3036-18-8Relevant academic research and scientific papers
Enantioselective and Diastereodivergent Synthesis of Spiroindolenines via Chiral Phosphoric Acid-Catalyzed Cycloaddition
Gandon, Vincent,Masson, Géraldine,Mati?i?, Mateja,Neuville, Luc,Van Elslande, Elsa,Varlet, Thomas
supporting information, p. 11611 - 11619 (2021/08/16)
A diastereodivergent and enantioselective synthesis of chiral spirocyclohexyl-indolenines with four contiguous stereogenic centers is achieved by a chiral phosphoric acid-catalyzed cycloaddition of 2-susbtituted 3-indolylmethanols with 1,3-dienecarbamates. Modular access to two different diastereoisomers with high enantioselectivities was obtained by careful choice of reaction conditions. Their functional group manipulation provides an efficient access to enantioenriched spirocyclohexyl-indolines and -oxindoles. The origins of this stereocontrol have been identified using DFT calculations, which reveal an unexpected mechanism compared to our previous work dealing with enecarbamates.
Stereoselective Cross-Coupling of Grignard Reagents and Conjugated Dienylbromides using Iron Salts with Magnesium Alkoxides
Chourreu, Pablo,Gayon, Eric,Guerret, Olivier,Guillonneau, Lo?c,Lefèvre, Guillaume
supporting information, p. 4701 - 4706 (2021/09/10)
A convenient procedure allowing iron-catalyzed cross-coupling of alkyl or aryl Grignard reagents and conjugated dienyl bromides is reported, relying on the use of cheap and non-toxic magnesium alkoxides as sole additives. An excellent stereoselectivity is observed in the alkyl-dienyl series. This sequence has been applied to the synthesis of the sex pheromone of codling moth, illustrating its applicability for obtaining targets of industrial interest. Preliminary mechanistic studies carried out on the aryl-dienyl cross-coupling suggest that in situ generated ate homoleptic organoiron(II) species act as catalytically relevant intermediates. A modified preparative method for the realization of THF solutions of dienyl bromides as “ready-to-use” coupling partners is also discussed, circumventing the thermal instability of those derivatives.
Reconstitution of a Type II Polyketide Synthase that Catalyzes Polyene Formation
Du, Danyao,Katsuyama, Yohei,Shin-ya, Kazuo,Ohnishi, Yasuo
, p. 1954 - 1957 (2018/02/10)
While type II polyketide synthases (PKSs) are known for producing aromatic compounds, a phylogenetically new subfamily of type II PKSs have been recently proposed to synthesize polyene structures. Here we report in vitro analysis of such a type II PKS, IgaPKS for ishigamide biosynthesis. The ketoreductase (Iga13) and dehydratase (Iga16) were shown to catalyze the reduction of a β-keto group and dehydration of a β-hydroxy group, respectively, to form a trans double bond. Incubation of the acyl carrier protein (Iga10), the ketosynthase/chain length factor complex (Iga11–Iga12), Iga13 and Iga16 with malonyl and hexanoyl-CoAs and NADPH followed by KOH hydrolysis resulted in the formation of four unsaturated carboxylic acids (C8, C10, C12, and C14), indicating that IgaPKS catalyzes tetraene formation by repeating the cycle of condensation, keto-reduction and dehydration with strict stereo-specificity. We propose “highly reducing type II PKS subfamily” for the polyene-producing type II PKSs.
CDP-Ethanolamine and CDP-Choline: One-pot synthesis and 31P NMR study
Ghezal, Salma,Thomasson, Maggie S.,Lefebvre-Tournier, Isabelle,Périgaud, Christian,Macnaughtan, Megan A.,Roy, Béatrice
supporting information, p. 5306 - 5310 (2015/01/16)
Herein we report a one-pot multi-step synthesis of the cofactors CDP-Ethanolamine and CDP-Choline starting from cytidine 5′-monophosphate and using commercially available and/or easily prepared reagents. While studying the 31P NMR spectrum of CDP-Ethanolamine, an unexpected characteristic for a pyrophosphate diester was observed as it showed a singlet or two doublets depending upon the pH. Therefore, further NMR studies were undertaken to investigate the pH dependence of the peak splitting pattern and measure the acid dissociation constants of the compounds.
Teratogenic effects of diatom metabolites on sea urchin Paracentrotus lividus embryos
Romano, Giovanna,Miralto, Antonio,Ianora, Adrianna
experimental part, p. 950 - 967 (2010/12/18)
The diatom-derived polyunsaturated aldehydes (PUAs), 2-trans,4-trans- decadienal, 2-trans,4-trans-octadienal, 2-trans,4-trans,7-octatrienal, 2-trans,4-trans-heptadienal, as well as tridecanal were tested on early and later larval development in the sea urchin Paracentrotus lividus. We also tested the effect of some of the more abundant diatom polyunsaturated fatty acids (PUFAs) on development, in particular 5,8,11,14,17-eicosapentaenoic acid (EPA), one of the main precursors of diatom PUAs, as well as 4,7,10,13,16,19- docosahexaenoic acid (DHA), 6,9,12,15-octadecatetraenoic acid (stearidonic acid), 6,9,12-octadecatrienoic acid (γ-linolenic acid) and 9,12-octadecadienoic acid (linoleic acid). PUAs blocked sea urchin cell cleavage in a dose dependent manner and with increasing chain length from C7 to C10 PUAs, with arrest occurring at 27.27 μM with heptadienal, 16.13 μM with octadienal, 11.47 μM with octatrienal and 5.26 μM with decadienal. Of the PUFAs tested, only EPA and stearidonic acid blocked cleavage, but at much higher concentrations compared to PUAs (331 μM for EPA and 181 μM for stearidonic acid). Sub-lethal concentrations of decadienal (1.32-5.26 μM) delayed development of embryos and larvae which showed various degrees of malformations depending on the concentrations tested. Sub-lethal concentrations also increased the proportion of TUNEL-positive cells indicating imminent death in embryos and larvae. Using decadienal as a model PUA, we show that this aldehyde can be detected spectrophotometrically for up to 14 days in f/2 medium.
Evidence from Raman spectroscopy that InhA, the mycobacterial enoyl reductase, modulates the conformation of the NADH cofactor to promote catalysis
Bell, Alasdair F.,Stratton, Christopher F.,Zhang, Xujie,Novichenok, Polina,Jaye, Andrew A.,Nair, Pravin A.,Parikh, Sapan,Rawat, Richa,Tonge, Peter J.
, p. 6425 - 6431 (2008/02/09)
InhA, the enoyl reductase from Mycobacterium tuberculosis, catalyzes the NADH-dependent reduction of trans-2-enoyl-ACPs. In the present work, Raman spectroscopy has been used to identify catalytically relevant changes in the conformation of the nicotinamide ring that occur when NADH binds to InhA. For 4(S)-NADD, there is an 11 cm-1 decrease in the wavenumber of the C4-D stretching band (νC-D) and a 50% decrease in the width of this band upon binding to InhA. While a similar reduction in line width is observed for the corresponding band arising from 4(R)-NADD, νC-D for this isomer increases 34 cm-1 upon binding to InhA. These changes in νC-D indicate that the nicotinamide ring adopts a bound conformation in which the 4(S)C-D bond is in a pseudoaxial orientation. Mutagenesis of F149, a conserved active site residue close to the cofactor, demonstrates that this enzyme-induced modulation in cofactor structure is directly linked to catalysis. In contrast to the wild-type enzyme, Raman spectra of NADD bound to F149A InhA resemble those of NADD in solution. Consequently, F149A is no longer able to optimally position the cofactor for hydride transfer, which correlates with the 30-fold decrease in feat and 2-fold increase in D(V/KNADH) caused by this mutation. These studies thus substantiate the proposal that hydride transfer is promoted by pseudoaxial positioning of the NADH pro-4S bond, and indicate that catalysis of substrate reduction by InhA results, in part, from correct orientation of the cofactor in the ground state.
A synthetic approach to natural dienamides of insecticidal interest
Abarbri, Mohamed,Parrain, Jean-Luc,Duchene, Alain
, p. 239 - 249 (2007/10/03)
An efficient synthesis of dienamides of insecticidal interest has been stereoselectively achieved featuring a Stille cross-coupling reaction as the key step.
Ene Reaction of Pummerer-Type Reaction Intermediate and Synthesis of Pellitorine
Lin, Wei-Shing,Wang, Huey-Min,Chen, Ling-Ching
, p. 159 - 161 (2007/10/03)
Pummerer-type reaction intermediate 2 of α-(methylthio)acetic acid (1) has been found to react with 1-alkenes to afford ene adducts 3. Pellitorine S was synthesized from the adduct 3d.
Expedient synthesis of unsaturated amide alkaloids from Piper spp: Exploring the scope of recent methodology
Strunz, George M.,Finlay, Heather J.
, p. 419 - 432 (2007/10/03)
The Sakai aryl aldehyde - cyclic ketone aldol - Grob fragmentation sequence was extended to cinnamaldehyde and cyclohexanone, and the product was elaborated to analogues of the alkaloid piperstachine. The effects of substituents on the reaction involving cinnamaldehyde were studied. The aldol-fragmentation sequence failed with benzaldehyde when cyclooctanone or cyclobutanone was substituted for cyclohexanone or cyclopentanone, and the reasons for this failure were examined. Four-carbon Wittig homologation of the piperonal-cyclobutanone aldol-fragmentation product, a hypothetical route to alkaloids such as retrofractamide A, was thus not viable. Instead, three-carbon homologation of the readily available piperonal-cyclopentanone product, using alkyne chemistry recently disclosed by Lu and Trost, afforded these alkaloids in excellent overall yield. The alkyne isomerization was also used to effect efficient syntheses of pellitorine and several other non-aromatic 2E,4E-dienoic Piper amide alkaloids. The Sakai aryl aldehyde - cyclic ketone aldol - Grob fragmentation sequence was extended to cinnamaldehyde and cyclohexanone, and the product was elaborated to analogues of the alkaloid piperstachine. The effects of substitutents on the reaction involving cinnamaldehyde were studied. The aldol-fragmentation sequence failed with benzaldehyde when cyclooctanone or cyclobutanone was substituted for cyclohexanone or cyclopentanone, and the reasons for this failure were examined. Four-carbon Wittig homologation of the piperonal-cyclobutanone aldol-fragmentation product, a hypothetical route to alkaloids such as retrofractamide A, was thus not viable. Instead, three-carbon homologation of the readily available piperonal-cyclopentanone product, using alkyne chemistry recently disclosed by Lu and Trost, afforded these alkaloids in excellent overall yield. The alkyne isomerization was also used to effect efficient syntheses of pellitorine and several other non-aromatic 2E,4E-dienoic Piper amide alkaloids.
Efficient Synthesis of Conjugated (2E)- or (2Z)-En-4-ynoic Acids and (2E,4E)- or (2Z,4E)-Dienoic Acids via Palladium-Catalysed Cross Coupling
Abarbri, Mohamed,Parrain, Jean-Luc,Cintrat, Jean-Christophe,Duchene, Alain
, p. 82 - 86 (2007/10/03)
(E)- or (Z)-Enynoic acids and (2E,4E)- or (2Z,4E)-dienoic acids can be obtained in good yields under mild conditions through palladium-catalysed cross coupling of (E)- or (2)-3-iodoprop-2-enoic acid with alkynylzinc or vinyltin reagents.
