- Total synthesis of violaceimides A–E and consideration of the reported stereochemistry
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Here we report the first total synthesis of violaceimides A–E, a family of sulfur-containing metabolites from Aspergillus violaceus, a sponge-associated fungus. A concise, convergent and enantioselective synthesis was developed for all five family members
- Perry, Charles K.,Fulton, Mark G.,Lindsley, Craig W.
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- Pyrazolopyrimidine derivative, preparation method, pharmaceutical composition and application
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The invention discloses a pyrazolopyrimidine derivative, a preparation method, a pharmaceutical composition and application. The invention provides the pyrazolopyrimidine derivative as shown in a formula I and stereoisomer or solvate or pharmaceutically acceptable salts or active metabolite or prodrug thereof. The pyrazolopyrimidine derivative as shown in the formula I has good inhibitory activity on Bruton's tyrosine kinase (Btk) and particularly has good in vitro and in vivo inhibitory activity on growth of tumor cells, and a good marketization prospect is achieved. Please see the formula I in the description.
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Paragraph 0307; 0308; 0309
(2017/07/19)
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- Practical asymmetric synthesis of an edivoxetine·HCl intermediate via an efficient diazotization process
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A convergent synthesis of (S)-(4-benzylmorpholin-2-yl)(morpholino)methanone methanesulfonate (1), a key regulatory starting material for edivoxetine·HCl, was developed at Eli Lilly & Company. This novel synthesis utilizes d-serine as the source of chirali
- Kopach, Michael E.,Heath, Perry C.,Scherer, Roger B.,Pietz, Mark A.,Astleford, Bret A.,McCauley, Mary Kay,Singh, Utpal K,Wong, Sze Wing,Coppert, David M.,Kerr, Mark S.,Houghton, Peter G.,Rhodes, Gary A.,Tharp, Gregg A.
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p. 543 - 550
(2015/04/27)
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- Total Synthesis of Solandelactone i
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Since the marine natural products solandelactones A-I were isolated from the hydroid Solanderia secunda and investigated by Seo et al. in 1996, considerable synthetic efforts toward these marine oxylipins followed. However, the structure elucidation of solandelactone I remained incomplete, and no synthesis has been reported. On the basis of our retrosynthetic analysis, the key building blocks were combined in a Horner-Wadsworth-Emmons reaction to create two common intermediates for the stereodivergent synthesis of all four diastereomers 1-4 matching the proposed structure of solandelactone I. Comparison of the published analytical data of natural product solandelactone I and data obtained from the synthetic endeavor toward diastereomers 1-4 enabled the structure assignment of isomer 3; the proposed biosynthetic pathway for marine oxylipins also supports the result.
- Eichenauer, Nils C.,Tschersich, Roxanne,Pietruszka, J?rg
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p. 2782 - 2790
(2015/12/09)
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- Potent inhibitors of a shikimate pathway enzyme from Mycobacterium tuberculosis: Combining mechanism- and modeling-based design
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Tuberculosis remains a serious global health threat, with the emergence of multidrug-resistant strains highlighting the urgent need for novel antituberculosis drugs. The enzyme 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase (DAH7PS) catalyzes the first step of the shikimate pathway for the biosynthesis of aromatic compounds. This pathway has been shown to be essential in Mycobacterium tuberculosis, the pathogen responsible for tuberculosis. DAH7PS catalyzes a condensation reaction between P-enolpyruvate and erythrose 4-phosphate to give 3-deoxy-D-arabino-heptulosonate 7-phosphate. The enzyme reaction mechanism is proposed to include a tetrahedral intermediate, which is formed by attack of an active site water on the central carbon of P-enolpyruvate during the course of the reaction. Molecular modeling of this intermediate into the active site reported in this study shows a configurational preference consistent with water attack from the re face of P-enolpyruvate. Based on this model, we designed and synthesized an inhibitor of DAH7PS that mimics this reaction intermediate. Both enantiomers of this intermediate mimic were potent inhibitors of M. tuberculosis DAH7PS, with inhibitory constants in the nanomolar range. The crystal structure of the DAH7PS-inhibitor complex was solved to 2.35 A. Both the position of the inhibitor and the conformational changes of active site residues observed in this structure correspond closely to the predictions from the intermediate modeling. This structure also identifies a water molecule that is located in the appropriate position to attack the re face of P-enolpyruvate during the course of the reaction, allowing the catalytic mechanism for this enzyme to be clearly defined.
- Reichau, Sebastian,Jiao, Wanting,Walker, Scott R.,Hutton, Richard D.,Baker, Edward N.,Parker, Emily J.
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scheme or table
p. 16197 - 16207
(2012/03/26)
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- Synthesis of optically active N6-alkyl derivatives of (R)-3-(adenin-9-yl)-2-hydroxypropanoic acid and related compounds
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Reaction of ethyl (R)-oxiranecarboxylate (2a) with various nucleobases (adenine, 6-chloropurine, thymine, cytosine, N6-benzoyladenine, 4-methoxy-5-methylpyrimidin-2(1H)-one and 4-methoxypyrimidin-2(1H)-one) afforded ethyl 3-substituted-2-hydroxypropanoates 4-10. Enantioselectivity of this reaction is dependent on the type of the base: 6-chloropurine, N6-benzoyladenine, 4-methoxy-5-methylpyrimidin-2(1H)-one, thymine and cytosine gave optically pure R enantiomers. In other cases, partial or complete racemization occurred. Optically pure ethyl (R)-3-(6-chloropurin-9-yl)-2-hydroxypropanoate (5a) was hydrolyzed to give (R)-3-(6-chloropurin-9-yl)-2-hydroxypropanoic acid (11). Reactions of 11 with various primary or secondary amines led to N6-substituted (R)-3-(adenin-9-yl)-2-hydroxypropanoic acids 14-19. Enantiomeric purity was determined from 1H NMR spectra measured in the presence of (-)-(R)-1-(9-anthryl)-2,2,2-trifluoroethan-1-ol.
- Krecmerova, Marcela,Budesinsky, Milos,Masojidkova, Milena,Holy, Antonin
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p. 931 - 950
(2007/10/03)
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- Aromatic sulfonyl alpha-hydroxy hydroxamic acid compounds
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An aromatic sulfonyl alpha-hydroxy hydroxamic acid compound that, inter alia, inhibits matrix metalloprotease activity is disclosed, as is a treatment process that comprises administering a contemplated aromatic sulfonyl alpha-hydroxy hydroxamic acid comp
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- Neuromuscular blocking agents. Some approaches to short acting compounds
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A series of amidic and N-methylamidic methyl and trideuteromethyl quaternary analogues of atracurium have been prepared.All were less potent and longer acting neuromuscular blocking agents than atracurium, and all showed appreciable vagal blockade at neur
- Stenlake, J B,Dhar, N C,Haddow, J,McDonald, I M,Maehr, R B,Wastila, W B
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p. 463 - 477
(2007/10/02)
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- A SIMPLE PREPARATION OF R OR S GLYCIDIC ESTERS; APPLICATION TO THE SYNTHESIS OF ENANTIOMERICALLY PURE α-HYDROXYESTERS
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The simple preparation of enantiomerically pure α-hydroxyesters by the regioselective reaction of lithio and magnesiocuprates with glycidic esters 3 or 3' readily available from serine is described.
- Larcheveque, Marc,Petit, Yves
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p. 1993 - 1996
(2007/10/02)
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- Laboratory-Scale Enzymatic/Chemical Syntheses of D- and L-β-Chlorolactic Acid and D- and L-Potassium Glycidate
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This paper describes preparations of D- (and L-) chlorolactic acids having enantiomeric excesses greater than 97percent by D- (and L-) lactate dehydrogenase catalyzed reduction of chloropyruvic acid with NADH.In syntheses carried out on 0.1-0.5 mol scales
- Hirschbein, Bernard L.,Whitesides, George M.
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p. 4458 - 4460
(2007/10/02)
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