Academic literature on the topic 'Succinates chiraux'

Abstract Numerous organic transformations are based on the use of stoichiometric amounts of phosphorus reagents. The formation of phosphane oxides from phosphanes is usually the thermodynamic driving force for these reactions. The stoichiometric amounts of phosphane oxide which are formed as by-products often significantly hamper the product purification. Organophosphorus catalysis based on P(III)/P(V) redox cycling aims to address these problems. Herein we present our recent advances in developing catalytic Wittig-type reactions. More specifically, we reported our results on catalytic Wittig reactions based on readily available Bu3P=O as pre-catalyst as well as the first microwave-assisted version of this reaction and the first enantioselective catalytic Wittig reaction utilizing chiral phosphane catalysts. Further developments led to the implementation of catalytic base-free Wittig reactions yielding highly functionalized alkylidene and arylidene succinates.

Abstract Background Direct measurement of the bioavailable α-tocopherol content presents a significant analytical challenge and requires chiral separation of the α-tocopherol stereoisomers. Objective The objective of the study was to validate an analytical method for the analysis of α-tocopherol stereoisomers in infant formulas and dairy products. Method Samples were saponified at elevated temperature and lipophilic components were extracted into an organic solvent, with subsequent chromatographic separation of the α-tocopherol stereoisomers achieved by HPLC with a chiral column and fluorescence detection. Results The method was shown to be accurate, with spike recoveries of 91.9–108.8% for RRR-α-tocopherol and 90.1–104.7% for α-tocopherol, with no statistical bias against NIST 1849a certified reference material (P-value = 0.54) and an HPLC-UV analytical method (P-value = 0.48). Acceptable precision was confirmed, with repeatabilities estimated at 3.5% RSDr (HorRat = 0.6) for RRR-α-tocopherol and 4.6% RSDr (HorRat = 0.4) for α-tocopherol. Conclusions A straightforward chiral chromatographic method for the analysis of stereoisomeric forms of α-tocopherol is described. In a single analytical run, the method can quantify: (i) the total α-tocopherol content; (ii) the nutritionally important RRR-α-tocopherol and/or 2 R, 4′-ambo, 8′-ambo-α-tocopherol contents; (iii) the amount of all-rac-α-tocopherol, all-rac-α-tocopheryl acetate, or all-rac-α-tocopheryl succinate fortified into the product. Highlights An accurate and precise chiral chromatographic method for the analysis of isomeric forms of α-tocopherol is described. The method is able to distinguish between natural and synthetic tocopherol sources. The method is accurate and precise and is suitable either for routine product compliance testing during product manufacture or as a possible reference method.

ABSTRACT Given its availability and low price, glycerol has become an ideal feedstock for the production of fuels and chemicals. We recently reported the pathways mediating the metabolism of glycerol in Escherichia coli under anaerobic and microaerobic conditions. In this work, we engineer E. coli for the efficient conversion of glycerol to d-lactic acid (d-lactate), a negligible product of glycerol metabolism in wild-type strains. A homofermentative route for d-lactate production was engineered by overexpressing pathways involved in the conversion of glycerol to this product and blocking those leading to the synthesis of competing by-products. The former included the overexpression of the enzymes involved in the conversion of glycerol to glycolytic intermediates (GlpK-GlpD and GldA-DHAK pathways) and the synthesis of d-lactate from pyruvate (d-lactate dehydrogenase). On the other hand, the synthesis of succinate, acetate, and ethanol was minimized through two strategies: (i) inactivation of pyruvate-formate lyase (ΔpflB) and fumarate reductase (ΔfrdA) (strain LA01) and (ii) inactivation of fumarate reductase (ΔfrdA), phosphate acetyltransferase (Δpta), and alcohol/acetaldehyde dehydrogenase (ΔadhE) (strain LA02). A mutation that blocked the aerobic d-lactate dehydrogenase (Δdld) also was introduced in both LA01 and LA02 to prevent the utilization of d-lactate. The most efficient strain (LA02Δdld, with GlpK-GlpD overexpressed) produced 32 g/liter of d-lactate from 40 g/liter of glycerol at a yield of 85% of the theoretical maximum and with a chiral purity higher than 99.9%. This strain exhibited maximum volumetric and specific productivities for d-lactate production of 1.5 g/liter/h and 1.25 g/g cell mass/h, respectively. The engineered homolactic route generates 1 to 2 mol of ATP per mol of d-lactate and is redox balanced, thus representing a viable metabolic pathway.

The objective is to prepare extended release micro-pellets of the s-Metoprolol Succinate which is chirally pure molecules. Commercially Metoprolol Succinate is available the racemic mixture of the s and r isomers. Out of both the isomers s-isomer is predominantly responsible for the cardiac beta blocking activity. So to use the more desirable beta blocking activity of s-Metoprolol Succinate, extended release micro-pellets of the s-Metoprolol Succinate was prepared. Due to pure chiral molecules the dose was also reduced to half to that of the racemic mixture. Extended release micro-pellets of the s-Metoprolol Succinate was prepared by the fluid bed technology, in which s-Metoprolol Succinate along with binder and anti-adherent material was sprayed on the inert core. These drug loaded pellets of the s-Metoprolol Succinate was than coated with ethyl cellulose as extended release polymer, hypromellose as pore former and acetyl tri butyl as novel plasticizer and talc as an anti-adherent. The formulation was further optimized for drug release, as per USP recommended dissolution condition, using central composite design (CC). Results shows that at level of 58-66% w/w extended release coating with any studied concentration of acetyl tri butyl citrate and hypromellose gives desired drug release profile.

Cette thèse décrit une voie d'accès aux cyclopropanols chiraux et en étudie les potentialités synthétiques. Préparé à partir du méthyl-2 succinate de n-butyle, l'hydroxy-1 méthyl-2 cyclopropanecarboxaldéhyde est un précurseur de (vinylcarbinol)-1 cyclopropanols lesquels, subissent en milieu acide soit une extension de cycle C3→C4 régiospécifique en vinyl-2 cyclobutanones (BF3-Et20), soit une extension de cycle C3→C4→C5 en cyclopentène-2 ones (CH3S03H-P205). La réaction thermique des méthyl-2 vinylcyclopropanes donne par ène-réaction des produits d'ouverture de cycle limitant l'intérêt du réarrangement vinylcyclopropane-cyclopentène ; ce problème est contourné par cette nouvelle approche. Les (R)(+) et (S)(-) méthyl-2 succinates de méthyle, préparés par résolution enzymatique à l'aide de la lipase du pancréas de porc, sont cyclisés par réaction du type acyloïne en (R) et (S) méthyl-3 disiloxycyclobutènes respectivement. Ceux-ci par régression de cycle stéréosélective C4 → C3 en milieu basique, donnent accès sans altération du centre chiral à des hydroxy-1 cyclopropanecarbo­ xaldéhydes, utilisés pour préparer des (vinylcarbinol)-1 cyclopropanols optiquement actifs. Une extension de cycle C3→C4 régio- et stéréospécifique conduit alors aux vinyl-2 cyclobutanones avec une très bonne énantiosélectivité. Ces composés ont été utilisés pour préparer la (S)(+) méthyl-5 cyclohexène-2-one et un buténolide : la quercus lactone b. Les vinyl-2 cyclobutanones sont des précurseurs de cycle en C5, C6 et C8, cette méthodologie, ne mettant pas en jeu d'ions cyclopropylcarbinyl vrais comme le prouve la stéréospécificité des réarrangements, permet donc, à partir de succinates chiraux, d'envisager la synthèse totale de produits naturels de structures variées
The aim of this thesis is the preparation and study of the synthetic potential of chiral cyclopropanols. The 1-hydroxy 2-methyl cyclopropanecarboxaldehyde available from 2-methylsuccinate, is used to prepare 1-(vinylcarbinol} cyclopropanols which, undergo acid induced C3 C4 regiospecific ring expansion into 2-vinyl cyclobutanones (BF3-Et20) or C3 -+ C4 --+- C5 ring expansion into cyclopenten-2- ones (CH3S03H-P205). The thermal rearrangement of 2-methyl vinylcyclopropanes leads by an ene-reaction to ring-opened products ; therefore the limitation of the thermal vinylcyclopropane-cyclopentene ring enlargement is removed by this new approach. (R)(+) and (S)(-). Dimethyl 2-methylsuccinates, now available from enantiose­ lective hydrolysis by porcine pancreatic lipase, undergo acyloin type cyclization into (R) and (S) 3-methyl-1,2-disiloxycyclobutene, respectively. Base-induced stereoselective C4 C3 ring contraction of these cyclobutenes provides 1-hydroxycyclopropanecarboxaldehydes which are used to prepare optically active 1-alkenylcyclopropanols. Then, acid-induced regio- and stereospecific C3---+ C4 ring enlargement leads to 2-vinylcyclobutanones with high enantiomeric excesses. These compounds are used to synthetize (S) 5-methyl cyclohexen-2-one and abutenolide ; i. E. The quercus lactone b2-Vinylcyclobutanones are efficient precursors of 5-, 6- and 8-membered rings. Therefore, this new methodology, which does not involve cyclopropylcarbiny1 cations as proven by the stereospecificity of the rearrangements, allows one to prepare from chiral succinates natural compounds bearing different frameworks

Unsaturated half acid esters such as 1 are readily prepared by Stobbe condensation between dialkyl succinate and an aldehyde. Johannes G. de Vries of DSM and Floris P. J. T. Rutjes of Radboud University Nijmegen observed (Adv. Synth. Catal. 2008, 350, 85) that these acids were excellent substrates for enantioselective hydrogenation. Kazuaki Kudo of the University of Tokyo designed (Organic Lett. 2008, 10, 2035) a resin bound peptide catalyst for the transfer reduction of unsaturated aldehydes such as 3 , using 4 as the net H2 donor. Note that 5 was produced with high enantiocontrol from 3 that was a ~ 2:1 mixture of geometric isomers. Motomu Kanai and Masakatsu Shibasaki of the University of Tokyo devised (J. Am. Chem. Soc. 2008, 130, 6072) a chiral Gd catalyst that mediated the conjugate cyanation of enones such as 6 with high ee. Eric N. Jacobsen of Harvard University prepared (Angew. Chem. Int. Ed. 2008, 47, 1762) a dimeric Al salen catalyst that showed improved activity over the monomeric catalysts. Even congested imides such as 8 could be cyanated efficiently, delivering alkylated quaternary stereogenic centers. Takahiro Nishimura and Tamio Hayashi of Kyoto University optimized (J. Am. Chem. Soc. 2008, 130, 1576) the Rh*-catalyzed enantioselective conjugate addition of silyl acetylenes to enones such as 10, to give 12. Adriaan J. Minnaard and Ben L. Feringa of the University of Groningen devised (Angew. Chem. Int. Ed. 2008, 47, 398) conditions for the enantioselective 1,6-conjugate addition of alkyl Grignard reagents to diene esters such as the inexpensive ethyl sorbate 14. The product 16 incorporated, in addition to the newly formed stereogenic center, a geometrically defined E alkene. William S. Bechara and André B. Charette of the Université de Montréal found (Organic Lett. 2008, 10, 2315) that alkyl Grignard reagents could be induced to add with high enantioselectivity to pyridyl sulfones such as 17. In a different approach, Gregory C. Fu of MIT developed (J. Am. Chem. Soc. 2008, 130, 3302; J. Am. Chem. Soc. 2008, 130, 2756) conditions for the enantioselective alkenylation of racemic bromo esters such as 19, The latter reference is to the analogous enantioselective coupling of organozinc bromides with racemic allylic chlorides.