- A modular and divergent approach to spirocyclic pyrrolidines
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An efficient three-step sequence to afford a valuable class of spirocyclic pyrrolidines is reported. A reductive cleavage/Horner-Wadsworth-Emmons cascade facilitates the spirocyclisation of a range of isoxazolines bearing a distal β-ketophosphonate. The spirocyclisation precursors are elaborated in a facile and modular fashion,viaa [3 + 2]-cycloaddition followed by the condensation of a phosphonate ester, introducing multiple points of divergence. The synthetic utility of this protocol has been demonstrated in the synthesis of a broad family of 1-azaspiro[4,4]nonanes and in a concise formal synthesis of the natural product (±)-cephalotaxine.
- Dixon, Darren J.,Ogura, Yusuke,Shennan, Benjamin D. A.,Smith, Peter W.
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Read Online
- Polycarboxylated compounds and compositions containing same
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Methods of selectively modifying lignin, polycarboxylated products thereof, and methods of deriving aromatic compounds therefrom. The methods comprise electrochemically oxidizing lignin using stable nitroxyl radicals to selectively oxidize primary hydroxyls on β-O-4 phenylpropanoid units to corresponding carboxylic acids while leaving the secondary hydroxyls unchanged. The oxidation results in polycarboxylated lignin in the form of a polymeric β-hydroxy acid. The polymeric β-hydroxy acid has a high loading of carboxylic acid and can be isolated in acid form, deprotonated, and/or converted to a salt. The β-hydroxy acid, anion, or salt can also be subjected to acidolysis to generate various aromatic monomers or oligomers. The initial oxidation of lignin to the polycarboxylated form renders the lignin more susceptible to acidolysis and thereby enhances the yield of aromatic monomers and oligomers obtained through acidolysis.
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Page/Page column 17-22
(2021/06/09)
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- Discovery of Conformationally Restricted Human Glutaminyl Cyclase Inhibitors as Potent Anti-Alzheimer's Agents by Structure-Based Design
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Alzheimer's disease (AD) is an incurable, progressive neurodegenerative disease whose pathogenesis cannot be defined by one single element but consists of various factors; thus, there is a call for alternative approaches to tackle the multifaceted aspects of AD. Among the potential alternative targets, we aim to focus on glutaminyl cyclase (QC), which reduces the toxic pyroform of β-amyloid in the brains of AD patients. On the basis of a putative active conformation of the prototype inhibitor 1, a series of N-substituted thiourea, urea, and α-substituted amide derivatives were developed. The structure-activity relationship analyses indicated that conformationally restrained inhibitors demonstrated much improved QC inhibition in vitro compared to nonrestricted analogues, and several selected compounds demonstrated desirable therapeutic activity in an AD mouse model. The conformational analysis of a representative inhibitor indicated that the inhibitor appeared to maintain the Z-E conformation at the active site, as it is critical for its potent activity.
- Hoang, Van-Hai,Ngo, Van T.H.,Cui, Minghua,Manh, Nguyen Van,Tran, Phuong-Thao,Ann, Jihyae,Ha, Hee-Jin,Kim, Hee,Choi, Kwanghyun,Kim, Young-Ho,Chang, Hyerim,MacAlino, Stephani Joy Y.,Lee, Jiyoun,Choi, Sun
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p. 8011 - 8027
(2019/10/11)
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- Synthesis and biological evaluation of 3-arylcoumarin derivatives as potential anti-diabetic agents
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A variety of substituted 3-arylcoumarin derivatives were synthesised through microwave radiation heating. The method has characteristics of environmental friendliness, economy, simple separation, and purification process, less by-products and high reaction yield. Those 3-arylcoumarin derivatives were screened for antioxidant, α-glucosidase inhibitory and advanced glycation end-products (AGEs) formation inhibitory. Most compounds exhibited significant antioxidant and AGEs formation inhibitory activities. Anti-diabetic activity studies showed that compounds 11 and 17 were equipotent to the standard drug glibenclamide in vivo. According to the experimental results, the target compound 35 can be used as a lead compound for the development of new anti-diabetic drugs. The whole experiment showed that anti-diabetic activity is prevalent in 3-arylcoumarins, which added a new natural skeleton to the development of anti-diabetic active drugs.
- Hu, Yuheng,Wang, Bing,Yang, Jie,Liu, Teng,Sun, Jie,Wang, Xiaojing
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- Synthesis and biological evaluation of 3-arylcoumarins as potential anti-Alzheimer's disease agents
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Alzheimer's disease, a neurodegenerative illness, has the extremely complex pathogenesis. Accumulating evidence indicates there is a close relationship between several enzymes and Alzheimer's disease. Various substituted 3-arylcoumarin derivatives were synthesised, and their in vitro activity, including cholinesterase inhibitory activity, monoamine oxidase inhibitory activity, and antioxidant activity were investigated. Most of the compounds exhibited high activity; therefore 3-arylcoumarin compounds have the potential as drug candidates for the treatment of Alzheimer's disease.
- Yang, Jie,Zhang, Pingping,Hu, Yuheng,Liu, Teng,Sun, Jie,Wang, Xiaojing
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p. 651 - 656
(2019/02/19)
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- Carboxylation of benzylic and aliphatic C-H bonds with CO2 induced by light/ketone/nickel
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A photoinduced carboxylation reaction of benzylic and aliphatic C-H bonds with CO2 is developed. Toluene derivatives capture gaseous CO2 at the benzylic position to produce phenylacetic acid derivatives when irradiated with UV light in the presence of an aromatic ketone, a nickel complex, and potassium tert-butoxide. Cyclohexane reacts with CO2 to furnish cyclohexanecar-boxylic acid under analogous reaction conditions. The present photoinduced carboxylation reaction provides a direct access from readily available hydrocarbons to the corresponding carboxylic acids with one carbon extension.
- Ishida, Naoki,Masuda, Yusuke,Imamura, Yuuya,Yamazaki, Katsushi,Murakami, Masahiro
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supporting information
p. 19611 - 19615
(2019/12/24)
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- Electrochemical Aminoxyl-Mediated Oxidation of Primary Alcohols in Lignin to Carboxylic Acids: Polymer Modification and Depolymerization
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An electrochemical process has been developed for chemoselective oxidation of primary alcohols in lignin to the corresponding carboxylic acids. The electrochemical oxidation reactions proceed under mildly basic conditions and employ 2,2,6,6-tetramethyl-1-piperidine N-oxyl (TEMPO) and 4-acetamidoO (ACT) as catalytic mediators. Lignin model compounds and related alcohols are used to conduct structure-reactivity studies that provide insights into the origin of the reaction selectivity. The method is applied to the oxidation of lignin extracted from poplar wood chips via a mild acidolysis method, and the reaction affords a novel polyelectrolyte material. Gel permeation chromatography data for the oxidized lignin shows that this material has a molecular weight and molecular weight distribution very similar to that of the extracted lignin, but notable differences are also evident. Base titration reveals a significant increase in the acid content, and the oxidized lignin has much higher water solubility relative to the extracted lignin. Treatment of the oxidized lignin under acidic conditions results in depolymerization of the material into characterized aromatic monomers in nearly 30 wt% yield.
- Rafiee, Mohammad,Alherech, Manar,Karlen, Steven D.,Stahl, Shannon S.
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supporting information
p. 15266 - 15276
(2019/10/19)
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- Design, synthesis and biological evaluation of small molecular polyphenols as entry inhibitors against H5N1
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To find novel compounds against H5N1, three series of known or novel small molecular polyphenols were synthesized and tested in vitro for anti-H5N1 activity. In addition, the preliminary structure-antiviral activity relationships were elaborated. The results showed that some small molecular polyphenols had better anti-H5N1 activity, and could serve as novel virus entry inhibitors against H 5N1, likely targeting to HA2 protein. Noticeably, compound 4a showed the strongest activity against H5N1 among these compounds, and the molecular modeling analysis also suggested that this compound might target to HA2 protein. Therefore, compound 4a is well qualified to serve as a lead compound or scaffold for the further development of H 5N1 entry inhibitor.
- Yang, Jian,Yang, Jing Xiang,Zhang, Fang,Chen, Gang,Pan, Wei,Yu, Rui,Wu, Shuwen,Tien, Po
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p. 2680 - 2684
(2014/06/09)
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- Oxidative cleavage of α-sulfonyl ketones to carboxylic acids with Ce(NH4)2(NO3)6
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Tandem oxidative cleavage of α-sulfonyl arylketones 2 with the combination of Ce(NH4)2(NO3)6 and O2 in MeCN afforded carboxylic acids 3 in moderate to good yields. The plausible reaction mechanism has
- Chang, Meng-Yang,Tsai, Chung-Yu
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supporting information
p. 5548 - 5550
(2014/12/11)
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- Novel hybrids from lamellarin D and combretastatin A 4 as cytotoxic agents
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A new series of hybrids of lamellarin D and combretastatin A 4, 1,2-diphenyl-5,6-dihydropyrrolo [2,1-a] isoquinolines, were designed as cytotoxic agents based on principles of combination in medicinal chemistry and taking the parent compounds' different anti-proliferative mechanisms into consideration. Twenty-two novel hybrids were synthesized through a convenient route, with a key step of core pyrrole formation and evaluated for their anti-proliferative activities in vitro against K-562, A-549, SMMC-7721, SGC-7901 and HCT-116 cancer cell lines. The results showed that some hybrids had good anti-proliferative activities in low IC50 ranges.
- Shen, Li,Yang, Xiaochun,Yang, Bo,He, Qiaojun,Hu, Yongzhou
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scheme or table
p. 11 - 18
(2010/03/03)
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- 2-(Trimethylsilyl)-1,3-dithiane 1-oxide as a convenient reagent for the transformation of aldehydes and ketones into homologous carboxylic acids
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Aldehydes and ketones were converted into the corresponding homologous carboxylic acids in two steps by treatment with 2-(trimethylsilyl)-1,3-dithiane 1-oxide. A modified Peterson olefination of the carbonyl compounds gave ketene thioacetal sulfoxides that were readily cleaved in acidic acetonitrile to give the required carboxylic acids. Georg Thieme Verlag Stuttgart New York.
- Krohn, Karsten,Cludius-Brandt, Stephan
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experimental part
p. 2616 - 2620
(2010/09/10)
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- Enantioselective syntheses and X-ray structures of (S)- and (R)-N-norlaudanidine: trace opium constituents
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The enantioselective synthesis of each of the enantiomers of N-norlaudanidine, a minor Papaver somniferum opium benzyltetrahydoisoquinoline alkaloid is described. This was achieved using a chiral auxiliary-mediated Bischler-Napieralski cyclization-sodium borohydride reduction strategy. The X-ray crystal structures of each of these secondary amines are reported.
- Zein, Ahmed L.,Dakhil, Otman O.,Dawe, Louise N.,Georghiou, Paris E.
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scheme or table
p. 177 - 180
(2010/03/04)
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- Enantioselective total synthesis and X-ray structures of the tetrahydroprotoberberine alkaloids (-)-(S)-tetrahydropalmatrubine and (-)-(S)-corytenchine
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Enantioselective total syntheses and X-ray structures of both (S)-tetrahydropalmatrubine (2) and (S)-corytenchine (3) are reported for the first time. They were both derived from (S)-N-norlaudanidine, a benzyltetrahydroisoquinoline that was synthesized with high (>95% ee) enantioselectivity using a chiral auxiliary-assisted Bischler-Napieralski cyclization/reduction approach.
- Zein, Ahmed L.,Dawe, Louise N.,Georghiou, Paris E.
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scheme or table
p. 1427 - 1430
(2010/10/21)
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- Oxoammonium salt/NaClO2: An expedient, catalytic system for one-pot oxidation of primary alcohols to carboxylic acids with broad substrate applicability
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A facile, green, one-pot oxidation of primary alcohols to carboxylic acids with broad substrate applicability has been developed by employing an expedient catalytic system consisting of 1-Me-AZADO+X-/NaClO 2. The Royal Society of Chemistry.
- Shibuya, Masatoshi,Sato, Takahisa,Tomizawa, Masaki,Iwabuchi, Yoshiharu
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supporting information; experimental part
p. 1739 - 1741
(2009/08/08)
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- Study of the microwave-assisted hydrolysis of nitriles and esters and the implementation of this system in rapid microwave-assisted Pd-catalyzed amination
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Microwave-assisted hydrolysis of benzonitriles and methyl benzoates has been studied using a toluene/concd aq KOH two phase system in the presence and absence of phase transfer catalyst. Conditions to allow and avoid smooth hydrolysis could be identified. Based on the latter, the first microwave protocol which allows the rapid Pd-catalyzed amination of aliphatic amines with chlorobenzenes containing sensitive functional groups has been developed.
- Van Baelen, Gitte,Maes, Bert U.W.
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p. 5604 - 5619
(2008/09/21)
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- The palladium-catalyzed preparation of condensed tetracyclic heterocycles and their application to the synthesis of rac-mangochinine
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Dihydroisoquinoline derivatives and their analogues, prepared by the Bischler-Napieralsky reaction, were converted to their indole-fused derivatives. Scope and limitations of the palladium-catalyzed reaction, proceeding through the tautomeric enamine forms of these compounds, were studied and the process was extended to the preparation of racemic mangochinine. Georg Thieme Verlag Stuttgart.
- Vincze, Zoltan,Biro, A. Beatrix,Csekei, Marton,Timari, Geza,Kotschy, Andras
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p. 1375 - 1385
(2007/10/03)
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- A collaborative effect between gold and a support induces the selective oxidation of alcohols
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Ceria nanoparticles as a support stabilize positive gold species and provide oxygen vacancies. The resulting solid exhibits an exceedingly high efficiency for the solventless aerobic oxidation of primary and secondary alcohols to carbonyl compounds (see picture). (Chemical Equation Presented)
- Abad, Alberto,Concepcion, Patricia,Corma, Avelino,Garcia, Hermenegildo
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p. 4066 - 4069
(2007/10/03)
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- Diastereoselective Synthesis of Cularine Alkaloids via Enium Ions and an Easy Entry to Isoquinolines by Aza-Wittig Electrocyclic Ring Closure
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In preliminary communications, we reported the diastereoselective synthesis of cularine and sarcocapnine via the intramolecular ring closure of nitrenium and oxenium ions, a new highly diastereoselective reductive methylation with (+)-8-phenylmenthyl chloroacetate followed by reduction with sodium borohydride, and a facile entry to the isoquinoline precursors by aza-Wittig electrocyclic ring closure. We now report the full details of the syntheses of (+)-O-demethylcularine, (+)-cularine, (+)-sarcocapnidine, (+)-sarcocapnine, and (+)-crassifoline and describe different methods of synthesis of their precursors.
- Rodrigues, J. Augusto R.,Abramovitch, Rudolph A.,De Sousa, Joana D. F.,Leiva, Genaro C.
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p. 2920 - 2928
(2007/10/03)
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- Montmorillonite clay: A novel reagent for the chemoselective hydrolysis of t-butyl esters
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A mild and highly selective hydrolysis of t-butyl esters has been achieved in high yields using montmorillonite KSF in refluxing acetonitrile. The method is compatible with a variety of protecting and functional groups such as BOC, Cbz, propargyl, allyl, benzyl, t-butyl ethers, allyl, methyl and benzyl esters present in the molecule.
- Yadav,Reddy, B. V. Subba,Rao, K. Sanjeeva,Harikishan
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p. 826 - 828
(2007/10/03)
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- Quinolones as gonadotropin releasing hormone (GnRH) antagonists: Simultaneous optimization of the C(3)-aryl and C(6)-substituents
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A series of 3-arylquinolones was prepared and evaluated for their ability to act as gonadotropin releasing hormone (GnRH) antagonists. A variety of substitution patterns of the 3-aryl substituent are described. The 3,4,5-trimethylphenyl substituent (23h) was found to be optimal. (C) 2000 Elsevier Science Ltd. All rights reserved.
- Young, Jonathan R.,Huang, Song X.,Chen, Irene,Walsh, Thomas F.,DeVita, Robert J.,Wyvratt Jr., Matthew J.,Goulet, Mark T.,Ren, Ning,Lo, Jane,Yang, Yi Tien,Yudkovitz, Joel B.,Cheng, Kang,Smith, Roy G.
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p. 1723 - 1727
(2007/10/03)
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- Method of inhibiting sweetness
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The sweetness of an ingestible product containing a sweetening sugar or sugar alcohol in large quantities can be reduced by incorporating therein a sweetness-reducing amount of at least one compound of the general formula: STR1 in which m represents 0 or 1, and when m represents 0, n represents 1, 2 or 3, and p represents 1, 2, 3 or 4, and when m represents 1, n represents 1 or 2 and p represents 0, 1, 2, 3 or 4; the substituents R, which may be the same or different, each represent a lower alkoxy group, e.g. with 1 to 5 carbon atoms, phenoxy group or a lower alkyl or trifluoromethyl group; and/or two substituents R together represent an aliphatic chain linked to the phenyl ring at two positions, either directly or via an oxa-group, e.g. an alkylenedioxy, alkenylenedioxy, alkylenoxy or alkenylenoxy group; and/or one substituent R represents a hydroxy group while at least one other substituent R represents an alkoxy group; and X+ represents a physiologically acceptable cation.
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- A NOVEL ACCESS TO 3-BENZAZEPINES AND TO 3-BENZOXEPINES VIA SRN1 RECTIONS
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A common intermediate formed by an SRN1 reaction between halohomoveratic acid and various ketone enolates leads to either benzazepines ( 5a,b,c) or to benzoxepines ( 8a,b,c) in yields ranging from 50 to 70 percent.
- Beugelmans, Rene,Ginsburg, Helene
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p. 1197 - 1203
(2007/10/02)
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- Process for preparation of alkanoic acids
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A process for preparation of substituted acetic acids having the general formula I: in which R is selected from the group consisting in one hydrogen atom and C1 -C4 -alkyl radicals, and Ar is selected from the group consisting in radicals of aromatic nature selected from the following radicals: 2-thienyl, 2-methoxy-1-naphthyl, 3,4-methylenedioxy-phenyl, and the substituted phenyls of the general formula II: STR1 where R1 is selected from the group consisting in hydrogen and C1 -C4 -alkyl groups, and R2 is selected from the group consisting in hydrogen, halogen, alkyl, alkoxy and hydroxy-groups, such process comprising the step of reacting under heat in an acid medium, in the presence of red phosphorus and catalytic quantities of iodine or hydriodic acid, an alpha carbonylated carboxylic acid having the general formula III: in which R has the same meaning as above with an unsaturated derivative of aromatic nature selected from the group consisting in thiophene, 2-methoxynaphthalene, 1,2-methylenedioxy-benzene, and the substituted aromatic hydrocarbons having the general formula IV: STR2 in which R1, R2 have the same meanings as above, possibly within a compatible organic solvent.
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- An Efficient and Remarkably Regioselective Synthesis of Benzocyclobutenones from Benzynes and 1,1-Dimethoxyethylene
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New efficient methodology for the synthesis of substituted benzocyclobutenones is presented that involves the cycloaddition of various substituted benzynes to 1,1-dimethoxyethylene followed by hydrolysis to the corresponding ketone.In most cases studied a high degree of regioselectivity was observed.These observations are consistent with a nonsynchronous mechanism wherein steric and inductive considerations can be used to account for the products observed.
- Stevens, Robert V.,Bisacchi, Gregory S.
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p. 2393 - 2396
(2007/10/02)
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- A New Synthesis of Septicine, a Secophenanthroindolizine Alkaloid
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Septicine , an alkaloid isolated from Ficus septica and Tylophora asthmatica, has been synthesized using 2-(3',4'-dimethoxyphenacyl)pyrrolidine (6) and 3,4-dimethoxy-phenylacetyl chloride (11) as the essential intermediates.Condensation of 6 and 11 affords 2-(3',4'-dimethoxyphenacyl)-N-(3'',4''-dimethoxyphenylacetyl)pyrrolidine (12) which on treatment with potassium-t-butoxide furnishes 6,7-di-(3',4'-dimethoxyphenyl)-5-oxo-1,2,3,5,8,8a-hexahydroindolizine (13).LAH reduction of 13 affords septicine (1), identical (co-TLC, IR, PMR, m.m.p.) with a natural sample.
- Mangla, V. K.,Bhakuni, D. S.
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p. 748 - 749
(2007/10/02)
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- Process for the manufacture of pure isoquinoline derivatives
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In the production of perparine or papaverine and their hydrochlorides, the formation of impurities in the reaction mixture is suppressed by fractionating a 3,4-di-R-benzyl-cyanide in the presence of an organic base (e.g. pyridine, dimethylformamide, ethylenediamine or triethylamine) followed by hydrogenation with a Raney-nickel catalyst treated with aqueous ammonium carbonate solution. R is methoxy or ethoxy.
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- Preparing carboxylic acids from glycidonitriles through enol acylates
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Process for preparing carboxylic acids by converting a glycidonitrile to the enol acylate via hydrohalogenation, acylation and dehydrohalogenation procedures, and conversion of the enol acylate to the carboxylate salt with a base and of the salt to the carboxylic acid with acid. Cyanide content in the mixture is destroyed by adding persulfate or hypochlorite salts. This process, can be used, e.g., to prepare 2-(4'-isobutylphenyl)propionic acid, now known generically as ibuprofen, a highly active anti-inflammatory drug, as well as a host of other useful carboxylic acids.
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