Palladium‐Catalyzed Asymmetric Hydrogenation of α‐Acyloxy‐1‐arylethanones

Chen, Jianzhong; Liu, Delong; Butt, Nicholas; Li, Chao; Fan, Dongyang; Liu, Yangang; Zhang, Wanbin

doi:10.1002/anie.201306231

Cited by 73 publications

(23 citation statements)

References 105 publications

(11 reference statements)

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“…Still further, the catalytic system was successfully applied to α‐acyloxy, α‐morpholino and α‐semialdehyde ketones ( 3 m – 3 p ; Table 3, entries 13–16), with the α‐functional groups tolerated and high yields obtained for all of the desired products. Selective reduction of analogues of 3 m by TH is difficult, because the acyl group is prone to migration by hydrolysis 17. Indeed, there are only a few literature reports describing the TH of this class of substrates; however, the catalyst loadings are high and the yields are relatively low due to the aforementioned problem 18.…”

Section: Resultsmentioning

confidence: 99%

Versatile Iridicycle Catalysts for Highly Efficient and Chemoselective Transfer Hydrogenation of Carbonyl Compounds in Water

Talwar

Saidi

et al. 2014

Chemistry A European J

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Cyclometalated iridium complexes are shown to be highly efficient and chemoselective catalysts for the transfer hydrogenation of a wide range of carbonyl groups with formic acid in water. Examples include α-substituted ketones (α-ether, α-halo, α-hydroxy, α-amino, α-nitrile or α-ester), α-keto esters, β-keto esters and α,β-unsaturated aldehydes. The reduction was carried out at substrate/catalyst ratios of up to 50 000 at pH 4.5 and required no organic solvent. The protocol provides a practical, easy and efficient way for the synthesis of β-functionalised secondary alcohols, such as β-hydroxyethers, β-hydroxyamines and β-hydroxyhalo compounds, which are valuable intermediates in pharmaceutical, fine chemical, perfume and agrochemical synthesis.

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Section: Resultsmentioning

confidence: 99%

Versatile Iridicycle Catalysts for Highly Efficient and Chemoselective Transfer Hydrogenation of Carbonyl Compounds in Water

Talwar

Saidi

et al. 2014

Chemistry A European J

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“…Saturated Na 2 CO 3 was added, the mixture was extracted with ethyl acetate, and the extracts were washed with brine, dried over MgSO 4 , filtered, and concentrated. The residue was purified by chromatography to give target compounds 15a-d. 32,33) CDI (10.0 mmol) was dissolved in N,N-dimethylformamide (DMF) (20 mL) and to this solution a solution of the carboxylic acids 14a and d (10.0 mmol) in DMF (2 mL) was added dropwise. Subsequently, the reaction mixture was stirred at room temperature for 1 h. Then, H 2 S was bubbled gently through the reaction mixture for 2 h. Sulfuric acid (0.5 M, 40 mL) was added and the mixture was extracted with ethyl acetate.…”

Section: Methodsmentioning

confidence: 99%

Discovery and Synthesis of a Novel Series of Liver X Receptor Antagonists

Nian

Gan

Tan

et al. 2015

CHEMICAL & PHARMACEUTICAL BULLETIN

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Fourteen novel compounds were prepared and their antagonistic activities against liver X receptors (LXR) α/β were tested in vitro. Compound 26 had an IC 50 value of 6.4 µM against LXRα and an IC 50 value of 5.6 µM against LXRβ. Docking studies and the results of structure-activity relationships support the further development of this chemical series as LXRα/β antagonists.Key words liver X receptor α; liver X receptor β; antagonistic activity Nuclear receptors (NRs) are ligand-activated transcription factors that coordinate gene expression in response to the modulation of metabolism, development, proliferation, and inflammation.1,2) Liver X receptors (LXRs) belonging to the NR superfamily are activated by specific oxidized forms of cholesterol and intermediate products of the cholesterol biosynthetic pathway. 1,3,4) There are two LXR isoforms in mammals, termed LXRα and LXRβ. LXRα is abundantly expressed mainly in the liver, intestine, kidney, spleen, and adipose tissue, whereas LXRβ is more ubiquitously expressed, with particularly high levels in the developing brain. [5][6][7][8] Both isoforms share almost 80% homology of their amino acid sequences in their DNA-binding domain and ligand-binding domain. 5,7)The LXR consists of four domains: N-terminal ligandindependent activation function domain (AF-1); DNA-binding domain (DBD); hydrophobic ligand-binding domain (LBD); and C-terminal ligand-dependent transactivation sequence (AF-2).5,9,10) By forming heterodimers with retinoid X receptors (RXRs), LXRs bind to LXR response elements (LXREs) in the promoter or enhancer elements of LXR target genes. The activation of LXR-RXR heterodimers not only induces the expression of a variety of target genes (CYP7A, ABCA1, SREBP-1) that are involved in lipid and glucose metabolism, but also results in the inhibition of genes encoding inflammatory factors such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and interferon (IFN)-γ. 1,[11][12][13][14][15] In the last decade, GlaxoSmithKline and other several pharmaceutical companies have been active in developing synthetic LXR agonists (Fig. 1). T0901317 (1, Tularik) and GW3965 (2, GSK) exhibit nonselectivity for LXRα and LXRβ with high affinity.11,16-18) The first compound to enter the clinic was LXR-623 (3, Wyeth), an LXRα/β partial agonist for the potential treatment of atherosclerosis and dyslipidemia. Unfortunately, the trial was terminated due to adverse central nervous system effects.19-21) LXR antagonists reported so far include riccardin C (4, antagonist of LXRβ), naringenin (5, antagonist of LXRα), genistein (6, inhibition of LXRα or activation of LXRβ), taurine (7, antagonist of LXRα), rhein (8, antagonist of LXRα/β), SR-9238 (9, antagonist of LXRα/β), and 10 (antagonist of LXRα), among others 22-28) (Fig. 1).SR-9238 was the first selective synthetic LXR inverse agonist that displays a degree of LXRβ selectivity with an IC 50 value of 214 nM for LXRα and 43 nM for LXRβ, and this compound effectively suppressed hepatic lipogenesis, inflammation, and hepatic lipid...

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“…[6] During studies on these reactions,as mall amount of aC À Ob ond-cleavage product was observed. [6] During studies on these reactions,as mall amount of aC À Ob ond-cleavage product was observed.…”

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confidence: 99%

“…This unexpected discovery inspired the current research utilizing palladium-catalyzed hydrogenolysis for the chemo-and enantioselective CÀOb ond cleavage of ester alkyl side-chains. [6] Thes ubstrate scope of the catalytic system was explored using the optimized reaction conditions (Schemes 2a nd 3). Only the hydrogenated product 3a was obtained in TFE and DCM with full conversion (entries 1and 2), and almost no reaction occurred Scheme 1.…”

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confidence: 99%