66202-87-7Relevant academic research and scientific papers
Synthesis of pharmaceutical drugs from cardanol derived from cashew nut shell liquid
Shi, Yiping,Kamer, Paul C. J.,Cole-Hamilton, David J.
, p. 1043 - 1053 (2019/03/12)
Cardanol from cashew nut shell liquid extracted from cashew nut shells was successfully converted into various useful pharmaceutical drugs, such as norfenefrine, rac-phenylephrine, etilefrine and fenoprofene. 3-Vinylphenol, the key intermediate for the synthesis of these drugs, was synthesised from cardanol by ethenolysis to 3-non-8-enylphenol followed by isomerising ethenolysis. The metathesis reaction worked very well using DCM, but the greener solvent, 2-methyl tetrahydrofuran, also gave very similar results. Hydroxyamination of 3-vinylphenol with an iron porphyrin catalyst afforded norfenefrine in over 70% yield. Methylation and ethylation of norfenefrine afforded rac-phenylephrine and etilefrine respectively. A sequence of C-O coupling, isomerising metathesis and selective methoxycarbonylation afforded fenoprofene in good yield. A comparison of the routes described in this paper with some standard literature syntheses of 3-vinylphenol and of the drug molecules shows significant environmental advantages in terms of precursors, yields, number of steps, conditions and the use of catalysts. The Atom Economy of our processes is generally similar or significantly superior to those of the literature processes mainly because the side products produced during synthesis of 3-vinylphenol (1-octeme, 1,4-cyclohexadiene and propene) are easily separable and of commercial value, especially as they are bio-derived. The E Factor for the production of 2-vinylphenol by our process is also very low compared with those of previously reported syntheses.
Selective Methylation of Arenes: A Radical C?H Functionalization/Cross-Coupling Sequence
Serpier, Fabien,Pan, Fei,Ham, Won Seok,Jacq, Jér?me,Genicot, Christophe,Ritter, Tobias
supporting information, p. 10697 - 10701 (2018/07/31)
A selective, nonchelation-assisted methylation of arenes has been developed. The overall transformation, which combines a C?H functionalization reaction with a nickel-catalyzed cross-coupling, offers rapid access to methylated arenes with high para selectivity. The reaction is amenable to late-stage methylation of small-molecule pharmaceuticals.
Selective aryne formation via Grob fragmentation from the [2+2] cycloadducts of 3-triflyloxyarynes
Shi, Jiarong,Xu, Hai,Qiu, Dachuan,He, Jia,Li, Yang
, p. 623 - 626 (2017/05/15)
A chemoselective ring-opening protocol of the formal [2+2] cycloadducts of 3-triflyloxyarynes was developed to generate 2,3-aryne intermediate via Grob fragmentation. A variety of 1,3-di- and 1, 2, 3-trisubstituted arenes could be readily accessed through this [2+2] cycloaddition-2,3-aryne formation sequence. The regioselectivity in these transformations originates from the steric repulsion of the aliphatic chain.
Direct C-H Cyanation of Arenes via Organic Photoredox Catalysis
McManus, Joshua B.,Nicewicz, David A.
supporting information, p. 2880 - 2883 (2017/03/11)
Methods for the direct C-H functionalization of aromatic compounds are in demand for a variety of applications, including the synthesis of agrochemicals, pharmaceuticals, and materials. Herein, we disclose the construction of aromatic nitriles via direct C-H functionalization using an acridinium photoredox catalyst and trimethylsilyl cyanide under an aerobic atmosphere. The reaction proceeds at room temperature under mild conditions and has proven to be compatible with a variety of electron-donating and -withdrawing groups, halogens, and nitrogen- and oxygen-containing heterocycles, as well as aromatic-containing pharmaceutical agents.
Substrate-selective inhibition of cyclooxygenase-2: Development and evaluation of achiral profen probes
Windsor, Matthew A.,Hermanson, Daniel J.,Kingsley, Philip J.,Xu, Shu,Crews, Brenda C.,Ho, Winnie,Keenan, Catherine M.,Banerjee, Surajit,Sharkey, Keith A.,Marnett, Lawrence J.
supporting information, p. 759 - 763 (2012/10/29)
Cyclooxygenase-2 (COX-2) oxygenates arachidonic acid and the endocannabinoids 2-arachidonoylglycerol (2-AG) and arachidonoylethanolamide (AEA). We recently reported that (R)-profens selectively inhibit endocannabinoid oxygenation but not arachidonic acid oxygenation. In this work, we synthesized achiral derivatives of five profen scaffolds and evaluated them for substrate-selective inhibition using in vitro and cellular assays. The size of the substituents dictated the inhibitory strength of the analogs, with smaller substituents enabling greater potency but less selectivity. Inhibitors based on the flurbiprofen scaffold possessed the greatest potency and selectivity, with desmethylflurbiprofen (3a) exhibiting an IC50 of 0.11 μM for inhibition of 2-AG oxygenation. The crystal structure of desmethylflurbiprofen complexed to mCOX-2 demonstrated a similar binding mode to other profens. Desmethylflurbiprofen exhibited a half-life in mice comparable to that of ibuprofen. The data presented suggest that achiral profens can act as lead molecules toward in vivo probes of substrate-selective COX-2 inhibition.
(R,S)-azolides as novel substrates for lipase-catalyzed hydrolytic resolution in organic solvents
Wang, Pei-Yun,Chen, Ying-Ju,Wu, An-Chi,Lin, Yi-Sheng,Kao, Min-Fang,Chen, Jin-Ru,Ciou, Jyun-Fen,Tsai, Shau-Wei
supporting information; experimental part, p. 2333 - 2341 (2009/12/27)
Azolides, that is, N-acylazoles, as versatile acylation reagents are well characterized in the literature, in which the azole structure can not only act as a better leaving group but also make the carbonyl carbon more electrophilic and susceptible to nucleophilic attack. It is therefore desirable to combine this unique property and lipase resolution ability in the development of a new resolution process for preparing optically pure carboxylic acids. With the Candida antarctica lipase B (CALB)-catalyzed hydrolysis of (R,S)-N- profenylazoles in organic solvents as the model system, (R,S)-N-profenyl-l,2,4- triazoles instead of their corresponding ester analogues were exploited as the best substrates for preparing optically pure profens, i.e., 2-arylpropionic acids. The structure-reactivity correlations for the (R,S)-azolides in water-saturated methyl tert-butyl ether (MTBE) at 45°C coupled with a thorough kinetic analysis were further employed for elucidating the rate-limiting formation of a tetrahedral adduct without C-N bond breaking or with moderate C-N bond breaking concerted with C-O bond formation in the acylation step. The advantages of easy substrate preparation, high enzyme reactivity and enantioselectivity, and easy recovery of the product and remaining substrate by aqueous extraction demonstrate the potential of using (R,S)-azolides as novel substrates for the enzymatic resolution process.
The geminal dimethyl analogue of Flurbiprofen as a novel Aβ42 inhibitor and potential Alzheimer's disease modifying agent
Stock, Nicholas,Munoz, Benito,Wrigley, Jonathan D.J.,Shearman, Mark S.,Beher, Dirk,Peachey, James,Williamson, Toni L.,Bain, Gretchen,Chen, Weichao,Jiang, Xiaohui,St-Jacques, Rene,Prasit, Peppi
, p. 2219 - 2223 (2007/10/03)
The subtle modification of a selection of Aβ42 inhibiting non-steroidal anti-inflammatory drugs (NSAIDs), through synthesis of the geminal dimethyl analogues, was anticipated to ablate their cyclooxygenase activity whilst maintaining Aβ42 inhibition. Methylflurbiprofen 6 exhibited similar in vitro Aβ42 inhibition to its parent NSAID Flurbiprofen and was further evaluated in the Tg2576 mouse model of Alzheimer's disease and an animal model of gastro-intestinal (GI) impairment, but proved unviable for further clinical development.
An efficient synthesis of fenoprofen, an important antiinflammatory agent
Sonawane, H. R.,Nanjundiah, B. S.,Nazeruddin, G. M.
, p. 705 - 706 (2007/10/02)
A simple and practical synthesis of (+/-)-fenoprofen, a well-known non-steroidal antiinflammatory agent, from the commercially available m-phenoxybenzaldehyde has been described.
Nucleophilic substitution process
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, (2008/06/13)
Nitrophenoxy- or nitrophenylthiobenzeneacetic acid esters are prepared by reacting a nitrophenoxy- or nitrophenylthiobenzene with an alpha,alpha-disubstituted acetic acid ester in an inert solvent and in the presence of a base. The products are useful as intermediates for the synthesis of pharmaceuticals, such as fenoprofen.
Nucleophilic substitution process
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, (2008/06/13)
Nitroarylacetic acid esters are prepared by reacting a nitroaromatic compound which is devoid of halogen on the aromatic ring carrying a nitro group with an alpha,alpha-disubstituted acetic acid ester in an inert solvent and in the presence of a base so that the ester undergoes a nucleophilic substitution on an unsubstituted ring carbon of the nitroaromatic compound during which an alpha-substituent functions as a leaving group. Nitrobenzene acetic acids and their esters are useful intermediates for the synthesis of pharmaceuticals.
