- Catalytic acetoxylation of lactic acid to 2-acetoxypropionic acid, en route to acrylic acid
-
We present an alternative synthetic route to acrylic acid, starting from the platform chemical lactic acid and using heterogeneous catalysis. To improve selectivity, we designed an indirect dehydration reaction that proceeds via acetoxylation of lactic acid to 2-acetoxypropionic acid. This intermediate can then be pyrolized to acrylic acid. Acetic acid is used both as a reagent and a solvent in the first step, and may be recovered in the subsequent pyrolysis step. We tested a range of solid acid catalysts for the acetoxylation step (Y zeolites, sulfated zirconia, ion-exchange resins, sulfonated graphene, and various sulfonated silica gels and mixed oxides). Recycling studies were carried out for the most active catalysts. To enable quantitative analysis using gas chromatography we also developed a reliable silylation derivatization method, which is also reported. These results open opportunities for improving the biorenewable production of acrylic acid.
- Beerthuis, Rolf,Granollers, Marta,Brown, D. Robert,Salavagione, Horacio J.,Rothenberg, Gadi,Shiju, N. Raveendran
-
-
Read Online
- Ni-Catalyzed C(sp3)–O Arylation of α-Hydroxy Esters
-
A Negishi cross-coupling of α-hydroxy ester derivatives and arylzinc reagents has been developed. This reaction tolerates both primary and secondary C(sp3)–O alcohol precursors and achieves efficient cross-coupling under Ni catalysis without the need for added external metal reductant, photocatalyst, or additives. The arylation of readily accessible C(sp3)–O electrophiles in this operationally simple, rapid, and mild reaction provides a complementary way of accessing desirable α-aryl ester products.
- Monteith, John J.,Rousseaux, Sophie A. L.
-
supporting information
p. 9485 - 9489
(2021/12/09)
-
- Synthesis, pharmacological evaluation and molecular docking of novel R-/S-2-(2-hydroxypropanamido)-5-trifluoromethyl benzoic acid as dual anti-inflammatory anti-platelet aggregation agents
-
R-/S-2-(2-hydroxypropanamido) benzoic acid (R-/S-HPABA), marine-derived anti-inflammatory antiplatelet drugs, were initially synthesised in our group. However, preliminary research showed that R-/S-HPABA were eliminated rapidly because of extensive hydroxylation metabolism of phenyl ring in vivo. In order to reduce significant hydroxylation metabolism to improve pharmacological activity and bioavailability, trifluoromethyl group was incorporated into R-/S-HPABA to synthesise R-/S-2-(2-hydroxypropanamido)-5-trifluoromethyl benzoic acid (R-/S-HFBA), respectively. The purposes of this study were to report the synthesis of R-/S-HFBA and compare the anti-inflammatory antiplatelet effect and pharmacokinetic properties of R-/S-HFBA with those of R-/S-HPABA. Carrageenan-induced rat paw edema assay was used for the evaluation of the anti-inflammatory activity. R-/S-HFBA showed better results in inhibiting edema and were able to prolong the anti-inflammatory effect after carrageenan injection. The antiplatelet aggregation activity of R-/S-HFBA and R-/S-HPABA was studied on arachidonic acid-induced platelet aggregation of rabbit platelet-rich plasma. The aggregation inhibition rate of R-/S-HFBA was significantly (p max, larger AUC0-∞, and longer t1/2, which, as expected, are more metabolically stable.
- Rong, Rong,Zhang, Rui-zhen,Wang, Xin,Dan, Yu-han,Zhao, Yun-li,Yu, Zhi-guo
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p. 967 - 978
(2019/12/12)
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- Highly selective production of propionic acid from lactic acid catalyzed by NaI
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Propionic acid (PA), a valuable chemical widely used in the food and feed industry, is currently produced by the petrochemical industry. Selective production of PA from bio-based lactic acid (LA) is difficult due to the high activation energy of the hydroxyl group at the α position of the carboxyl group. Herein, a metal-free catalytic system for the highly selective transformation of bio-based LA to PA, which was used as the solvent to simplify the separation step, is reported using NaI as the catalyst. Under the optimal reaction conditions, a >99% yield of PA can be obtained from LA. A heat-induced radical-activated hydrogen mechanism was proposed based on the kinetic study and intermediate capture. The metal-free system can be reused five times without any loss in activity, and the PA product is easily separated. In addition, a two-step method using cellulose as the raw material to produce PA was conducted. This strategy offers a green and efficient approach to synthesize PA from biomass resources. This journal is
- Feng, Huan,Li, Teng,Liu, Shengqin,Rong, Nianxin,Wang, Yantao,Yang, Weiran
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p. 7468 - 7475
(2020/11/23)
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- NOVEL STING AGONISTS
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The present invention provides compounds of Formula I′: wherein , W, X, Y, Z, Z1, Z2, R1, R2, R3, R4 and R5 are as defined herein, or a stereoisomer, tautomer, pharmaceutically acceptable salt, prodrug ester or solvate form thereof, wherein all of the variables are as defined herein. These compounds are effective at modulating the STING protein and thus can be used as medicaments for treating or preventing disorders affected by the agonism of STING.
- -
-
Paragraph 0756; 0761; 0763
(2020/05/14)
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- AMINOPYRIDINE DERIVATIVES AS PHOSPHATIDYLINOSITOL PHOSPHATE KINASE INHIBITORS
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The invention relates to inhibitors of PI5P4K inhibitors useful in the treatment of cancers, neurodegenerative diseases, inflammatory disorders, and metabolic diseases, having the Formula: (I) where A, B, R1, X1, X2, and W are described herein.
- -
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Paragraph 0616
(2019/07/13)
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- CHROMENOPYRIDINE DERIVATIVES AS PHOSPHATIDYLINOSITOL PHOSPHATE KINASE INHIBITORS
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The invention relates to inhibitors of PI5P4K inhibitors useful in the treatment of cancers, neurodegenerative diseases, inflammatory disorders, and metabolic diseases, having the Formula (I); where A1, A2, G, R1, R2, R3, R4, and W are described herein.
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Paragraph 0364
(2019/07/13)
-
- Industrial preparation method of aclatonium napadisilate
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The invention discloses an industrial preparation method of aclatonium napadisilate. The industrial preparation method comprises the following steps that lactic acid reacts with acetic anhydride, chloroformate and N,N-dimethylethanolamine in sequence to obtain acetyllactylcholine, acetyllactylcholine is added with acid to be prepared into a salt and then separated, and a product reacts with 1,5-naphthalenedisulfonic acid dimethyl ester to obtain aclatonium napadisilate. The industrial preparation method has the advantages that aclatonium napadisilate is prepared by a ''mixed acid anhydride strategy'', and the use of a volatile highly corrosive reagent can be avoided; water can be used as a solvent for preparation of an intermediate, and the amount of an organic solvent can be avoided or reduced; a ''one-pot method'' can be adopted to prepare the intermediate to reduce unit operation; the solvent can be directly added for crystallization in the post-processing process of the preparationof a finished product to improve the purity of the product; and the reaction scale can be enlarged to more than ten kilograms.
- -
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Paragraph 0031-0044; 0047-0050
(2019/11/13)
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- PREPARATION METHOD OF ACRYLIC ACID FROM LACTIDE BY USING ION EXCHANGE RESIN
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The present invention relates to a method for manufacturing acrylic acid by dehydration of lactide derived from a biomass using a strongly acidic cation exchange resin. An object of the present invention is to provide the method for manufacturing acrylic acid, which is a high moisture absorbent raw material, in an environmentally friendly manner at a high yield and a high selectivity by using the strongly acidic cation exchange resin.COPYRIGHT KIPO 2019
- -
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Paragraph 0051-0054
(2019/10/10)
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- PREPARATION METHOD OF ACRYLIC ACID FROM LACTIDE BY USING ION EXCHANGE RESIN
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The present invention provides a method for manufacturing acrylic acid from a dehydration reaction of lactide derived from biomass using two or more strongly acidic cation exchange resins, for example, a strong acid cation exchange resin having a particle
- -
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Paragraph 0048-0054
(2019/10/11)
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- Design, synthesis, and evaluation of novel inhibitors for wild-type human serine racemase
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Most of the endogenous free D-serine (about 90%) in the brain is produced by serine racemase (SR). D-Serine in the brain is involved in neurodegenerative disorders and epileptic states as an endogenous co-agonist of the NMDA-type glutamate receptor. Thus, SR inhibitors are expected to be novel therapeutic candidates for the treatment of these disorders. In this study, we solved the crystal structure of wild-type SR, and tried to identify a new inhibitor of SR by in silico screening using the structural information. As a result, we identified two hit compounds by their in vitro evaluations using wild-type SR. Based on the structure of the more potent hit compound 1, we synthesized 15 derivatives and evaluated their inhibitory activities against wild-type SR. Among them, the compound 9C showed relatively high inhibitory potency for wild-type SR. Compound 9C was a more potent inhibitor than compound 24, which was synthesized by our group based upon the structural information of the mutant-type SR.
- Takahara, Satoyuki,Nakagawa, Kiyomi,Uchiyama, Tsugumi,Yoshida, Tomoyuki,Matsumoto, Kazunori,Kawasumi, Yasuo,Mizuguchi, Mineyuki,Obita, Takayuki,Watanabe, Yurie,Hayakawa, Daichi,Gouda, Hiroaki,Mori, Hisashi,Toyooka, Naoki
-
supporting information
p. 441 - 445
(2017/12/28)
-
- Total Synthesis of (+)-Prunustatin A: Utility of Organotrifluoroborate-Mediated Prenylation and Shiina MNBA Esterification and Macrolactonization to Avoid a Competing Thorpe-Ingold Effect Accelerated Transesterification
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A convergent total synthesis of (+)-prunustatin A is described through the assembly of two key fragments and a macrolactonization. Shiina MNBA couplings were used for the formation of each of the four ester bonds in the tetralactone ring, including the key macrocyclization which was essential to minimize competing Thorpe-Ingold accelerated transesterification. Other key steps included an organoboron-based prenylation using potassium prenyltrifluoroborate and a carbonyldiimidazole-mediated coupling to form the salicylamide.
- Chojnacka, Maja W.,Batey, Robert A.
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supporting information
p. 5671 - 5675
(2018/09/13)
-
- Modifying oligoalanine conformation by replacement of amide to ester linkage
-
Oligo(lactic acid) is an ester-analogue of short oligoalanine sequence and adopts a rigid left-handed helical structure. In this study, oligo(lactic acid) was incorporated into oligoalanine sequences and their conformations were studied by vibrational circular dichroism and electronic circular dichroism spectroscopy. The results suggested that oligo(lactic acid) moiety in these sequences maintains a left-handed helix and increases the conformational propensity of the oligoalanine moiety to form a left-handed polyproline type II-like helix. The importance of the chirality of oligo(lactic acid) moiety for the oligoalanine conformation was also studied. The results obtained in this study should be useful in developing ester-containing oligopeptides that function better than normal peptides.
- Hongen, Takahiro,Taniguchi, Tohru,Monde, Kenji
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supporting information
p. 396 - 401
(2018/02/13)
-
- Synthesis of sialic acid derivatives based on chiral substrate-controlled stereoselective aldol reactions using pyruvic acid oxabicyclo[2.2.2]octyl orthoester
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The synthesis of sialic acids and their analogs was accomplished based on substrate-controlled asymmetric aldol reactions between sterically complicated aldehydes easily prepared from commercially available carbohydrates and a novel pyruvic acid oxabicyclo[2.2.2]octyl orthoester. Systematic aldol reaction studies using chiral aldehydes revealed that α,β,γ-benzyloxy-substituted aldehydes with an α,β-anti relative configuration preferentially provided the Felkin products with the 4,5-anti configuration with high diastereoselectivity. The relative β,γ-configuration in α,β,γ-benzyloxy-substituted aldehydes with an α,β-syn arrangement exerted a secondary effect on the diastereoselectivity of the stereogenic center formed in aldol reactions, and α,β-syn-β,γ-anti benzyloxyaldehyde exhibited superior diastereoselectivity to α,β-syn-β,γ-syn benzyloxyaldehyde to yield the Felkin products.
- Norimura, Yusuke,Yamamoto, Daisuke,Makino, Kazuishi
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supporting information
p. 640 - 648
(2017/01/25)
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- Preparation method and application of 2-lactoyl aminobenzoic acid
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The invention relates to a new medicinal application of a chiral compound. The chiral compound is chemically named as R-/S-2-lactoyl aminobenzoic acid and has a structural formula as follows: formula (shown in the description). The compound is initially extracted and separated from secondary metabolite of microorganisms and can be obtained by virtue of a chemical synthetic method. An initial pharmacology experiment shows that the compound has good pain-easing and anti-inflammation activities and relatively low stimulation to gastrointestinal tracts. Recent researches prove that the compound has relatively good anti-platelet aggregation and anti-thrombus activities and is expected to be a novel non-steroidal anti-platelet aggregation and anti-thrombus drug.
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-
Paragraph 0037; 0038
(2017/08/30)
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- Compounds And Compositions for the Treatment of Ocular Disorders
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The disclosure describes prodrugs and derivatives of prostaglandins, carbonic anhydrase inhibitors, kinase inhibitors, beta-adrenergic receptor antagonists and other drugs, as well as controlled delivery formulations containing such prodrugs and derivatives, for the treatment of ocular disorders.
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Paragraph 0503
(2017/04/11)
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- METHODS AND COMPOSITIONS FOR PREVENTING OPIOID ABUSE
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Abuse-resistant opioid compounds, drug delivery systems, pharmaceutical compositions comprising an opioid covalently bound to a chemical moiety are provided. Methods of delivering an active ingredient to a subject and methods of preventing opioid abuse are also provided.
- -
-
Paragraph 0705; 0706
(2016/11/28)
-
- Total synthesis of actinophenanthroline A via double Doebner–Miller reaction
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Total synthesis of actinophenanthroline A, a marine actinomycete within the family of Streptomycetaceae (strain CNQ-149) is reported. Both the racemic and enantiopure actinophenanthroline A have been synthesized with good overall yields. Highlight of the synthesis contains the classical and economical double Doebner–Miller reaction to access the 1,7-phenanthroline core followed by a modified EDCI coupling.
- Ghosh, Suman Kr,Nagarajan, Rajagopal
-
supporting information
p. 4009 - 4011
(2016/08/17)
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- CARBONYLATION OF ETHYLENICALLY UNSATURATED COMPOUNDS
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PROBLEM TO BE SOLVED: To provide a process for the carbonylation of ethylenically unsaturated compounds including vinyl esters and a process for the production of 3-hydroxypropanoate esters or 3-hydroxypropanoic acids. SOLUTION: The process comprises reacting the compound with carbon monoxide in the presence of a source of hydroxyl groups and of a catalyst system. The catalyst system is obtainable by combining: (a) a metal of Group 8, 9 or 10 or a compound thereof: and (b) a bidentate ligand of general formula (I): X1(X2)-Q2-A-R-B-Q1-X3(X4). COPYRIGHT: (C)2015,JPOandINPIT
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Paragraph 0234-0236
(2016/10/09)
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- 3-Aminoquinazolinones as chiral ligands in catalytic enantioselective diethylzinc and phenylacetylene addition to aldehydes
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A series of readily known enantiomerically pure 3-aminoquinazolinones 1a-d were synthesised from easily accessible chiral pool α-hydroxy acids and α-amino acids in only four steps without any requirement of chromatography. These quinazolinones were examined as chiral ligands for catalytic enantioselective diethylzinc and phenylacetylene additions to aldehydes. For enantioselective alkylations, the effects of temperature, solvent, diethylzinc and ligand criteria were analysed, and the desired chiral alcohols were obtained in up to 86% ee. 3-Aminoquinazolinones 1a-d were also shown to be very useful ligands in enantioselective alkynylations of aldehydes. Based upon the optimised conditions, the corresponding propargylic alcohols were obtained in up to 94% ee.
- Karabuga, Semistan,Karakaya, Idris,Ulukanli, Sabri
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p. 851 - 855
(2014/06/23)
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- CONTINUOUS PROCESS FOR THE PREPARATION OF (S)-2-ACETYLOXYPROPIONIC ACID CHLORIDE
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The present invention relates to a continuous method for the preparation of (S)-2-acetyloxypropionic acid from an aqueous solution of lactic acid and acetic anhydride, in acetic acid. (S)-2-acetyloxypropionic acid is used for the preparation of (S)-2-acetyloxypropionic acid chloride, an essential intermediate compound for the preparation of Iopamidol and has to be industrially produced with high purity and suitable quality for producing Iopamidol according to the Pharmacopoeia requirements. The continuous process according to the invention, comprises therefore also the chlorination steps of (S)-2-acetyloxypropionic acid with thionyl chloride to give the corresponding (S)-2-acetyloxypropionic acid chloride which is further distilled to give the suitable purity characteristics for its use for the preparation of non-ionic iodinated contrast agents as Iopamidol.
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Page/Page column 16-17
(2014/07/07)
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- An efficient synthesis of dichotomine a via cyclization of l-tryptophan derivative
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A new synthetic method for dichotomine A is reported. The key step of the synthetic process is the efficient cyclization of L-tryptophan derivative via a modified Bischler-Napieralski reaction which aluminium chloride is used as a mild catalyst. Dichotomine A is obtained in 5 steps and 63.9 % yield.
- Shi, Xiu Xiao,He, Dian,Li, Shao Bai,Lei, Xin,Yang, Huan
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p. 6387 - 6390
(2013/07/26)
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- Reactions of hydrogen peroxide with acetylacetone and 2- acetylcyclopentanone
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A reaction of acetylacetone with equimolar amount of concentrated aqueous H2O2 in both organic solvents (ButOH, AcOH) and water at various temperatures gave the corresponding 3,5-dihydroxy-1,2- dioxolanes with different configuration of stereogenic centers. In the pres-ence of an excess of H2O2, 3,5-dihydroxy-1,2-dioxolanes were converted to a mixture of 5-hydroperoxy-3-hydroxy-1,2-dioxolanes and further to a mixture of dimeric 1,2-dioxolan-3-ylperoxides. All the peroxides formed exist in solutions as equilibrium mixtures with the starting reagents. A prolonged reflux of solutions of 3,5-dihydroxy-1,2-dioxolanes in ButOH in the presence of a large excess of H2O2 led to the skeletal rearrangements of the substrates to a mixture of propionic acid and hydroxyacetone, which underwent further oxidative transfor-mations. Unlike acetylacetone, 2-acetylcyclopentanone reacted with H2O2 in aqueous phase or in solutions in ButOH under thermodynamic or kinetic control with the formation of the corresponding 5-hydroperoxy-3-hydroxy- 1,2-dioxolanes, rather than 3,5-dihydroxy-1,2-di-oxolanes. Thermodynamically controlled process in solution in AcOH gave a mixture of all four possible hydroperoxyhydroxy-1,2-dioxolanes. These cyclic peroxides in solutions in ButOH or AcOH readily converted to a mixture of AcOH, glutaric, α-methyladipic, and α-hydroxy-α-methyladipic acids. An active α-hydroxylation of the substrate was observed upon reflux of a solution of 2-acetylcyclopentanone and H2O2 in AcOH.
- Novikov,Shestak
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p. 2171 - 2190
(2014/11/07)
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- PARASITICIDAL COMPOUNDS, METHODS, AND FORMULATIONS
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Provided are dihydroisoxazole compounds useful for controlling parasites both in animals and agriculture. Further provided are methods for controlling parasite infestations of an animal by administering an effective amount of a compound as described above, or a pharmaceutically acceptable salt thereof, to an animal, as well as formulations for controlling parasite infestations using the compounds described above or an acceptable salt thereof, and an acceptable carrier. Also provided are compounds and processes useful for making the dihydroisoxazole compounds.
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Page/Page column 70
(2012/12/13)
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- PARASITICIDAL DIHYDROISOXAZOLE COMPOUNDS
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Provided are dihydroisoxazole compounds I useful for controlling parasites both in animals and agriculture. Further provided are methods for controlling parasite infestations of an animal by administering an effective amount of a compound as described above, or a pharmaceutically acceptable salt thereof, to an animal, as well as formulations for controlling parasite infestations using the compounds described above or an acceptable salt thereof, and an acceptable carrier. Also provided are compounds and processes useful for making the dihydroisoxazole compounds.
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Page/Page column 70
(2012/12/13)
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- Acrylic Acid from Lactide and Process
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Technical grade acrylic acid derived from renewable resources utilizing a homogeneous nickel catalyst system by a process including reacting lactide with acetic acid to form 2-acetoxypropionic acid in the presence of a homogeneous nickel catalyst, pyrolyzing, with or without a catalyst, the 2-acetoxypropionic acid to acrylic acid and acetic acid, condensing and collecting the pyrolysis products in the presence of polymerization inhibitor(s) and purfying the acrylic acid by distillation in the presence of polymerization inhibitor(s). Acrylic acid and methyl acrylate are produced from methyl 2-acetoxypropionate which comes from fermentation derived lactic acid. The disclosed process will produce a “green” (i.e. renewable resources derived) acrylic acid and methyl acrylate ester.
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Page/Page column 3
(2012/04/05)
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- Mimics of the self-assembling chlorosomal bacteriochlorophylls: Regio- and stereoselective synthesis and stereoanalysis of acyl(1-hydroxyalkyl)porphyrins
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Diacylation of copper 10,20-bis(3,5-di-tert-butylphenylporphyrin) using Friedel-Crafts conditions at short reaction times, high concentrations of catalyst, and 0-4°C affords only the 3,17-diacyl-substituted porphyrins, out of the 12 possible regioisomers. At longer reaction times and higher temperatures, the 3,13-diacyl compounds are also formed, and the two isomers can be conveniently separated by normal chromatographic techniques. Monoreduction of these diketones affords in good yields the corresponding acyl(1-hydroxyalkyl) porphyrins, which after zinc metalation are mimics of the natural chlorosomal bacteriochlorophyll (BChl) d. Racemate resolution by HPLC on a variety of chiral columns was achieved and further optimized, thus permitting easy access to enantiopure porphyrins. Enantioselective reductions proved to be less effective in this respect, giving moderate yields and only 79% ee in the best case. The absolute configuration of the 31-stereocenter was assigned by independent chemical and spectroscopic methods. Self-assembly of a variety of these zinc BChl d mimics proves that a collinear arrangement of the hydroxyalkyl substituent with the zinc atom and the carbonyl substituent is not a stringent requirement, since both the 3,13 and the 3,17 regioisomers self-assemble readily as the racemates. Interestingly, the separated enantiomers self-assemble less readily, as judged by absorption, fluorescence, and transmission electron microscopy studies. Circular dichroism spectra of the self-assemblies show intense Cotton effects, which are mirror-images for the two 3 1-enantiomers, proving that the supramolecular chirality is dependent on the configuration at the 31-stereocenter. Upon disruption of these self-assemblies with methanol, which competes with zinc ligation, only very weak monomeric Cotton effects are present. The favored heterochiral self-assembly process may also be encountered for the natural BChls. This touches upon the long-standing problem of why both 31-epimers are encountered in BChls in ratios that vary with the illumination and culturing conditions.
- Balaban, Teodor Silviu,Bhise, Anil Dnyanoba,Bringmann, Gerhard,Buerck, Jochen,Chappaz-Gillot, Cyril,Eichhoefer, Andreas,Fenske, Dieter,Goetz, Daniel C. G.,Knauer, Michael,Mizoguchi, Tadashi,Moessinger, Dennis,Roesner, Harald,Roussel, Christian,Schraut, Michaela,Tamiaki, Hitoshi,Vanthuyne, Nicolas
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supporting information; scheme or table
p. 14480 - 14492
(2010/03/02)
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- tert-butyl (2S)-(p-tolylsulfonyloxy)propionate - A suitable reagent for the direct alkylation of indole derivatives
-
A new method is proposed for the synthesis of indole derivatives containing a chiral substituent at the nitrogen atom, which includes the direct alkylation of indole derivatives with tert-butyl (2S)-(p-tolylsulfonyloxy)propionate, obtained from commercial ethyl (S)-lactate with subsequent conversion to the corresponding p-toluenesulfonyloxy derivative by hydrolysis, and esterification.
- Kurkin,Belov,Yurovskaya
-
scheme or table
p. 1123 - 1128
(2009/05/26)
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- Zinc-catalyzed enantiospecific sp3-sp3 cross-coupling of α-hydroxy ester triflates with grignard reagents
-
(Chemical Equation Presented) Zinc chloride does the trick and efficiently catalyzes the enantiospecific cross-coupling of α-hydroxy ester triflates with Grignard reagents under mild conditions. Enantiopure α-hydroxy esters are directly available from the chiral pool or by diazotization of α-amino acids. Substantial variations in both reacting partners are tolerated making this methodology an attractive alternative to enolate alkylation featuring a reversal of polarity.
- Studte, Christopher,Breit, Bernhard
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supporting information; experimental part
p. 5451 - 5455
(2009/03/12)
-
- PROCESS FOR THE PREPARATION OF HYDROXY CARBOXYLIC ACID
-
The present invention provides a three step process for the preparation of hydroxy carboxylic acid. The present invention involves the hydroformylation of enol ester (e.g. vinyl acetate) using a cobalt catalyst (e.g. Co2(CO)8), optionally a promoter or a ligand containing O, N, N—O, P, As or Sb atom/s, to obtain a mixture of 2-acetoxy carboxaldehyde (e.g. 2-acetoxy propanal) and 3-acetoxy carboxaldehyde (e.g. 3-acetoxy propanal), oxidizing the product acetoxy carboxyaldehydes to the corresponding acetoxy carboxylic acid, in presence or absence of a Gr. 8 metal catalyst, followed by hydrolyzation of the product acetoxy carboxylic acids to the corresponding desired hydroxy carboxylic acids, in presence of an acidic catalyst and separating the catalyst and reusing it for another hydrolysis step.
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Page/Page column 3
(2008/06/13)
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- Reaction of thallium(III) salts with homoallylic alcohols: Ring contraction vs. dimethoxylation
-
The oxidation of 2-(3,4-dihydronaphthalen-1-yl)-ethanol (1) with a variety of thallium(III) salts was investigated. An indan, formed by a ring contraction reaction, was obtained in good to moderate yields under a variety of reaction conditions: i) thallium triacetate (TTA) in aqueous AcOH; ii) thallium tris-trifluoroacetate (TTFA) in aqueous TFA; iii) TTFA in CH2Cl 2; iv) thallium tripropionate (TTP) in aqueous propionic acid and v) thallium tris-[(S)-(-)-triacetoxypropionate] in aqueous (S)-(-)-2- acetoxypropionic acid. On the other hand, the reaction of compound 1 with TTA in methanol led to a 2:1 mixture of the corresponding cis- and trans-dimethoxylated compounds, respectively. These compounds were formed by a thallium-promoted addition of methanol to the double bond.
- Silva Jr., Luiz F.,Craveiro, Marcus V.
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p. 1419 - 1428
(2007/10/03)
-
- Quinazolinone-based fungal efflux pump inhibitors. Part 1: Discovery of an (N-methylpiperazine)-containing derivative with activity in clinically relevant Candida spp.
-
The discovery of a series of quinazolinone-based fungal efflux pump inhibitors by high-throughput screening for potentiation of fluconazole in C. albicans is described. Attempts to improve the aqueous solubility of screening hits led to the discovery of an analog with greatly improved physical properties and activity against clinically-relevant Candida spp.
- Lemoine, Rémy C.,Glinka, Tomasz W.,Watkins, William J.,Cho, Aesop,Yang, Jessie,Iqbal, Nadeem,Singh, Rajeshwar,Madsen, Deidre,Lolans, Karen,Lomovskaya, Olga,Oza, Uma,Dudley, Michael N.
-
p. 5127 - 5131
(2007/10/03)
-
- Fungal efflux pump inhibitors
-
This invention relates to compounds that are efflux pump inhibitors and therefore are useful as potentiators of anti-fungal agents for the treatment of infections caused by fungi that employ an efflux pump resistance mechanism.
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-
-
- Synthesis and characterization of chiral N-O turns induced by α-aminoxy acids
-
Chiral α-aminoxy acids of various side chains were synthesized with high optical purity starting from chiral α-amino acids. The conformations of diamides 13a-e, 15, and 16 were probed by using NMR, FT-IR, and CD spectroscopic methods as well as X-ray crystallography. The right-handed turns with eight-membered-ring intramolecular hydrogen bonds between adjacent residues (called the N-O turns) were found to be preferred for D-aminoxy acid residues, and they were independent of the side chains. The rigid chiral N-O turns should have great potential in molecular design.
- Yang,Li,Ng,Yan,Qu,Wu
-
p. 7303 - 7312
(2007/10/03)
-
- SHORT CHAIN 2-HYDROXYCARBOXYLIC ACID-BASED DERIVATIVES OF CERAMIDES
-
The present invention relates to active ceramide derivatives. Specifically, the invention relates to 2(alpha)-hydroxycarboxylic acid-based ceramide derivatives. The present invention describes a method for obtaining these compounds. The invention also relates to the use of these compounds in cosmetic compositions.
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-
-
- Atropisomeric amides: Stereoselective enolate chemistry and enantioselective synthesis via a new SmI2-mediated reduction
-
The use of certain types of atropisomeric amides, incorporating an N-MEM-ortho-tert-bityariume group, for stereoselective reactions, has been explored. Enolate reactions of these systems are highly diastereocontrolled, and enantiomerically enriched starting materials can be obtained, starting from lactic acid, via a new SmI2 mediated reduction process.
- Hughes, Adam D.,Price, David A.,Simpkins, Nigel S.
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p. 1295 - 1304
(2007/10/03)
-
- A simple procedure for the synthesis of enantiopure α-acetoxy ketones
-
Cross-coupling reactions of α-acetoxy carboxylic acid chlorides with organocopper reagents, derived from Grignard reagents, cuprous bromide and lithium bromide, provide a simple and straightforward method for the synthesis of enantiopure α-acetoxy ketones.
- Babudri, Francesco,Fiandanese, Vito,Marchese, Giuseppe,Punzi, Angela
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p. 2431 - 2440
(2007/10/03)
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- Preparation and use of (S)-O-acetyllactyl chloride (Mosandl's reagent) as a chiral derivatizing agent
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(S)-O-Acetyllactyl chloride is used as a versatile chiral derivatizing agent for the chromatographic determination of the enantiomeric excesses of alcohols or amines. However, some precautions must be taken to avoid its racemization during preparation and use. In addition, the racemic counterpart of this reagent can be used to determine the best analytical separation conditions.
- Buisson, Didier,Azerad, Robert
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p. 2997 - 3002
(2007/10/03)
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- SmI2-mediated reduction of α-functionalised amides: Highly enantiospecific access to an atropisomeric amide
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SmI2 or SmI2-LiCl mixtures can be used to reduce α-functionalised amides in yields of up to 85% depending upon the amide structure. The method has been applied to the synthesis of an atropisomeric anilide system in highly enantioenriched form, starting with (S)-O-acetyl lactic acid.
- Hughes, Adam D.,Simpkins, Nigel S.
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p. 967 - 968
(2007/10/03)
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- First Asymmetric Synthesis of (S)-(-)-2-(1-Hydroxyethyl)-quinazolin-4(3H)-one (Chrysogenine), a Fungal Metabolite, and Confirmation of the Proposed Absolute Configuration
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Chiral (S)-(-)-2-(1-hydroxyethyl)quinazolin-4(3H)-one (chrysogenine; 7), a fungal metabolite, has been synthesised from anthranilamide and S-(+)-lactic acid, confirming the proposed absolute configuration.
- Maiti, Dilip K.,Ghoshdastidar, Partha Pratim,Bhattacharya, Pranab K.
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p. 306 - 307
(2007/10/03)
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- Enantioselective Preparation of α-Acyloxy Ketones from α-Hydroxy and α-Amino Acids
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Various chiral α-acyloxy ketones have been easily prepared, in high yields with an excellent enantiomeric purity, by acylation of organomanganese reagents with the corresponding α-acyloxy carboxylic acid chlorides prepared from α-hydroxy and α-amino acids.
- Cahiez, Gerard,Metais, Eric
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p. 6449 - 6452
(2007/10/02)
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- Resolution of Racemic Carboxylic and Sulfonic Acids via D-Xylose Derived New Cyclic Carbamate Reagents (Oxazolidin-2-ones)
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Two new chiral oxazolidin-2-ones have been easily prepared from D-xylose and studied as chiral derivatizing agents (CDA's) for the resolution of racemic carboxylic and sulfonic acids.The resultant diastereomers are readily separated by chromatographic methods and easily hydrolyzed to isolate the resolved materials in high optical purities and to return the CDA's for reuse.
- Koell, Peter,Luetzen, Arne
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- The Rational Design and Application of New Chiral Phosphonates for the Enantiomeric Excess Determination of Unprotected Amino Acids. Remarkable pH Dependency of the Diastereomeric Shift Differences.
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Diastereomeric amide derivatives of chiral phosphorinane 8 and unprotected amino acids are easily prepared in aqueous solutions, showing well separated signals in the 31P NMR spectra allowing accurate enentiomeric excess determination.Moreover, the obtained diastereomeric shift dispersion appears to be highly pH dependent, indicating the influence of intramolecular ion pair formation on the diastereomeric shift dispersion.
- Hulst, Ron,Vries, N. Koen de,Feringa, Ben L.
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p. 11721 - 11728
(2007/10/02)
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- Hydrogen-bond-mediated folding in depsipeptide models of β-turns and α-helical turns
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The folding of several depsipeptides constructed from α-amino acids [L-proline (P) and L-alanine (A)] and α-hydroxy acids [L-lactic acid (L) and glycolic acid (G)] has been examined in methylene chloride solution by variable- temperature IR spectroscopy. Additional studies have been conducted in some cases, involving variable-temperature 1H NMR spectroscopy and molecular mechanics calculations. The depsipeptides include three-residue molecules (PLL, ALL, and PLG) that can form a 13-membered-ring amide-to-amide hydrogen bond, which, for a peptide backbone, would correspond to a single turn of an α-helix. These depsipeptides can also form 10-membered-ring amide-to-ester hydrogen bonds, which would correspond to β-trun formation for a peptide backbone. For PLL and PLG, distinct N-H stretch bands can be identified for three folding patterns: non-hydrogen-bonded, β-turn, and α-helical turn. IR-based van't Hoff analyses for PLL indicate that the α-helical turn and the β-turn are both modestly enthalpically favored relative to the non-hydrogen-bonded state, but neither turn is enthalpically preferred over the other. For PLG, in contrast, the α-helical turn appears to be enthalpically preferred over both of the alternative folding patterns. Comparison between PLL and ALL indicates that the N-terminal proline residue favors α-helical turn formation. The strengths of amide-to-amide and amide-to-ester hydrogen bonds have been compared in the context of a β-turn geometry by analyzing LG and AG in CH2Cl2. The amide-to-amide hydrogen bond is enthalpically favored by ca. 1.6 kcal/mol, but formation of this enthalpically stronger intramolecular hydrogen bond is more costly entropically. Extrapolation from the behavior of these depsipeptides leads us to predict that for tripeptides in a nonpolar environment, a β-turn will generally be enthalpically preferred over an isolated α-helical turn. β-Turn folding has previously been widely studied in model peptides and depsipeptides; however, the present report appears to represent the first experimental effort to model formation of a single α-helical turn.
- Gallo, Elizabeth A.,Gellman, Samuel H.
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p. 9774 - 9788
(2007/10/02)
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- Synthesis of Chiral Zileuton, A Potent And Selective Inhibitor Of 5-Lipoxygenase
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Coupling and intramolecular Wittig reaction of N-benzyloxy-D-alanine anhydride (13) and (2-Mercaptophenyl)methyltriphenylphosphonium bromide (3) were used as key steps to prepare (+)-enantiomer of zileuton (1), a potent and selective inhibitor of 5-lipoxygenase.
- Hsiao, Chi-Nung,Kolasa, Teodozyj
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p. 2629 - 2632
(2007/10/02)
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- Amination with 3-acetoxyaminoquinazolin-4-(3H)ones: Preparation of α-aminoacid esters by reaction with silyl ketene acetals followed by N-N bond cleavage
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Solutions of 3-acetoxyaminoquinazoline (5) react with enol ethers and silyl ketene acetals to give α-aminoaldehyde α-aminoketone or α-aminoacid derivatives. Acylation of the exocyclic nitrogen in these derivatives, as a preliminary to reductive N-N bond cleavage, could only be accomplished by indirect means. Samarium diiodide, however, effected the reduction of this N-N bond without the necessity for N-acylation. Solutions of the corresponding enantiopure 3-acetoxyaminoquinazolinone (34) brought about the disastereoselective amination of the prochiral silyl ketene acetal (15) and reductive N-N bond cleavage of the major disastereoisomer lead to enantiopure 2-phenylalanine methyl ester.
- Atkinson,Kelly,Williams
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p. 7713 - 7730
(2007/10/02)
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- Molecular Sieve Controlled Diastereoselectivity: Effect in the Palladium-Catalyzed Cyclization of cis-1,2-Divinylcyclohexane with α-Oxygen-Substituted Acids as Chiral Nucleophiles
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Molecular sieves have been shown to improve greatly the stereoselectivity in the palladium(II)-catalyzed reaction of cis-1,2-divinylcyclohexane with chiral acids.Reactions run with molecular sieves and derivatives of (R)-lactic acids as nucleophiles always yielded products with S configuration at the newly formed chiral center in contrast to reactions without molecular sieves that gave products with either S or R configuration at this chiral center.It appears that this effect has not been observed previously.Only water-containing molecular sieves increased the stereoselectivity.A chiral palladium complex was formed faster in the presence of molecular sieves, but use of this complex as catalyst in the cyclization did not result in increased selectivity.The best stereoselectivity was found for molecular sieves with a high sodium content (Lancaster 13X and 4-Angstroem sieves).
- Tottie, Louise,Baeckstroem, Peter,Moberg, Christina,Tegenfeldt, Joergen,Heumann, Andreas
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p. 6579 - 6587
(2007/10/02)
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- A Rule To Predict Which Enantiomer of a Secondary Alcohol Reacts Faster in Reactions Catalyzed by Cholesterol Esterase, Lipase from Pseudomonas cepacia, and Lipase from Candida rugosa
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The enantioselectivity of the title enzymes for more than 130 esters of secondary alcohols is correlated by a rule based on the sizes of the substituents at the stereocenter.This rule predicts which enantiomer of a racemic secondary alcohol reacts faster for 14 of 15 substrates of cholesterol esterase (CE), 63 of 64 substrates of lipase from Pseudomonas cepacia (PCL), and 51 of 55 cyclic substrates of lipase from Candida rugosa (CRL).The enantioselectivity of CRL for acyclic secondary alcohols is not reliably predicted by this rule.This rule implies that the most efficiently resolved substrates are those having substituents which differ significantly in size.This hypothesis was used to design syntheses of two chiral synthons: esters of (R)-lactic acid and (S)-(-)-4-acetoxy-2-cyclohexen-1-one, 70.As predicted, the acetate group of the methyl ester of lactyl acetate was hydrolyzed by PCL with low enantioselectivity because the two substituents, CH3 and C(O)OCH3, are similar in size.To improve enantioselectivity, the methyl ester was replaced by a t-butyl ester.The acetate group of the tert-butyl ester of lactyl acetate was hydrolyzed with high enantioselecticity (E > 50).Enantiomerically pure (R)-(+)-tert-butyl lactate (>98percent ee, 6.4 g) was prepared by kinetic resolution.For the second example, low enantioselectivity (E 65) using either CE or CRL.Enantiomerically pure 70 (98percent ee) was obtained after removal of the bromines with zinc and oxidation with CrO3/pyridine.
- Kazlauskas, Romas J.,Weissfloch, Alexandra N. E.,Rappaport, Aviva T.,Cuccia, Louis A.
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p. 2656 - 2665
(2007/10/02)
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- Process for the preparation of intermediates for the synthesis of fosfomycin
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A process is described for the preparation of intermediates useful in the synthesis of Fosfomycin. More particularly, an enantioselective process is described for the preparation of derivatives of (1S,2S)-1,2-dihydroxypropyl-phosphonic acid of formula STR1 wherein R2 and R3 have the meanings reported in the specification.
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- Process for the preparation of intermediates for the synthesis of fosfomycin
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A process is described for the preparation of intermediates useful in the synthesis of Fosfomycin. More particularly, an enantioselective process is described for the preparation of derivatives of (1S,2S)-1,2-dihydroxypropyl--phosphonic acid of formula wherein R2 and R3 have the meanings reported in the specification.
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