- REACTION OF ORGANOCADMIUM REAGENTS WITH ETHYL CYANOFORMATE: PREPARATION OF α-KETO ESTERS
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Organocadmium reagents reacted with the cyano-function of ethyl cyanoformate in the presence of ZnCl2 to afford the corresponding α-keto esters.
- Akiyama, Yasunobu,Kawasaki, Tomomi,Sakamoto, Masanori
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- A convenient preparation of α-keto esters by the Grignard reaction on N-acylpyrazoles
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The α-keto esters were prepared by the formation of N-acylpyrazole followed by the appropriate Grignard reaction. These short step reaction conveniently afforded various α-keto esters in good yields.
- Kashima, Choji,Shirahata, Yoshie,Tsukamoto, Yoshihiro
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- Biocatalytic Construction of Quaternary Centers by Aldol Addition of 3,3-Disubstituted 2-Oxoacid Derivatives to Aldehydes
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The congested nature of quaternary carbons hinders their preparation, most notably when stereocontrol is required. Here we report a biocatalytic method for the creation of quaternary carbon centers with broad substrate scope, leading to different compound classes bearing this structural feature. The key step comprises the aldol addition of 3,3-disubstituted 2-oxoacids to aldehydes catalyzed by metal dependent 3-methyl-2-oxobutanoate hydroxymethyltransferase from E. coli (KPHMT) and variants thereof. The 3,3,3-trisubstituted 2-oxoacids thus produced were converted into 2-oxolactones and 3-hydroxy acids and directly to ulosonic acid derivatives, all bearing gem-dialkyl, gem-cycloalkyl, and spirocyclic quaternary centers. In addition, some of these reactions use a single enantiomer from racemic nucleophiles to afford stereopure quaternary carbons. The notable substrate tolerance and stereocontrol of these enzymes are indicative of their potential for the synthesis of structurally intricate molecules.
- Marín-Valls, Roser,Hernández, Karel,Bolte, Michael,Parella, Teodor,Joglar, Jesús,Bujons, Jordi,Clapés, Pere
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supporting information
p. 19754 - 19762
(2020/12/01)
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- Domino Synthesis of α,β-Unsaturated γ-Lactams by Stereoselective Amination of α-Tertiary Allylic Alcohols
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Tertiary allylic alcohols equipped with a carboxyl group can be smoothly aminated under ambient conditions by a conceptually new and stereoselective protocol under palladium catalysis. The in situ formed Z-configured γ-amino acid cyclizes to afford an α,β-unsaturated γ-lactam, releasing water as the only byproduct. This practical catalytic transformation highlights the use of a carboxyl group acting as an activating and stereodirecting functional group to provide a wide series of pharma-relevant building blocks. Various control reactions support the crucial role of the carboxyl group in the substrate to mediate these transformations.
- Xie, Jianing,Xue, Sijing,Escudero-Adán, Eduardo C.,Kleij, Arjan W.
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p. 16727 - 16731
(2018/11/23)
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- Switchable C-H Functionalization of N-Tosyl Acrylamides with Acryloylsilanes
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A controllable Rh-catalyzed protocol to access alkylation and alkenylation-annulation of N-tosyl acrylamide with acryloyl silane is reported. In contrast to the directing group or catalyst-dependent divergent sp2 C-H alkylation/alkenylation, the intrinsic property of acryloylsilane allows the switchable reaction manifold, thereby affording either alkylation or annulation products with slight modification of the reaction conditions.
- Song, Shengjin,Lu, Ping,Liu, Huan,Cai, Sai-Hu,Feng, Chao,Loh, Teck-Peng
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supporting information
p. 2869 - 2872
(2017/06/13)
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- SYNTHESIS METHOD FOR L-CYCLIC ALKYL AMINO ACID AND PHARMACEUTICAL COMPOSITION HAVING THEREOF
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A synthesis method for L-cyclic alkyl amino acid and a pharmaceutical composition having the said amino acid are provide in the present disclosure provides. The synthesis method comprises: step A.) preparing a cyclic alkyl keto acid or a cyclic alkyl keto acid salt having Structural Formula (I) or Structural Formula (II), and step B.) mixing the cyclic alkyl keto acid or the cyclic alkyl keto acid salt with ammonium formate, a leucine dehydrogenase, a formate dehydrogenase and a coenzyme NAD+, and carrying out a reductive amination reaction to generate the L-cyclic alkyl amino acid, wherein the Structural Formula (I) is where n1≧1, m1≧0 and the M1 is H or a monovalent cation; the Structural Formula (II) is where n2≧0, m2≧0, the M2 is H or a monovalent cation, an amino acid sequence of the leucine dehydrogenase is SEQ ID No.1.
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- Catalytic formal cycloadditions between anhydrides and ketones: Excellent enantio and diastereocontrol, controllable decarboxylation and the formation of adjacent quaternary stereocentres
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It has been shown for the first time that enolisable anhydrides can participate in highly efficient and diastereo/enantioselective additions to activated ketones. In these reactions the anhydride component formally acts (initially) as the nucleophilic component. These processes are promoted by novel, readily prepared urea-substituted cinchona alkaloid-derived catalysts at low loadings under mild conditions. Three classes of enolisable anhydride and three different types of activated ketone were shown to be compatible with the process-generating a diverse range of structurally distinct and densely functionalised lactone products with the formation of two new stereocentres, one of which is quaternary. In one example, a product incorporating two contiguous quaternary stereocentres (one all carbon) was formed with outstanding enantiocontrol. It has been shown in the case of glutaconic anhydride derivatives that the cycloaddtion process is reversible, and can be accompanied by decarboxylation and olefin isomerisation. Reaction conditions can be modified to give access to three types of product with good-excellent ee.
- Cornaggia, Claudio,Gundala, Sivaji,Manoni, Francesco,Gopalasetty, Nagaraju,Connon, Stephen J.
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supporting information
p. 3040 - 3046
(2016/03/19)
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- As opioid receptor antagonists or inverse agonists of the novel compounds
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Novel compounds which are antagonists or inverse agonists at one or more of the opioid receptors, pharmaceutical compositions containing them, to processes for their preparation.
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Paragraph 0272-0274
(2016/10/08)
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- Rhodium(iii)-catalyzed C-H allylation of electron-deficient alkenes with allyl acetates
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Rhodium-catalyzed C-H allylation of acrylamides with allyl acetates is reported. The use of weakly coordinating directing group resulted in high reaction efficiency, broad functionality tolerance and excellent γ-selectivity, which opens a new synthetic pathway for the access of 1,4-diene skeletons.
- Feng, Chao,Feng, Daming,Loh, Teck-Peng
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supporting information
p. 342 - 345
(2015/01/09)
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- SOLUBLE GUANYLATE CYCLASE ACTIVATORS
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A compound of Formula I or a pharmaceutically acceptable salt thereof, are capable of modulating the body's production of cyclic guanosine monophosphate (" cGMP") and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The invention furthermore relates to processes for preparing compounds of Formula I, or a pharmaceuticall acceptable salt thereof, for their use in the therapy and prophylaxis of the abovementioned diseases and for preparing pharmaceuticals for this purpose, and to pharmaceutical preparations which comprise compounds of Formula I or a pharmaceutically acceptable salt thereof.
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Page/Page column 38; 39
(2015/06/25)
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- Room-Temperature Decarboxylative Couplings of α-Oxocarboxylates with Aryl Halides by Merging Photoredox with Palladium Catalysis
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Enabled by merging iridium photoredox catalysis and palladium catalysis, α-oxocarboxylate salts can be decarboxylatively coupled with aryl halides to generate aromatic ketones and amides at room temperature. DFT calculations suggest that this reaction proceeds through a Pd0-PdII-PdIII pathway, in which the PdIII intermediate is responsible for reoxidizing IrII to complete the IrIII-IrIII-IrII photoredox cycle. Like a mergin': Enabled by merging iridium photoredox catalysis and palladium catalysis, palladium-catalyzed decarboxylative coupling of α-oxocarboxylates with aryl halides can proceed at room temperature. DFT calculations suggest that a Pd0-PdII-PdIII catalytic cycle is merged with an IrIII-IrIII-IrII photoredox cycle, in which PdIII is responsible for oxidizing IrII to complete the photoredox cycle.
- Cheng, Wan-Min,Shang, Rui,Yu, Hai-Zhu,Fu, Yao
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supporting information
p. 13191 - 13195
(2015/09/15)
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- Rhodium(III)-catalyzed olefinic C-H alkynylation of acrylamides using tosyl-imide as directing group
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The Rh(III)-catalyzed C-H alkynylation of acrylamide derivative is realized using a hypervalent alkynyl iodine reagent. The use of a weakly coordinating directing group proved to be of critical importance. This reaction displays broad functional group tolerance and high efficiency, which opens a new synthetic pathway to access functionalized 1,3-enyne skeletons.
- Feng, Chao,Feng, Daming,Luo, Yang,Loh, Teck-Peng
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supporting information
p. 5956 - 5959
(2015/01/08)
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- Peptide-catalyzed stereoselective conjugate addition reactions generating all-carbon quaternary stereogenic Centers
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A powerful catalyst: Quaternary stereogenic centers adjacent to tertiary stereocenters were formed with high diastereoselectivities and enantioselectivities in conjugate addition reactions between aldehydes and β,β-disubstituted nitroolefins by using a peptidic catalyst (see scheme). γ-Amino acids and heterocyclic compounds bearing quaternary stereogenic centers are easily accessible from the products. Copyright
- Kastl, Robert,Wennemers, Helma
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supporting information
p. 7228 - 7232
(2013/07/26)
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- Chiral-at-metal octahedral iridium catalyst for the asymmetric construction of an all-carbon quaternary stereocenter
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Metal-templated organocatalysis: The enantioselective formation of an all-carbon quaternary stereocenter is catalyzed by the ligand sphere of an inert bis-cyclometalated iridium complex (see picture). In this complex, the metal-centered chirality serves as the sole source for the effective asymmetric induction. Copyright
- Chen, Liang-An,Tang, Xiaojuan,Xi, Jianwei,Xu, Weici,Gong, Lei,Meggers, Eric
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supporting information
p. 14021 - 14025
(2014/01/06)
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- Directing-group-assisted copper-catalyzed olefinic trifluoromethylation of electron-deficient alkenes
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Assistance provided: The directing group in the title reaction not only activates the substrates but also allows the stereospecific formation of cis-trifluoromethylated products. The reaction is operationally simple and tolerates a wide variety of functional groups, thus providing an efficient method for the stereoselective synthesis of β-CF3-functionalized acrylamide derivatives. Copyright
- Feng, Chao,Loh, Teck-Peng
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supporting information
p. 122414 - 122417
(2013/12/04)
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- Catalytic enantioselective protonation of α-oxygenated ester enolates prepared through phospha-brook rearrangement
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(Chemical Equation Presented) Phosphonates go chiral: The organocatalytic enantioselective reaction of α-ketoesters with phosphites using cinchona alkaloids and Na2CO3 has afforded α-phosphonyloxy esters with high enantioselectivities (see scheme). This process allows the formation of both enantiomers of the product. A catalyst loading of as low as 2 mol% does not result in a significant decrease of the enantioselectivity.
- Hayashi, Masashi,Nakamura, Shuichi
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supporting information; experimental part
p. 2249 - 2252
(2011/04/16)
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- NOVEL COMPOUNDS AS ANTAGONISTS OR INVERSE AGONISTS AT OPIOID RECEPTORS
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Novel compounds which are antagonists or inverse agonists at one or more of the opioid receptors, pharmaceutical compositions containing them, to processes for their preparation.
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- METHOD OF TREATMENT USING NOVEL ANTAGONISTS OR INVERSE AGONISTS AT OPIOID RECEPTORS
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A method of treatment using pharmaceutical compositions containing novel antagonists or inverse agonists at opioid receptors for the treatment of binge eating disorder, anorexia nervosa, bulimia nervosa, excess drug or alcohol use, or eating disorder not otherwise specified.
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- CALCIUM ION CHANNEL MODULATORS and USES THEREOF
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Compounds of formula (I), wherein R1 is hydrogen, hydroxyl or aralkyl; R2 is an optionally substituted alkyl, aryl or heteroaryl (said substituents are selected from hydroxyl, alkoxyl, haloalkoxyl, aryl, heteroaryl, cycloalkyl, amino, monoalkylamino, dialkylamino, alkylsulphonyl, alkylsulphinyl, alkylsulphonylamino, acylamino, saturated or partially unsaturated heterocyclic groups and groups of formula COY); W is selected from oxygen, sulphur, groups of formula NR7, wherein R7 is hydrogen, alkyl, aryl or heteroaryl and groups of formula CR8R9, wherein R8 and R9 are hydrogen, alkyl, aryl or heteroaryl; and X is selected from nitrogen and groups of formula CR10, wherein R10 is hydrogen, alkyl, aryl, heteroaryl, halogen or haloalkyl, inhibit the interaction between Cavx channels and Cavβ proteins and are of use in the treatment and prevention of a number of diseases and conditions including pain and lower urinary tract disorders.
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Page/Page column 103-104
(2010/04/27)
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- Non-steroidal progesterone receptor modulators
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The present invention relates to non-steroidal progesterone receptor modulators of the general formula I, the use of the progesterone receptor modulators for the manufacture of medicaments, and pharmaceutical compositions which comprise these compounds. The compounds according to the invention are suitable for the therapy and prophylaxis of gynecological disorders such as endometriosis, leiomyomas of the uterus, dysfunctional bleeding and dysmenorrhoea, and for the therapy and prophylaxis of hormone-dependent tumours and for use for female fertility control and for hormone replacement therapy.
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Page/Page column 211
(2009/10/31)
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- INDOLE- 3 -GLYOXYLAMIDE DERIVATIVES FOR USE AS CALCIUM ION CHANNEL MODULATORS
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Compounds of formula (I) are of use in treating a range of conditions, including pain.
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Page/Page column 76-77
(2009/12/05)
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- Synthesis and reactivity of α and β-chloro-α-phenylselanyl esters
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Thermal decomposition of the dichloro-adducts derived from α-phenylselanylesters 1, 2 and 4 has been studied. N-Chloro-succinimide treatment of esters 2 was an efficient preparative method for α-chloro-α-phenylselanylesters 10 and α-chloro-α,β-unsaturated esters 11. Some transformations of esters 10 were achieved, α,β-Dichloro-α-phenylselanylesters 22 were prepared from β-chloro-α-phenylselanylesters 5 or by decomposition of the dichloroselenuranes 21 derived from esters 4. (C) 2000 Elsevier Science Ltd.
- Lebarillier, Loic,Outurquin, Francis,Paulmier, Claude
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p. 7495 - 7502
(2007/10/03)
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- Controlled release of perfumery aldehydes and ketones by Norrish type-II photofragmentation of α-keto esters in undegassed solution
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Alkyl or aryl α-keto esters of primary or secondary alcohols decompose upon irradiation at 350-370 nm from the intermediate triplet state into aldehydes or ketones in polar, as well as apolar solvents. The use of these keto esters as delivery systems for the controlled release of perfumery aldehydes and ketones was investigated by photoirradiation in the presence of oxygen with a Xe or UV lamp, as well as outdoor sunlight. Systematic GC/MS analysis of the irradiated solutions showed that, under these conditions, the desired Norrish type-II fragmentation of the ester side chain is the predominant reaction pathway in most of the cases. γ-H Abstraction from the alkyl side chain of alkyl keto esters, as well as an intramolecular Paterno- Buchi reaction or epoxidation of the alkene function in different citronellyl α-keto esters were identified as the most important side reactions. Some of the experimental findings have been rationalized on the basis of ab initio and density-functional calculations. (Cyclohexyl)oxoacetates and oxo(phenyl)acetates were found to be the most suitable precursors for the desired perfumery applications.
- Rochat, Sabine,Minardi, Caroline,De Saint Laumer, Jean-Yves,Herrmann, Andreas
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p. 1645 - 1671
(2007/10/03)
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- Asymmetric grignard synthesis with cyclic 1,2 aminoalcohols
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Processes for preparing a single enantiomer of an alpha , alpha -disubstituted- alpha -hydroxy acetic acid, especially cyclohexylphenylglycolic acid (CHPGA), is disclosed. The processes employ cyclic 1,2-aminoalcohols as chiral auxiliaries by forming diastereomeric esters of aminoalcohols or diastereomeric amides of oxazolidines. Intermediates useful in the process are also disclosed.
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- Rigid aminoalcohol backbone as a highly defined chiral template for the preparation of optically active tertiary α-hydroxyl acids
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Constrained aminoalcohol derived-ketoester or amides have provided a new entry for the production of enantiopure acid 1 for (S)-oxybutynin.
- Senanayake, Chris H.,Fang, Kevin,Grover, Paul,Bakale, Roger P.,Vandenbossche, Charles P.,Wald, Stephen A.
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p. 819 - 822
(2007/10/03)
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- Synthesis and reactivity of β-phenylselanyl α-oxoesters
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β-Phenylsetanyl α-oxoesters 2 were prepared by N-phenylselanyl morpholine treatment of α-oxoesters 1, oxidized into β-unsaturated α- oxoesters 5 and subjected to the Wittig-Horner olefination. The diethyl (l- phenylselanylalkyl)maleates 6 have led, after [2,3]sigmatropic rearrangement of the corrsponding selenoxides to the diethyl 3-alkylidene-2- hydroxysuccinates 7. The 2-(1-butoxycarbonylamino)-3-alkylidenesuccinates 8 were prepared in a similar way. The decomposition of halo-adducts derived from components 6 has the synthesis of the siethyl 3-alkylidene-2- halosuccinates 9 and 10.
- Boivin, Stephane,Outurquin, Francis,Paulmier, Claude
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p. 16767 - 16782
(2007/10/03)
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- Studies on Conjugated Nitriles. IV. Reaction of Ethyl Cyanoformate with Organomagnesium, -zinc, and - cadmium Reagents, and Phosphonium Ylide
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The reaction of ethyl cyanoformate (1a) with phenylcadmium bromide (3a) gave ethyl benzoate (4), ethyl 2-phenyl-2-oxoacetate (5a), and 2-ethoxycarbonyl-2,4-diphenyl-3-imidazoline-5-one (6).In the presence of zinc chloride, the addition of 3a to the cyano group of 1a occured to give only 5a.The similar reaction of 1a with other organocadmium reagents (3b-f) in the presence of zinc chloride gave the corresponding α-ketoesters (5b-f) in moderate yields.The reactions of 1a with other organometallic reagents, e.g. phenylmagnesium (2a), -zinc (8) and -mercuric bromide (9) in the presence or in the absence of zinc chloride were examined.Furthermore, the addition of phosphonium ylide 13a to the cyano group of 1a in the presence of stannic chloride occured exclusively to give the phosphonium salt 14.The results are discussed in terms of the hard and soft acids and bases (HSAB) principle.Keywords - ethyl cyanoformate; benzoyl cyanide; organocadmium reagent; organozinc reagent; phosphonium ylide; cyano group addition; α-ketoester; α-dehydroamino ester; Lewis acid
- Akiyama, Yasunobu,Takebayashi, Shoko,Kawasaki, Tomomi,Sakamoto, Masanori
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p. 1800 - 1807
(2007/10/02)
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