Nina G.,Kroutil, Wolfgang
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p. 1064 - 1068
(2019/01/14)
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- Biocatalytic Friedel–Crafts Acylation and Fries Reaction
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The Friedel–Crafts acylation is commonly used for the synthesis of aryl ketones, and a biocatalytic version, which may benefit from the chemo- and regioselectivity of enzymes, has not yet been introduced. Described here is a bacterial acyltransferase which can catalyze Friedel–Crafts C-acylation of phenolic substrates in buffer without the need of CoA-activated reagents. Conversions reach up to >99 %, and various C- or O-acyl donors, such as DAPG or isopropenyl acetate, are accepted by this enzyme. Furthermore the enzyme enables a Fries rearrangement-like reaction of resorcinol derivatives. These findings open an avenue for the development of alternative and selective C?C bond formation methods.
- Schmidt, Nina G.,Pavkov-Keller, Tea,Richter, Nina,Wiltschi, Birgit,Gruber, Karl,Kroutil, Wolfgang
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supporting information
p. 7615 - 7619
(2017/06/13)
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- Discovery and SAR study of hydroxyacetophenone derivatives as potent, non-steroidal farnesoid X receptor (FXR) antagonists
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Compound 1 (IC50 = 35.2 ± 7.2 μM), a moderate FXR antagonist was discovered via high-throughput screening. Structure-activity relationship studies indicated that the shape and the lipophilicity of the substituents of the aromatic ring affect the activity dramatically, increasing the shape and the lipophilicity of the substituents of the aromatic ring enhances the potency of FXR antagonists. Especially, when the OH at C2 position of the aromatic ring was replaced by the OBn substituent (analog 2b), its activity could be improved to IC50 = 1.1 ± 0.1 μM. Besides, the length of the linker and the tetrazole structure are essential for retaining the activity.
- Liu, Peng,Xu, Xing,Chen, Lili,Ma, Lei,Shen, Xu,Hu, Lihong
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p. 1596 - 1607
(2014/03/21)
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- Leukotriene B4 Receptor Antagonists: The LY255283 Series of Hydroxyacetophenones
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A series of hydroxyacetophenones was prepared for evaluation as leukotriene B4 (LTB4) receptor antagonists, culminating in 1-oxy>phenyl>ethanone (compound 35, LY255283).Using an assay for inhibition of specific LTB4 binding to human PMN, we found that substitution of a nonpolar substituent in the 5-position was required for activity.Best activity was realized with hydrogen in the 3-position, hydroxyl in the 2-position, short chain alkyl ketone in the 1-position, and a six- or eight-carbon chain linking the oxygen in the 4-position with an unsaturated terminal function.Compound 35, having an IC50 of 87 nM in the binding assay, was chosen for further preclinical evaluation.
- Herron, David K.,Goodson, Theodore,Bollinger, Nancy G.,Swanson-Bean, Dorothy,Wright, Ian G.,et al.
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p. 1818 - 1828
(2007/10/02)
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- ANTI-INFLAMMATORY AGENTS
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This invention provides benzene derivatives, pharmaceutical formulations of those derivatives, and a method of using the derivatives for the treatment of inflammation in mammals.
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- Antifungal Activity of 2,4-Dihydroxyacylophenones and Related Compounds
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The antifungal activity of 2,4-dihydroxyacylophenones and related compounds against Trichophyton spp. and other fungi were investigated to determine their structure-activity relationships.The activity of these compounds was found to be closely related to the length of the acyl and alkyl substituents attached to the 1,3-dihydroxybenzene moiety.In addition, differences in activity were observed depending on the position of the alkyl substituents and on the number of substituents attached to the 1,3-dihydroxybenzene moiety.Some compounds tested showed potent antifungal activity against Trichophyton spp. and other fungi that was more active than amphotericin B.
- Mizobuchi, Shigeyuki,Sato, Yuko
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p. 1327 - 1334
(2007/10/02)
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