- Dendrimer disassembly by benzyl ether depolymerization
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The disassembly of dendritic structures was realized by a cascade cleavage reaction triggered by an initially stimulated group in the dendrimer periphery. A depolymerizable backbone was engineered into prototypical dendritic structures. Evidence for the completion of the disassembly process is provided by the absorbance peak of the p-nitrophenoxide ion that was intentionally installed at the focal point of the dendrons. Observation of the UV spectra during the disassembly process supports a stepwise cascade cleavage proceeding from the periphery into the core. Copyright
- Li, Sheng,Szalai, Michael L.,Kevwitch, Robert M.,McGrath, Dominic V.
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Read Online
- Scalable Asymmetric Syntheses of Foslevodopa and Foscarbidopa Drug Substances for the Treatment of Parkinson's Disease
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Foslevodopa (FLD, levodopa 4′-monophosphate, 3) and foscarbidopa (FCD, carbidopa 4′-monophosphate, 4) were identified as water-soluble prodrugs of levodopa (LD, 1) and carbidopa (CD, 2), respectively, which are useful for the treatment of Parkinson's disease. Herein, we describe asymmetric syntheses of FLD (3) and FCD (4) drug substances and their manufacture at pilot scale. The synthesis of FLD (3) employs a Horner-Wadsworth-Emmons olefination reaction followed by enantioselective hydrogenation of the double bond as key steps to introduce the α-amino acid moiety with the desired stereochemistry. The synthesis of FCD (4) features a Mizoroki-Heck reaction followed by enantioselective hydrazination to install the quaternary chiral center bearing a hydrazine moiety.
- Ashok, Abhishek,Balaraman, Selvakumar,Bellettini, John R.,Cardinal-David, Benoit,Chan, Vincent S.,Ghosh, Soma,Hill, David R.,Huters, Alexander D.,Ji, Jianguo,Klix, Russell C.,Kotecki, Brian J.,Matulenko, Mark A.,Reddy, Rajarathnam E.,Shou, Minshan,Simanis, Justin,Stambuli, James,Towne, Timothy B.,Voight, Eric A.
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Read Online
- Total synthesis of leontopodioside A
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Leontopodioside A, isolated from the whole plants of Leontopodium leontopodioides, possesses significant α-glucosidase inhibitory activity. In this work, we studied the total synthesis of leontopodioside A by two strategies for the first time. The optimized strategy involved nine linear steps and has an overall yield of 16.1%. The key feature of the strategy is that glycosylation of chalcone acceptor first followed by the cyclization to construct the flavone scaffold, which has general applicability for the synthesis of flavonoid glycosides.
- Yan, Shiqiang,Zhu, Yueyue,Wang, Yujie,Xiao, Qiang,Ding, Ning,Li, Yingxia
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supporting information
(2020/04/08)
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- Drug compound for treating hepatopathy and application thereof
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The invention discloses a drug compound for treating hepatopathy and application thereof. The drug compound specifically serves as a compound shown in general formula (I) or an optical isomer or a pharmaceutically-acceptable salt of the compound. The compound or the optical isomer or the pharmaceutically-acceptable salt of the compound has a good curative effect and low toxicity on hepatopathy, especially fatty liver. Experiments show that the compound has an obvious protective effect on zebrafish nonalcoholic fatty liver, so that the drug compound has a good application prospect in medicinesfor treatment or prevention of hepatopathy, especially fatty liver or liver fibrosis or liver cirrhosis.
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- Synthesis of a Photo-Caged DOPA Derivative by Selective Alkylation of 3,4-Dihydroxybenzaldehyde
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Natural and synthetic polymers containing the catechol moiety of noncoded amino acid 3,4-dihydroxyphenylalanine (DOPA) are capable of metal-coordination and adhesion under wet conditions. Masking the catechol subunit with a photo-cleavable group would provide an opportunity to design tunable adhesion properties that are especially important for biomaterial and biomedicine applications. Herein, we report the regioselective synthesis of a photo-caged DOPA bearing an ortho-nitrobenzyl (oNB) group that is capable of undergoing cleavage upon irradiation with UV light. We developed a selective synthetic route towards a 3-O-oNB alkylated DOPA regioisomer that can be readily incorporated into proteins by using a previously developed bio-expression platform. The synthesis is based on a regioselectivity switch in 3,4-dihydrozybenzaldehyde alkylation upon application of different equivalents of deprotonating base. The enantiomerically pure 3-O-oNB-DOPA was prepared on a gram scale and proved to be generally compatible with the solid-phase peptide synthesis conditions. We also demonstrate the general applicability of the developed synthetic strategy by providing the synthesis of 3-O-methyl-DOPA.
- Schneider, Tobias,Kubyshkin, Vladimir,Budisa, Nediljko
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p. 2053 - 2063
(2018/05/31)
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- PYRROLOBENZODIAZEPINES AND CONJUGATES THEREOF
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A conjugate of formula (A): Wherein Y is selected from formulae A1 and A2: Z1 is a C1-3 alkylene group; Z2 is a C1-3 alkylene group; Q is: where QX is such that Q is an amino-acid residue, a dipeptide residue or a tripeptide residue; L is a linker connected to a cell binding agent; CBA is the cell binding agent; and n is an integer between 0 and 48.
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Page/Page column 154; 155
(2016/04/20)
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- A Corey–Seebach Macrocyclisation Strategy for the Synthesis of Riccardin C and an Unnatural Macrocyclic Bis(bibenzyl) Analogue
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A total synthesis of riccardin C has been accomplished using a Corey–Seebach reaction to effect macrocyclisation. The versatility of the strategy has also been demonstrated with a mimetic synthesis of an unnatural bis(bibenzyl) analogue.
- Almalki, Faisal A.,Harrowven, David C.
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p. 5738 - 5746
(2016/12/14)
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- Design, synthesis and anti-proliferative effects in tumor cells of new combretastatin A-4 analogs
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Abstract A total of 11 novel combretastatin A-4 (CA-4) analogs were designed, synthesized, and evaluated for the anti-proliferative effects in tumor cells. The compounds represent four structural classes: (i) hydrogenated derivatives, (ii) ethoxyl derivatives, (iii) amino derivatives and (iv) pro-drugs. Biological evaluations demonstrate that multiple structural features control the biological potency. Three of the compounds, sit-1, sit-2 and sit-3, have potent anti-proliferative activity against multiple cancer cell lines. Their pro-drugs were synthesized to increase water solubility. Structure-activity relationship study and Surflex-Docking were studied in this paper. These results will be useful for the design of new CA-4 analogs that are structurally related to the SAR study.
- Zhao, Lei,Zhou, Jiu-Jiu,Huang, Xin-Ying,Cheng, Li-Ping,Pang, Wan,Kai, Zhen-Peng,Wu, Fan-Hong
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p. 993 - 999
(2015/08/19)
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- Unexpected copper mediated benzyl O→O migration during an Ullmann ether coupling
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The synthesis of a highly functionalized phenolic diaryl ether 5,5′-oxybis(4-hydroxy-3-methoxybenzaldehyde) (1) potentially interesting as a new scaffold for drug design, has been carried out using Ullmann coupling conditions. An unusual benzyl migration in o-benzyloxyphenol moiety occurred during this reaction leading to an unexpected compound identified as 4-(benzyloxy)-3-(2-(benzyloxy)-4-formyl-6-methoxyphenoxy)-5-methoxy benzaldehyde (7). A rationale for this migration process is proposed.
- Vanucci-Bacqué, Corinne,Chaabouni, Slim,Fabing, Isabelle,Bedos-Belval, Florence,Baltas, Michel
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p. 528 - 530
(2014/01/06)
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- NOVEL FLAVONOID COMPOUNDS AND USES THEREOF
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The present disclosure provides a compound of the following formula, racemates, enantiomers, prodrugs and salts thereof: Formula (I). Also provided is the use of these compounds for the treatment of ischemia and reperfusion injuries. Further applications include the treatment of diseases caused by cell apoptosis and / or cell necrosis.
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Paragraph 123-125
(2014/05/07)
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- Enantioselective synthesis of orthogonally protected (2R,3R)-(-)- epicatechin derivatives, key intermediates in the de novo chemical synthesis of (-)-epicatechin glucuronides and sulfates
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Ten orthogonally protected (-)-epicatechin and 3′- or 4′-O-methyl-(-)-epicatechin derivatives were prepared in a regiospecific and enantioselective manner. For each orthogonally protected (-)-epicatechin derivative, one specific phenolic hydroxyl was protected with a methoxymethyl (MOM) or p-methoxybenyzl (PMB) group and the remainder were protected as benzyl ethers. These uniquely protected (-)-epicatechin derivatives were designed to facilitate the regiospecific installation of a glucuronic acid or sulfate unit onto (-)-epicatechin after selective removal of the MOM or PMB protecting group to provide authentic standards of (-)-epicatechin glucuronides and sulfates.
- Zhang, Mingbao,Erik Jagdmann Jr.,Van Zandt, Michael,Beckett, Paul,Schroeter, Hagen
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p. 362 - 373
(2013/06/27)
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- Epicatechin B-ring conjugates: First enantioselective synthesis and evidence for their occurrence in human biological fluids
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Herein, the first enantioselective total synthesis of a number of biologically relevant (-)-epicatechin conjugates is described. The success of this synthesis relied on (i) optimized conditions for the stereospecific cyclization step leading to the catechin C ring; on (ii) efficient conjugation reactions; and on (iii) optimized deprotection sequences. These standard compounds have been subsequently used to elucidate for the first time the pattern of (-)-epicatechin conjugates present in four different human biological fluids following (-)-epicatechin absorption.
- Romanov-Michailidis, Fedor,Viton, Florian,Fumeaux, René,Lévèques, Antoine,Actis-Goretta, Lucas,Rein, Maarit,Williamson, Gary,Barron, Denis
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supporting information; experimental part
p. 3902 - 3905
(2012/09/22)
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- Shorter synthesis of trifunctionalized cryptophane - A derivatives
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Efficient syntheses of trisubstituted cryptophane-A derivatives that are versatile host molecules for many applications are reported. Trihydroxy cryptophane was synthesized in six or seven steps with yields as high as 9.5%. By a different route, trihydrox
- Taratula, Olena,Hill, P. Aru,Bai, Yubin,Khan, Najat S.,Dmochowski, Ivan J.
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supporting information; experimental part
p. 1414 - 1417
(2011/05/13)
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- First synthesis, characterization, and evidence for the presence of hydroxycinnamic acid sulfate and glucuronide conjugates in human biological fluids as a result of coffee consumption
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A systematic investigation of the human metabolism of hydroxycinnamic acid conjugates was carried out. A set of 24 potential human metabolites of coffee polyphenols has been chemically prepared, and used as analytical standards for unequivocal identifications. These included glucuronide conjugates and sulfate esters of caffeic, ferulic, isoferulic, m-coumaric and p-coumaric acids as well as their dihydro derivatives. A particular focus has been made on caffeic and 3,4-dihydroxyphenylpropionic acid derivatives, especially the sulfate conjugates, for which regioselective preparation was particularly challenging, and have so far never been identified as human metabolites. Ten out of the 24 synthesized conjugates have been identified in human plasma and/or urine after coffee consumption. A number of these conjugates were synthesized, characterized and detected as hydroxycinnamic acid metabolites for the first time. This was the case of dihydroisoferulic acid 3′-O-glucuronide, caffeic acid 3′-sulfate, as well as the sulfate and glucuronide derivatives of 3,4-dihydroxyphenylpropionic acid.
- Fumeaux, Rene,Menozzi-Smarrito, Candice,Stalmach, Angelique,Munari, Caroline,Kraehenbuehl, Karin,Steiling, Heike,Crozier, Alan,Williamson, Gary,Barron, Denis
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experimental part
p. 5199 - 5211
(2010/12/25)
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- Microwave assisted convenient and facile regeneration of carbonyl compounds from semicarbazones, phenylhydrazones and tosylhydrazones using phosphoric acid in solvent-free conditions
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Microwave irradiation of semicarbazones, phenylhydrazones and tosylhydrazones of carbonyl compounds with phosphoric acid under solvent-free conditions provides a fast, efficient and simple method for regeneration of carbonyls in excellent yields.
- Banerjee, Krishna,Mitra, Alok Kumar,Patra, Amarendra
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p. 537 - 539
(2007/10/03)
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- IMIDAZOPYRAZINE TYROSINE KINASE INHIBITORS
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Compounds of the formula (I) and pharmaceutically acceptable salts thereof, wherein Q1 and R1 are defined herein, inhibit the IGF-1R enzyme and are useful for the treatment and/or prevention of various diseases and conditions that respond to treatment by inhibition of tyrosine kinases.
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Page/Page column 187-188
(2008/06/13)
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- Benzylidene thiazolidinediones and their use as antimycotic agents
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A compound of formula I or a salt thereof wherein, A is O or S, X and Y independently represent O, CH2 and may be the same or different, Q is (CH2)m—CH(R1)—(CH2)n, R is OR6, NHR8, R1 is hydrogen, or optionally substituted alkyl, R2 and R3 are independently hydrogen, or specific substituents, provided that R2 and R3 are not both H, and R4 and R5 are hydrogen or specific substituents, m is 0-3; n is 0-2; are useful in the treatment of fungal infections.
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Page/Page column 8-9
(2010/02/05)
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- PIPERIDINE DERIVATIVE COMPOUNDS AND DRUGS CONTAINING THE COMPOUNDS AS THE ACTIVE INGREDIENT
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A piperidine derivative of formula (I) (wherein all symbols are as described in the specification.) and an intermediate for the preparation thereof The compound of formula (I) has phosphodiesterase 4 inhibitory activity, and it is useful for the prevention and/or treatment of inflammatory diseases, diabetic diseases, allergic diseases, autoimmune diseases, ocular diseases, osteoporosis, bone fracture, osteoarthritis, obesity, bulimia, depression, Parkinson's disease, dementia, ischemia-reperfusion injury, leukemia, acquired immunodeficiency deficiency syndrome (AIDS), shock, systemically inflammatory responsive diseases (SIRS), etc.
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- 1,2-AZOLE DERIVATIVES WITH HYPOGLYCEMIC AND HYPOLIPIDEMIC ACTIVITY
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A compound represented by the formula (1) wherein ring A is a ring optionally having 1 to 3 substituents; ring B is a 1,2-azole ring which may further have 1 to 3 substituents; Xa, Xb and Xc are the same or different and each is a bond, - O -, - S - and the like; Ya is a divalent aliphatic hydrocarbon residue having 1 to 20 carbon atoms; Yb and Yc are the same or different and each is a bond or a divalent aliphatic hydrocarbon residue having 1 to 20 carbon atoms; ring C is a monocyclic aromatic ring which may further have 1 to 3 substituents; and R represents -OR4 (R4 is hydrogen atom or optionally substituted hydrocarbon group) and the like, or a salt thereof or a prodrug thereof is useful as an agent for the prophylaxis or treatment of diabetes and the like.
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- Preparation of phosphatase inhibitors
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Disclosed are compounds of the Formula I and pharmaceutically acceptable salts and prodrugs thereof, wherein A, B, R1, R2, R3, R4 and R5 are as defined in the specification. Such compounds are tyrosine phosphatase inhibitors and useful in the treatment or prevention of Type II Diabetes Mellitus. Also encompassed by the invention are formulations comprising the noted compounds, processes for preparing such compounds, a method for treating or preventing Type II Diabetes Mellitus.
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- Supramolecular fullerene chemistry: A comprehensive study of cyclophane-type mono- and bis-crown ether conjugates of C70
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The covalently templated bis-functionalization of C70, employing bis-malonate 5 tethered by an anti-disubstituted dibenzo[18]crown-6 (DB18C6) ether, proceeds with complete regiospecificity and provides two diastereoisomeric pairs of enantiomeric C70 crown ether conjugates, (±)-7a and (±)-7b, featuring a five o'clock bis-addition pattern that is disfavored in sequential transformations (Scheme 1). The identity of (±)-7a was revealed by X-ray crystal-structure analysis (Fig. 6). With bis-malonate 6 containing a syn-disubstituted DB18C6 tether, the regioselectivity of the macrocylization via double Bingel cyclopropanation changed completely, affording two constitutionally isomeric C70 crown ether conjugates in a ca. 1:1 ratio featuring the twelve (16) and two o'clock ((±)-15) addition patterns, respectively (Scheme 3). The X-ray crystal-structure analysis of the twelve o'clock bis-adduct 16 revealed that a H2O molecule was included in the crown ether cavity (Figs. 7 and 8). Two sequential Bingel macrocyclizations, first with anti-DB18C6-tethered (5) and subsequently with syn-DB18C6-tethered (6) bis-malonates, provided access to the first fullerene bis-crown ether conjugates. The two diastereoisomeric pairs of enantiomers (±)-28a and (±)-28b were formed in high yield and with complete regioselectivity (Scheme 9). The cation-binding properties of all C70 crown-ether conjugates were determined with the help of ion-selective electrodes (ISEs). Mono-crown ether conjugates form stable 1:1 complexes with alkali-metal ions, whereas the tetrakis-adducts of C70, featuring two covalently attached crown ethers, form stable 1:1 and 1:2 host-guest complexes (Table 2). Comparative studies showed that the conformation of the DB18C6 ionophore imposed by the macrocyclic bridging to the fullerene is not particularly favorable for strong association. Reference compound (±)-22 (Scheme 4), in which the DB18C6 moiety is attached to the C70 sphere by a single bridge only and, therefore, possesses higher conformational flexibility, binds K+ and Na+ ions better by factors of 2 and 20, respectively. Electrochemical studies demonstrate that cation complexation at the crown ether site causes significant anodic shifts of the first reduction potential of the appended fullerene (Table 3). In case of the C70 mono-crown ether conjugates featuring a five o'clock functionalization pattern, addition of 1 equiv. of KPF6 caused an anodic shift of the first reduction wave in the cyclic voltammogram (CV) by 70 to 80 mV, which is the result of the electrostatic effect of the K+ ion bound closely to the fullerene core (Fig. 14). Addition of 2 equiv. of K+ ions to C70 bis-crown ether conjugates resulted in the observation of only one redox couple, whose potential is anodically shifted by 170 mV with respect to the corresponding wave in the absence of the salt (Fig. 16). The synthesis and characterization of novel tris- and tetrakis-adducts of C70 are reported (Schemes 5 and 6). Attempts to prepare even more highly functionalized derivatives resulted in the formation of novel pentakis- and hexakis-adducts and a single heptakis-adduct (Scheme 7), which were characterized by 1H- and 13C-NMR spectroscopy (Fig. 10), as well as matrix-assisted laser-desorption-ionization mass spectrometry (MALDI-TOF-MS). Based on predictions from density-functional-theory (DFT) calculations (Figs. 12 and 13), structures are proposed for the tris-, tetrakis-, and pentakis-adducts.
- Van Eis, Maurice J.,Seiler, Paul,Muslinkina, Liya A.,Badertscher, Martin,Pretsch, Ernoe,Diederich, Francois,Alvarado, Robert J.,Echegoyen, Luis,Nunez, Ignacio Perez
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p. 2009 - 2055
(2007/10/03)
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- Development of a novel hapten for radioimmunoassay of the lignan, enterolactone in plasma (Serum). Total synthesis of (±)-trans-5- carboxymethoxyenterolactone and several analogues
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A recently developed method for the analysis of the mammalian lignan, enterolactone 1, is based on time-resolved fluoroimmunoassay (TR-FIA) using an europium chelate as a label. This RIA utilizes enterolactone derivatives carrying a carboxylic acid appendage for the production of antiserum and tracer. The synthesis of 5-carboxymethoxyenterolactone 6 and analogues 5, 7 and 8 is described, and their suitability for the method are discussed. (C) 2000 Elsevier Science Ltd.
- M?kel?, Taru,Matikainen, Jorma,W?h?l?, Kristiina,Hase, Tapio
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p. 1873 - 1882
(2007/10/03)
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- A convenient synthesis of phosphate esters of dopamine and epinine
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The title compounds were prepared with a route which is characterized by the regioselective preparation of 3 or 4 oxydryl protected dopamine and epinine precursors.
- Santangelo, Francesco,Casagrande, Cesare
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p. 2863 - 2873
(2007/10/03)
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- New Agents of Biaryl Oxidative Coupling in Fluoro Acid Medium. VI. Application to the Synthesis of Phenolic Bisbenzocyclooctadiene Lignans
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A systematic study of redox couples in fluoro acid medium has been carried out for the oxidative coupling of bisbenzocyclooctadiene lignan precursors.Tl2O3 and Re2O7 were found to be the more efficient reagents with precursors possessing methylenedioxy substituents for the former and only methoxy groups for the latter.Finally, oxidative coupling of a phenolic dibenzylbutane led to a mixture of two BBCOD's, resulting from para and ortho coupling to the phenolic group. - Keywords: Bisbenzocyclooctadienes, Biaryls, Dibenzylbutanolides, Dibenzylbutanes, Phenolic coupling.
- Planchenault, Denis,Dhal, Robert,Robin, Jean-Pierre
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p. 1395 - 1404
(2007/10/02)
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- Method for improving the absorption and effectiveness of a catecholamine compound
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A catecholamine compound is converted to a new mono O-phosphate ester derivative thereof which exhibit improved absorption and effectiveness.
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- Complexation of Diquat by a Regiospecifically Synthesised Macrobicyclic Receptor Molecule
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An X-ray structural investigation has shown that the macrobicyclic host (1), synthesised regiospecifically from 3,4-dihydroxybenzaldehyde (2) in eight steps, forms a deep red 1:1 crystalline complex with Diquat in which the guest dication is encapsulated by the host.
- Allwood, Billy L.,Kohnke, Franz H.,Slawin, Alexandra M. Z.,Stoddart, J. Fraser,Williams, David J.
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p. 311 - 314
(2007/10/02)
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