111058-33-4Relevant articles and documents
Total Synthesis of Solandelactone i
Eichenauer, Nils C.,Tschersich, Roxanne,Pietruszka, J?rg
, p. 2782 - 2790 (2015)
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.
Synthesis of optically active N6-alkyl derivatives of (R)-3-(adenin-9-yl)-2-hydroxypropanoic acid and related compounds
Krecmerova, Marcela,Budesinsky, Milos,Masojidkova, Milena,Holy, Antonin
, p. 931 - 950 (2003)
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.
SELECTIVE INHIBITORS OF NLRP3 INFLAMMASOME
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Paragraph 0605, (2019/02/15)
The present disclosure relates to compounds of Formula (I): (I); and to their pharmaceutically acceptable salts, pharmaceutical compositions, methods of use, and methods for their preparation. The compounds disclosed herein are useful for inhibiting the maturation of cytokines of the IL-1 family by inhibiting inflammasomes and may be used in the treatment of disorders in which inflammasome activity is implicated, such as autoinflammatory and autoimmune diseases and cancers.
Potent inhibitors of a shikimate pathway enzyme from Mycobacterium tuberculosis: Combining mechanism- and modeling-based design
Reichau, Sebastian,Jiao, Wanting,Walker, Scott R.,Hutton, Richard D.,Baker, Edward N.,Parker, Emily J.
scheme or table, p. 16197 - 16207 (2012/03/26)
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.
An efficient route to α,β-epoxy ketones of high enantiomerical purity
Pegorier,Petit,Mambu,Larcheveque
, p. 1403 - 1405 (2007/10/02)
Acylepoxides were obtained in high enantiomeric purity (ee = 92-99%) by addition of organolithium or Grignard reagents to enantiomerically pure methyl or ethyl 2,3-epoxypropanoates at low temperature (-85°C).
Preparation d'α-hydroxyesters et d'α-hydroxyaldehydes enantiomeriquement purs. Application a la synthese enantiospecifique de la pheromone sexuelle de la cochenille Pseudococcus comstocki
Larcheveque, Marc,Petit, Yves
, p. 130 - 139 (2007/10/02)
Enantiomerically pure glycidic esters may be obtained in good yields by nitrous deamination of (S) or (R) serine; 2-bromo-3-hydroxy propionic acid is obtained and cyclized with alcoholic potash to give potassium glycidate; by reacting this salt with a sulfate, a primary iodide or an active bromide in acetonitrile in the presence of 18-crown-6, various glycidic esters were prepared.The ethyl glycidate reacts with lithiocuprates (alkyl or vinyl) but also with magnesiocuprates to afford a totally regiospecific reaction with the exclusive formation of α-hydroxyesters.The reaction is also possible with acetylides but it is necessary to use aluminium acetylides.With organolithium compounds reaction with the ester function of methyl glycidate occurs, leading to the formation of α-epoxyketones.The reduction of α-hydroxyesters (as protected form) with DIBAL-H at -70 deg C affords the corresponding α-hydroxyaldehydes in nearly quantitative yields.These reactions were applied to the synthesis of (R)-(+)-2,6-dimethyl-1,5-heptadien-3-ol acetate, the sex pheromone of the Comstock Mealybug, Pseudococcus comstocki.
A SIMPLE PREPARATION OF R OR S GLYCIDIC ESTERS; APPLICATION TO THE SYNTHESIS OF ENANTIOMERICALLY PURE α-HYDROXYESTERS
Larcheveque, Marc,Petit, Yves
, p. 1993 - 1996 (2007/10/02)
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.
