- Enantioselective synthesis of δ-ketobutanolides from (L)-glutamic acid via organomanganese reagents
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Various optically active δ-ketobutanolides were easily prepared in good yields, with an excellent enantiomeric purity, by acylation of organomanganese reagents with the butyrolactone acid chloride 3 prepared from natural (L)-glutamic acid. The reaction takes place in THF under mild conditions (-10°C, 3h or 3% CuCl, -30°C, 20 min.).
- Cahiez, Gerard,Metais, Eric
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Read Online
- Stereoisomeric flavour compounds. LXIII. 4-Hydroxypentan-2-one enantiomers - Structure and properties
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From racemic 4-hydroxypentan-2-one and (S)-tetrahydro-5-oxo-2-furancarboxylic acid chloride the corresponding diastereomeric esters were generated, subsequently separated by liquid chromatography and hydrolyzed to yield pure enantiomers of 4-hydroxypentan-2-one. The X-ray crystal structures of the diastereomeric esters as well as the odour impression of the pure 1,3-ketol enantiomers are reported.
- Bensch,Mosandl,Fischer
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- Synthesis of four diastereomers of sclerophytin F and structural reassignment of several sclerophytin natural products
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Synthesis of the triol that has been proposed to be the marine natural product sclerophytin F has been completed along with the syntheses of three diastereomers. Comparison of the NMR spectroscopic data for all four compounds to the data reported for the natural product reveals that sclerophytin F is not the 3S diastereomer of sclerophytin A as proposed by Friedrich and Paquette. Re-analysis of the NMR spectroscopic data for known sclerophytin natural products and synthetic analogues leads to the conclusion that sclerophytins E and F are the same compound. This finding has allowed structural reassignment of several other cladiellin natural products.
- Clark, J. Stephen,Delion, La?titia,Farrugia, Louis J.
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- Stereocontrolled Synthesis of 2,5-Linked Monotetrahydrofuran Units of Acetogenins
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An approach to the stereocontrolled monotetrahydrofuran units of acetogenins is described.The NMR data of the two synthesized diastereoisomers 11 and 12 allow us to define the relative configuration of the monotetrahydrofuran acetogenins.
- Harmange, Jean-Christophe,Figadere, Bruno,Cave, Andre
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- Stereoselective synthesis of zooxanthellactone
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The marine polyunsaturated natural product zooxanthellactone was synthesized in six steps and in 11% overall yield from eicosapentaenoic acid. The key synthetic steps were a Sonogashira cross-coupling reaction and a stereoselective semi-reduction. These efforts, together with NMR and optical rotation data, confirmed the reported structure of zooxanthellactone.
- Jakobsen, Martin Gjerde,Vik, Anders,Hansen, Trond Vidar
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- Construction the a-b bicyclic ring structure of stemocurtisine
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In this paper, the synthesis of the A-B bicyclic ring structure 3 of the natural product Stemocurtisine is described. The synthesis was accomplished in seven synthetic steps from com-mercially available L-glutamic acid. The key step involved a borono-Mannich reaction between the hemiaminal 6 and trans-β-styryl boronic acid and trans-β-styrylpotassiumtrifluoroborate to prepare the cis diene 4. Attempts to prepare the A-B-C ring compound 2 via intramolecular epox-ide ring opening followed by rearrangement under different basic conditions were unsuccessful. The only unreactive starting material was recovered.
- Xuan, Duc Dau
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- NOVEL SUBSTITUTED AMINOTHIAZOLOPYRIMIDINEDIONE FOR THE TREATMENT AND PROPHYLAXIS OF VIRUS INFECTION
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The present invention relates to compounds of formula (I), wherein R1 to R4 are as described herein, and their pharmaceutically acceptable salts, enantiomers or diastereomers thereof, and compositions including the compounds for use
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- NOVEL 3-SUBSTITUTED 5-AMINO-6H-THIAZOLO[4,5-D]PYRIMIDINE-2,7-DIONE COMPOUNDS FOR THE TREATMENT AND PROPHYLAXIS OF VIRUS INFECTION
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The present invention relates to compounds of formula (I), wherein R1, R2 and R3 are as described herein, and their prodrugs or pharmaceutically acceptable salt, enantiomer or diastereomer thereof, and compositions including the compounds and methods of using the compounds.
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- NOVEL SUBSTITUTED AMINOTHIAZOLOPYRIMIDINEDIONE FOR THE TREATMENT AND PROPHYLAXIS OF VIRUS INFECTION
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The present invention relates to compounds of formula (I), wherein R1 to R5 are as described herein, and their prodrugs or pharmaceutically acceptable salt, enantiomer or diastereomer thereof, and compositions including the compounds and methods of using the compounds.
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- Enantiopure chelating agents for chelator coupled pharmaceuticals, corresponding preparation method thereof and chelator coupled pharmaceuticals
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According to the present invention an enantiopure chelating compound of general Formula 10A or 10B is provided: wherein each of R1 through R3 is independently selected hydrogen, substituted or unsubstituted C1-C20 alkyl, substituted or unsubstituted C2-C20 alkenyl, substituted or unsubstituted C2-C20 alkynyl, substituted or unsubstituted C3-C10 cycloalkyl, substituted or unsubstituted C6-C60 aryl, or -Si(R4)(R5)(R6), and each of R4 through R6 is independently selected a substituted or unsubstituted group consisting of C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C1-C20 alkoxy, C3-C10 cycloalkyl, C6-C60 aryl, and C6-C60 aryloxy. The present invention further refers to a corresponding preparation method of the chelating compound and chelator coupled pharmaceuticals including the same.
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Paragraph 0033
(2016/08/17)
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- Stereoselective synthesis of (-)-desethyleburnamonine, (-)-vindeburnol and (-)-3-epitacamonine: Observation of a substrate dependent diastereoselectivity reversal of an aldol reaction
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Starting from (-)-acetoxyglutarimide, the enantioselective multistep synthesis of (-)-desethyleburnamonine, (-)-vindeburnol and (-)-3-epitacamonine has been demonstrated via a common hydroxyl-lactam intermediate with very good overall yields. The acetoxy function from (-)-acetoxyglutarimide was initially used as a handle to induce enantioselectivity and then as a latent source of the ketone carbonyl group. Most importantly, substrate dependent reversal of the diastereoselectivity in ester aldol reactions of hexahydroindolo[2,3-a]quinolizinones has been reported.
- Mondal, Pravat,Argade, Narshinha P.
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p. 10394 - 10406
(2016/11/18)
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- Total Synthesis of (-)-N-Methylwelwitindolinone C Isothiocyanate Based on a Pd-Catalyzed Tandem Enolate Coupling Strategy
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The highly stereocontrolled total synthesis of (-)-N-methylwelwitindolinone C isothiocyanate is described, which features the expeditious construction of a bicyclo[4.3.1]decane ring system by a palladium-catalyzed tandem enolate allylation/arylation reaction.
- Komine, Keita,Nomura, Yusuke,Ishihara, Jun,Hatakeyama, Susumi
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supporting information
p. 3918 - 3921
(2015/08/18)
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- Synthesis of perfluorinated analogs of DOTA and NOTA: Bifunctional chelating groups with potential applications in hybrid molecular imaging
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The synthesis of novel NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid) and DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) chelating groups bearing perfluorinated appendages is described. DOTA and NOTA groups are used in the production
- Hoareau, Rapha?l,Scott, Peter J.H.
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p. 5755 - 5757
(2013/09/24)
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- Asymmetric total synthesis of (+)-swainsonine
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A concise asymmetric synthesis of (+)-swainsonine (ent-1) is described starting from 2, which was readily prepared from commercially available l-glutamic acid. The method features installation of the indolizidine ring via an intramolecular cyclisation of
- Chooprayoon, Soontorn,Kuhakarn, Chutima,Tuchinda, Patoomratana,Reutrakul, Vichai,Pohmakotr, Manat
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experimental part
p. 531 - 537
(2011/02/28)
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- Radical cyclizations of acylsilanes in the synthesis of (+)-swainsonine and formal synthesis of (-)-epiquinamide
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Radical cyclization of acylsilane is an useful synthetic methodology. To demonstrate the versatility of this method using the cyclization as a key step, polyhydroxylated indolizidine (+)-swainsonine was synthesized through two different bond connection ap
- Chen, Ming-Jen,Tsai, Yeun-Min
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experimental part
p. 1564 - 1574
(2011/04/15)
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- The enantioselective total synthesis of nemotin
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The allene-diyne natural product nemotin was synthesized for the first time through an enantioselective route with the stereogenic center at the lactone moiety derived from l-glutamic acid and the allene axis constructed from the corresponding propargylic
- Jian, Ya-Jun,Wu, Yikang
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experimental part
p. 811 - 821
(2010/06/20)
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- Asymmetric syntheses of 6-deoxyfagomin, d-deoxyrhamnojirimycin, and d-rhamnono-1,5-lactam
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N-Allyl protected 3-O-benzyloxglutarimide 11 was synthesized as a useful variant of the chiral building block 10. This modification allowed a high-yielding deprotection of the allyl group from the lactam intermediate 14. Starting from this building block,
- Fu, Rui,Du, Yu,Li, Zhao-Ying,Xu, Wei-Xuan,Huang, Pei-Qiang
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experimental part
p. 9765 - 9771
(2010/01/16)
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- Development of a multigram asymmetric synthesis of 2-(R)-2-(4,7,10-tris tert-butylcarboxymethyl-1,4,7,10-tetraazacyclododec-1-yl)-pentanedioic acid, 1-tert-butyl ester, (R)-tert-Bu4-DOTAGA1
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A process for the multigram asymmetric synthesis of the chiral tetraazamacrocycle 2-(R)-2-(4,7,10-tris tert-butylcarboxymethyl- 1,4,7,10-tetraazacyclododec-1-yl)-pentanedioic acid, 1-tert-butyl ester ((R)-tert-Bu4-DOTAGA, 4) has been devised and demonstrated. The nine-step synthesis features an improved synthesis of 2-(S)-5- oxotetrahydrofuran- 2-carboxylic acid, tert-butyl ester 8, the precursor to the novel alkylating agent (S)-5-benzyl 1-tert-butyl 2-(methylsulfonyloxy) pentanedioate 12, which was used to introduce an orthogonally protected chiral glutarate arm to the 1,4,7,10-tetraazacyclododecane (cyclen) nucleus in high optical purity. Cyclen derivative (R)-t-Bu4-DOTAGA, 4, a key intermediate for the manufacture of a magnetic resonance imaging (MRI) candidate, was produced with high chemical (≥95%) and optical (ee ≥ 97%) purity. The process developed was successfully applied to the kilogram-scale cGMP synthesis of (R)-t-Bu4-DOTAGA.
- Levy, Stuart G.,Jacques, Vincent,Zhou, Kevin Li,Kalogeropoulos, Shirley,Schumacher, Kelly,Amedio, John C.,Scherer, Jonathan E.,Witowski, Steven R.,Lombardy, Richard,Koppetsch, Karsten
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experimental part
p. 535 - 542
(2010/04/22)
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- Synthesis of iso-epoxy-amphidinolide N and des-epoxy-caribenolide i structures. Initial forays
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Two strategies for the projected total synthesis of the phenomenally potent antitumour macrolides amphidinolide N (1) and caribenolide I (2) are described. The title compounds are introduced as challenging and unique targets for chemical synthesis, and their retrosynthetic analysis is presented. The synthesis of the four defined key building blocks (10, 39, 67 and 72), required for the construction of amphidinolide N (1), in their enantiomerically pure forms, is described, followed by the coupling of 10, 39 and 72 through hydrazone alkylation processes to generate the complete C6-C29 carbon framework of the target compound (1). Fusion of the remaining C1-C5 sector (72) onto the molecule by metathesis-based methods was unsuccessful, resulting in the adoption of a second-generation strategy which called for the employment of one of the array of palladium-catalysed cross-coupling reactions to generate the C5-C6 carbon-carbon bond. Vinyl bromide 125, representing the C6-C29 skeleton of caribenolide I (2), was prepared through the sequential alkylation of hydrazone 10 with bromide 116 and iodide 55, but failed to engage in the appropriate cross-coupling reaction with a variety of C1-C4 partners. Despite these setbacks, the information gleaned from these endeavours was to prove invaluable in laying the foundation for the eventual successful approach to the macrocyclic structures of amphidinolide N (1) and caribenolide I (2). The Royal Society of Chemistry 2006.
- Nicolaou,Brenzovich, William E.,Bulger, Paul G.,Francis, Tasha M.
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p. 2119 - 2157
(2008/02/07)
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- Optically pure and enriched isomers of chelating ligands and contrast agents
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Organic chelating ligands, organic chelating ligand precursors, and metal chelates are disclosed. Methods for synthesizing the same are also described, including methods for preparing optically-enriched or optically-pure compositions of the same.
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Page/Page column 13; 14; sheet 1; 2
(2008/06/13)
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- Asymmetric synthesis of antimalarial alkaloids (+)-febrifugine and (+)-isofebrifugine
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Diastereoselective α,-amidoalkylation of N,O-acetal, derivated from controlled regio and diastereoselective reduction of (S)-N-(4-methoxybenzyl)-3-silyloxyglutarimide provided two diastereomeric 6-allyl-5-silyloxy-2-piperidinones in 76:24 selectivity. The transformation of the major diastereomer into a known advanced intermediate allowed the synthesis of (+)-febrifugine and (+)-isofebrifugine.
- Huang, Pei-Qiang,Wei, Bang-Guo,Ruan, Yuan-Ping
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p. 1663 - 1667
(2007/10/03)
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- Asymmetric synthesis of (+)-L-733, 060 and (+)-CP-99, 994 based on a new chiral 3-piperidinol synthon.
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[reaction: see text] Selective and potent neurokinin substance P receptor antagonists (+)-L-733, 060 (1) and (+)-CP-99, 994 (2) have been synthesized starting from a new (3S)-piperidinol synthon derived from l-glutamic acid. The methods featured a C-2 reg
- Huang, Pei-Qiang,Liu, Liang-Xian,Wei, Bang-Guo,Ruan, Yuan-Ping
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p. 1927 - 1929
(2007/10/03)
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- π-facial selectivity in 1,3-dipolar cycloaddition reactions of α-methylidene-γ-lactone substituted by 4-methyl-2,6,7-trioxabicyclo[2.2.2]Octan-1-yl group in γ-position
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Diastereoselectivity of 1,3-dipolar cycloaddition reactions of benzyl azide, diazomethane, a nitrile oxide and a nitrile imine to α-methylidene-γ-lactone dipolarophile was effectively controlled by a bulky γ-substituent, 4-methyl-2,6,7-trioxabicyclo[2.2.2
- Melsa, Petr,Mazal, Ctibor
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p. 353 - 364
(2007/10/03)
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- Study of the structure-activity relationships of the acetogenin of annonaceae, muricatacin and analogues
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A study of the structure-cytotoxic activity of the acetogenin of Annonaceae, muricatacin 1, is reported. indeed, muricatacin 1 has shown promising antitumoral activity. Therefore several 5-hydroxy-4-alkcanolides were prepared and then tested against KB and VERO cell lines. A few other analogues were synthesized and tested against both cell lines. Thus this work allowed us to better determine the pharmacophore of the molecule and to propose muricatacin 1 instead of a more complicated acetogenin of Annonaceae as a lead compound in the search for new antineoplastic agents.
- Cave,Chaboche,Figadere,Harmange,Laurens,Peyrat,Pichon,Szlosek,Cotte-Lafitte,Quero
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p. 617 - 623
(2007/10/03)
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- A formal stereoselective synthesis of a hydroxyethylene dipeptide isostere
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4-Hydroxy-5-amino-6-phenyl-4-hexanolide has been synthesized under its cyclized form (lactone 5) from a very inexpensive chiral starting material, L-glutamic acid. The key steps were an original reduction of carbonyl of a ketone with n-Bu3SnH i
- Peyrat, Jean-Francois
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p. 2757 - 2760
(2007/10/02)
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- Lactones, part 28: EPC-Synthesis, structure and pharmacology of 'lactonized' and 'lactamized' analogues of acetylcholine
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The enantiopure γ-aminomethyl-γ-butyrolactones (S)- and (R)-4a-d represent constrained analogues of acetylcholine, which were synthesized from D- or L-glutamic acid following two different routes. In addition, the corresponding lactames (S)- and (R)-10 were prepared by enantioselective synthesis. Only moderate activity was found at acetylcholine sites at the guinea pig atrium.
- Pieper,Trankle,Nieger,Mohr,Lehmann
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- Synthesis of Chiral Hydroxylated Quinolizidines via Vinylogous Bischler-Napieralski Nitrilium Ion Cyclizations
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Treatment of the amido esters 9 and 17 with PPSE (polyphosphoric acid trimethylsilyl ester) followed by NaBH4 in ethanol gave the quinolizidinones 11-14 and 19 via a vinylogous Bischler-Napieralski nitrilium ion cyclization-reductive lactamization two-step process.Subsequent ozonolysis and reduction afforded chiral hydroxylated quinolizidines in moderate to good yield.In contrast to five-membered-ring formation, six-membered-ring formation via nitrilium-ion cyclization requires a p-methoxy-substituted styryl terminator.The effect para-substituted styryl terminators have on the energy of activation and ΔH for the cyclization process has been calculated by semiempirical and ab initio methods.
- Marquart, Angela L.,Podlogar, Brent L.,Huber, Edward W.,Demeter, David A.,Peet, Norton P.,et al.
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p. 2092 - 2100
(2007/10/02)
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- MICROBIAL TRANSFORMATION OF (-)-VERNOLIC ACID INTO (4R,5R)-5-HYDROXY-γ-DECALACTONE
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(-)-Vernolic acid, isolated and purified from seeds of Euphorbia lagascae was administered to cultures of Sporobolomyces odorus. (4R,5R)-5-Hydroxy-γ-decalactone 1 accumulated as the main product.The configuration of the product was determined by synthesis of all four stereoisomers and comparison of spectroscopic and chromatographic data.
- Albrecht, Wolfgang,Tressl, Roland
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p. 1391 - 1396
(2007/10/02)
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- Studies of HIV-1 protease inhibitors. II. Incorporation of four types of hydroxyethylene dipeptide isosteres at the scissile site of substrate sequences
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Human immunodeficiency virus type 1 (HIV-1) protease inhibitors containing four types of hydroxyethylene dipeptide isosteres were designed and synthesized. These inhibitors consist of eight stereoisomers of phenylalanylproline (Phe-Ψ[H.E.]-Pro), four ster
- Sakurai,Higashida,Sugano,Nishi,Saito,Ohata,Handa,Komai,Yagi,Nishigaki,Yabe
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p. 1378 - 1386
(2007/10/02)
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- Enantioselective synthesis of (R)- and (S)-5-dimethylaminomethyl-4,5-dihydro-2(3H)-furanone methobromide - Constrained analogues of acetylcholine
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S6 and R6 represent constrained analogues of acetylcholine. Two effective routes to synthesize the enantiopure title compounds starting from either D- or L-glutamic acid are reported.
- Lehmann,Pieper
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p. 1537 - 1538
(2007/10/02)
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- Stereospecific synthesis of (+)-muricatacin: A biologically active acetogenin derivative
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(+)-muricatacin and analogs have been synthesized without ambiguity about the absolute configuration at the C-4 and C-5 centres. The observed [α](D) are reported as well as the results obtained for the cytotoxicity assay with KB and VERO cell lines.
- Figadere,Harmange,Laurens,Cave
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p. 7539 - 7542
(2007/10/02)
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- 5,5-Dialkyl-δ-valerolactone Derivatives as New Chiral Dopants for Ferroelectric Liquid Crystals
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(S)-2-(4'-Octyloxybiphenyl-4-carboxy)-5,5-dipropyl-δ-valerolactone showed interesting properties as the chiral dopant for ferroelectric liquid crystals (FLCs).The FLC mixture containing only 2percent by mol of this compound exhibited the magnitude of spontaneous polarization (Ps) as large as 9.6 nC/cm2 and the response time as fast as 75 μs at 25 deg C in the electric field of +/- 5 V/μm.
- Sakashita, Keiichi,Nakaoka, Yuriko,Ikemoto, Tetsuya,Terada, Fumiko,Kageyama, Yoshitaka,et al.
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p. 1727 - 1730
(2007/10/02)
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- LATERAL ROOT INDUCING COMPOUNDS FROM THE BACTERIUM ERWINIA QUERCINA: ISOLATION, STRUCTURE AND SYNTHESIS
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The structures lateral root inducing compounds produced in culture by the bacterium Erwinia quercina were shown to be two diastereomers of 4,5-dihydroxy-6-phenylhexanoic acid.All four chiral isomers of the active structure were synthesized.
- Wright, Amy E.,Schaefer, Matthias,Midland, Sharon,Munnecke, Donald E.,Sims, James J.
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p. 5699 - 5702
(2007/10/02)
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- SYNTHESIS OF D-AMICETOSE AND L-RHODINOSE FROM L-GLUTAMIC ACID
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L-Glutamic acid has been converted into a separable mixture of D-amicetono- and L-rhodinono-γ-lactones by a sequence involving transformation into (S)-γ-carboxy-γ-butyrolactone (2), conversion of 2 into the corresponding methyl ketone by the diazoketone route, and selective reduction with zinc borohydride or boranemethyl sulfide.Reduction of the two lactones with di-isobutylaluminium hydride gave the corresponding deoxy sugars.In spite of some improvements in the preparation of 2, the optical yield of this step was only ca. 80percent, but one crystallisation from chloroform raised the optical purity to 96percent.The subsequent steps produced a loss in optical purity of only 4percent.
- Berti, Giancarlo,Caroti, Paola,Catelani, Giorgio,Monti, Luigi
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