cas 24008-63-7, (S)-MANDELAMIDE | Articles data

Articles about 24008-63-7Total 60 be found

Article title
Article abstract
Author
Journal number and time
Download

Hydration of Cyanohydrins by Highly Active Cationic Pt Catalysts: Mechanism and Scope
Cyanohydrins (α-hydroxy nitriles) are a special type of nitriles that readily decompose into hydrogen cyanide (HCN) and the corresponding carbonyl compounds. Hydration of cyanohydrins that are readily available through cyanation of aldehydes and ketones provides the most straightforward route to valuable α-hydroxyamides. However, due to low stability of cyanohydrins and deactivation of the catalysts by the released HCN, catalytic direct hydration of cyanohydrins still remains largely unsolved. As a general trend, cyanohydrins containing bulkier substituents, such as α,α-diaryl cyanohydrins, degrade more quickly and thus are more difficult to be hydrated. Here, we report development of cationic platinum catalysts that exhibit high reactivity for hydration of various cyanohydrins. Detailed mechanistic investigations for hydration of nitriles by (PμP)Pt(PR2OH)X(OTf) reveal a catalytic cycle involving the formation of a five-membered metallacyclic intermediate and subsequent hydrolysis via attacking on the phosphorus of the secondary phosphine oxide (PR2OH) ligand by H2O. We discovered that Pt catalyst A bearing the electron-rich, appropriately small-bite-angle bisphosphine ligand provides super reactivity for hydration of cyanohydrins. The hydration reactions catalyzed by A proceed at ambient temperatures and occur with a wide variety of cyanohydrins, including the most difficult α,α-diaryl cyanohydrins, with good turnover numbers.
Li, Chengcheng,Chang, Xiao-Yong,Huo, Luqiong,Tan, Haibo,Xing, Xiangyou,Xu, Chen
p. 8716 - 8726
(2021/07/26)

One-pot method for the synthesis of 1-aryl-2-aminoalkanol derivatives from the corresponding amides or nitriles
We have identified a novel one-pot method for the synthesis of β-amino alcohols, which is based on C-H bond hydroxylation at the benzylic α-carbon atom with a subsequent nitrile or amide functional group reduction. This cascade process uses molecular oxygen as an oxidant and sodium bis(2-methoxyethoxy)aluminum hydride as a reductant. The substrate scope was examined on 30 entries and, although the respective products were provided in moderate yields only, the above simple protocol may serve as a direct and powerful entry to the sterically congested 1,2-amino alcohols that are difficult to prepare by other routes. The plausible mechanistic rationale for the observed results is given and the reaction was applied to a synthesis of a potentially bioactive target. This journal is
Bobal, Pavel,Otevrel, Jan,Svestka, David
p. 25029 - 25045
(2020/07/14)

Catalyst, preparation method thereof and preparation method of amide compound
The invention relates to a catalyst, a preparation method thereof, and a preparation method for hydrating nitrile groups into amides. The catalyst is used for catalyzing nitrile groups to be hydratedinto amides, and the structural general formula of the catalyst is shown in the specification. In the formula, a plurality of R are respectively and independently ones selected from aromatic groups, heteroaromatic groups and non-aromatic ring groups; a plurality of R are ones respectively and independently selected from linear alkyl groups and alkane aromatic groups; X is one selected from Cl and Br; and L is one selected from OTf, BF4, PF6 and SbF6. The catalyst can catalyze nitrile groups to be hydrated into amides, and the nitrile groups can be catalyzed to be hydrated into amides even at a low temperature (20-80 DEG C); besides, compared with existing common catalysts for catalyzing nitrile groups to be hydrated into amides, the catalyst has the advantages that the equivalent weight of the catalyst can be obviously reduced, and nitrile groups can reach a relatively high conversion rate when the equivalent weight of the catalyst is only 0.01 mol%-0.5 mol%; and meanwhile, the catalyst is wider in application range and can catalyze various nitrile compounds to be hydrated into amide compounds.
-
Paragraph 0142-0146; 0147

(2020/01/12)

Catalytic Transfer Hydration of Cyanohydrins to α-Hydroxyamides
We report the palladium(II)-catalyzed transfer hydration of cyanohydrins to α-hydroxyamides by using carboxamides as water donors. This method enables selective hydration of various aldehyde- and ketone-derived cyanohydrins to afford α-mono- and α,α-disubstituted-α-hydroxyamides, respectively, under mild conditions (50 °C, 10 min). The direct conversion of fenofibrate, a drug bearing a benzophenone moiety, into a functionalized α,α-diaryl-α-hydroxyamide was achieved by means of a hydrocyanation-transfer hydration sequence. Preliminary kinetic studies and the synthesis of a site-specifically 18O-labeled α-hydroxyamide demonstrated the carbonyl oxygen transfer from the carboxamide reagent into the α-hydroxyamide product.
Kanda, Tomoya,Naraoka, Asuka,Naka, Hiroshi
supporting information
p. 825 - 830
(2019/01/14)

Bifunctional organometallic catalysts for selective hydration of nitriles to amides
In this report, we highlight our recent contributions towards the development of bifunctional catalysts for selective hydration of nitriles to amides.
Singh, Kuldeep,Sarbajna, Abir,Bera, Jitendra K.
p. 853 - 861
(2020/06/26)

Highly Active Platinum Catalysts for Nitrile and Cyanohydrin Hydration: Catalyst Design and Ligand Screening via High-Throughput Techniques
Nitrile hydration provides access to amides that are indispensable to researchers in chemical and pharmaceutical industries. Prohibiting the use of this venerable reaction, however, are (1) the dearth of biphasic catalysts that can effectively hydrate nitriles at ambient temperatures with high turnover numbers and (2) the unsolved challenge of hydrating cyanohydrins. Herein, we report the design of new "donor-acceptor"-type platinum catalysts by precisely arranging electron-rich and electron-deficient ligands trans to one other, thereby enhancing both the nucleophilicity of the hydroxyl group and the electrophilicity of the nitrile group. Leveraging a high-throughput, automated workflow and evaluating a library of bidentate ligands, we have discovered that commercially available, inexpensive DPPF [1,1′-ferrocenendiyl-bis(diphenylphosphine)] provides superior reactivity. The corresponding "donor-acceptor"-type catalyst 2a is readily prepared from (DPPF)PtCl2, PMe2OH, and AgOTf. The enhanced activity of 2a permits the hydration of a wide range of nitriles and cyanohydrins to proceed at 40 °C with excellent turnover numbers. Rational reevaluation of the ligand structure has led to the discovery of modified catalyst 2c, harboring the more electron-rich 1,1′-bis[bis(5-methyl-2-furanyl)phosphino] ferrocene ligand, which demonstrates the highest activity toward hydration of nitriles and cyanohydrins at room temperature. Finally, the correlation between the electron-donating ability of the phosphine ligands with catalyst efficiencies of 2a, 2c, 2d, and 2e in the hydration of nitrile 7 are examined, and the results support the "donor-acceptor" hypothesis.
Xing, Xiangyou,Xu, Chen,Chen, Bo,Li, Chengcheng,Virgil, Scott C.,Grubbs, Robert H.
supporting information
p. 17782 - 17789
(2019/01/04)

Mild and efficient enantioselective synthesis of all stereoisomers of cordiarimide B and their antioxidant study
Four isomers of cordiarimide B were synthesized by coupling (S)-2-amino-1-phenylethanol and (R)-2-amino-1-phenylethanol with L and D glutamic acid. Biological studies revealed that two isomers showed potent antioxidant activity. Among these two, the most
Jeevan,Umashankara,Kumar, Y.C. Sunil,Kumara,Rangappa
p. 927 - 932
(2018/03/13)

α-ZrP/Uracil/Cu2+ nanoparticles as an efficient catalyst in the Morita-Baylis-Hillman reaction
A facile synthesis of uracil-Cu2+ nanoparticles immobilized on alpha-zirconium hydrogen phosphate (α-ZrP), abbreviated as α-ZrP/Uracil/Cu2+, was presented. This compound was synthesized by the thermal method and used as a reusable ca
Hajipour, Abdol R.,Zakery, Saedeh
(2018/09/06)

Hemilability-Driven Water Activation: A NiII Catalyst for Base-Free Hydration of Nitriles to Amides
The NiII complex 1 containing pyridyl- and hydroxy-functionalized N-heterocyclic carbenes (NHCs) is synthesized and its catalytic utility for the selective nitrile hydration to the corresponding amide under base-free conditions is evaluated. The title compound exploits a hemilabile pyridyl unit to interact with a catalytically relevant water molecule through hydrogen-bonding and promotes a nucleophilic water attack to the nitrile. A wide variety of nitriles is hydrated to the corresponding amides including the pharmaceutical drugs rufinamide, Rifater, and piracetam. Synthetically challenging α-hydroxyamides are accessed from cyanohydrins under neutral conditions. Related catalysts that lack the pyridyl unit (i.e., compounds 2 and 4) are not active whereas those containing both the pyridyl and the hydroxy or only the pyridyl pendant (i.e., compounds 1 and 3) show substantial activity. The linkage isomer 1′ where the hydroxy group is bound to the metal instead of the pyridyl group was isolated under different crystallization conditions insinuating a ligand hemilabile behavior. Additional pKa measurements reveal an accessible pyridyl unit under the catalytic conditions. Kinetic studies support a ligand-promoted nucleophilic water addition to a metal-bound nitrile group. This work reports a Ni-based catalyst that exhibits functional hemilability for hydration chemistry.
Singh, Kuldeep,Sarbajna, Abir,Dutta, Indranil,Pandey, Pragati,Bera, Jitendra K.
p. 7761 - 7771
(2017/06/06)

Condensation of vilsmeier salts, derived from tetraalkylureas, with α-hydroxy amide derivatives: One-pot approach to synthesize 2-dialkylamino-2-oxazolin-4-ones
A novel and straightforward synthetic protocol was developed to synthesize 2-dialkylamino-2-oxazolin-4-ones from various Vilsmeier salts and α-hydroxy amides derivatives. Notably, thozalinone (3a), as a mild stimulant in tristimania and anorexic, could be synthesized simply and in a high yield using this methodology.
Liu, Bengen,Su, Dongshan,Wei, Zhonglin,Cao, Jungang,Liang, Dapeng,Lin, Yingjie,Duan, Haifeng
supporting information
p. 249 - 252
(2017/02/10)

SUBSTITUTED PYRIDINES AS INHIBITORS OF DNMT1
The invention is directed to substituted pyridine derivatives. Specifically, the invention is directed to compounds according to Formula (Iar): (Iar) wherein Yar, X1ar, X2ar, R1ar, R2ar, R3ar, R4ar and R5ar are as defined herein; or a pharmaceutically acceptable salt or prodrug thereof. The compounds of the invention are selective inhibitors of DNMT1 and can be useful in the treatment of cancer, pre-cancerous syndromes, beta hemoglobinopathy disorders, sickle cell disease, sickle cell anemia, and beta thalassemia, and diseases associated with DNMT1 inhibition. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting DNMT1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
-
Page/Page column 536

(2018/01/20)

HPLC enantioseparation on a homochiral MOF-silica composite as a novel chiral stationary phase
The last frontier in the development of chiral stationary phases for chromatographic enantioseparation involves homochiral metal-organic frameworks (MOFs). Using enantiopure (R)-2,2′-dihydroxy-1,1′-binaphthalene-6,6′-dicarboxylic acid as a starting material, we prepared three homochiral MOFs that were further used as chiral stationary phases for high-performance liquid chromatography to separate the enantiomers of various kinds of racemic sulfoxides, sec-alcohols, β-lactams, benzoins, flavanones and epoxides. The experimental results showed excellent performances for enantioseparation, and highlighted that enantioseparation on homochiral MOF columns is practical.
Tanaka, Koichi,Muraoka, Toshihide,Otubo, Yasuhiro,Takahashi, Hiroki,Ohnishi, Atsushi
p. 21293 - 21301
(2016/03/08)

Generation and Reaction of Carbamoyl Anions in Flow: Applications in the Three-Component Synthesis of Functionalized α-Ketoamides
Using a flow microreactor system, carbamoyllithium compounds were successfully generated and used for reactions with electrophiles to give various amides, including α-ketoamides. The present method could be applied to the three-component synthesis of functionalized α-ketoamides using a carbamoyllithium compound, methyl chloroformate, and a functionalized organolithium reagent. Go with the flow: Using a flow microreactor system, carbamoyllithium compounds were successfully generated and used to react with electrophiles to give various amides, including α-ketoamides. The method was applied to the three-component synthesis of functionalized α-ketoamides using a carbamoyllithium compound, methyl chloroformate, and a functionalized organolithium reagent. PMB=p-methoxybenzyl; FG=functional group.
Nagaki, Aiichiro,Takahashi, Yusuke,Yoshida, Jun-Ichi
p. 5327 - 5331
(2016/04/26)

Substrate evaluation of rhodococcus erythropolis SET1, a nitrile hydrolysing bacterium, demonstrating dual activity strongly dependent on nitrile sub-structure
Assessment of Rhodococcus erythropolis SET1, a novel nitrile hydrolysing bacterial isolate, has been undertaken with 34 nitriles, 33 chiral and 1 prochiral. These substrates consist primarily of β-hydroxy nitriles with varying alkyl and aryl groups at the β position and containing in several compounds different substituents α to the nitrile. In the case of β-hydroxy nitriles without substitution at the α position, acids were the major products obtained, along with recovered nitrile after biotransformation, as a result of suspected nitrilase activity of the isolate. Unexpectedly, amides were found to be the major hydrolysis product when the β-hydroxy nitriles possessed a vinyl group at this position. To probe this behaviour further, additional related substrates were evaluated containing electron-withdrawing groups at the α position, and amide was also observed upon biotransformation in the presence of SET1. Therefore this novel isolate has also demonstrated NHase activity with nitriles that appears to be substrate-dependent.
Coady, Tracey M.,Coffey, Lee V.,O'Reilly, Catherine,Lennon, Claire M.
supporting information
p. 1108 - 1116
(2015/02/19)

Asymmetric ammonolysis of (R/S)-mandelic acid by immobilized lipases via direct amidation of mandelic acid in biphasic media
We have investigated the direct enantioselective amidation of mandelic acid with ammonia, catalyzed by a variety of commercial lipases including those from Candida rugosa, Mucor miehei, Pseudomonas sp., Rhizomucor miehei, and Thermomyces lanuginosus coval
Yildirim, Deniz,Tükel, S. Seyhan
p. 251 - 258
(2015/02/02)

Characterization of an enantioselective amidase from Cupriavidus sp. KNK-J915 (FERM BP-10739) useful for enzymatic resolution of racemic 3-piperidinecarboxamide
A novel amidase (CsAM) acting on (R,S)-N-benzyl-3-piperidinecarboxamide was purified from Cupriavidus sp. KNK-J915 (FERM BP-10739) and characterized. The enzyme acts on (R,S)-N-benzyl-3-piperidinecarboxamide S-selectively to yield (R)-N-benzyl-3-piperidinecarboxamide. Analytical gel filtration column chromatography and SDS-PAGE revealed that the enzyme is a tetramer with a subunit of approximately 47 kDa. It has a broad substrate spectrum against nitrogen-containing heterocyclic amides. Its optimal pH and temperature are 8.0-9.0 and 50 °C, respectively. The CsAM gene was cloned and sequenced, and it was found to comprise 1341 bp and encode a polypeptide of 46,388 Da. The deduced amino acid sequence exhibited 78% identity to that of a putative amidase (CnAM) from Cupriavidus necator JMP134. The cultured cells of recombinant Escherichia coli producing CnAM could be used for the S-selective hydrolysis of (R,S)-N-benzyl-3-piperidinecarboxamide but could not be used for the S-selective hydrolysis of (R,S)-3-piperidinecarboxamide because of its very low level of selectivity. In contrast, the cultured cells of recombinant E. coli producing CsAM could hydrolyze both (R,S)-N-benzyl-3-piperidinecarboxamide and (R,S)-3-piperidinecarboxamide with high S-selectivity.
Nojiri, Masutoshi,Taoka, Naoaki,Yasohara, Yoshihiko
p. 136 - 142
(2014/12/10)

Mechanistic investigations and secondary coordination sphere effects in the hydration of nitriles with [Ru(η6-arene)Cl2PR 3] complexes
The mechanism of the nitrile-to-amide hydration reaction using [Ru(η6-arene)Cl2(PR3)] complexes as catalysts was investigated (η6-arene = C6H 6, p-cymene, C6Me6; R = NMe2, OMe, OEt, Et, iPr). Experiments showed that the mechanism involves the following general sequence of reactions: substitution of a chloride ligand by the nitrile substrate, intermolecular nucleophilic attack by water to form an amidate intermediate, and dissociation of the resulting amide. The effects of secondary coordination sphere interactions on the rates and yields of the hydration reaction were investigated. Ligands that are capable of acting as hydrogen bond acceptors with the entering water molecule result in faster rates and higher yields than non-hydrogen-bonding ligands. The faster rates are attributable to the H-bonding-facilitated deprotonation of the water as the oxygen of the water bonds to the coordinated nitrile. DFT calculations on the proposed H-bonding intermediates support this interpretation. Most homogeneous catalysts will not hydrate cyanohydrins because of the equilibrium amounts of cyanide that are present in solutions of cyanohydrins; the cyanide poisons the catalyst. Because of its increased catalytic reactivity due to secondary coordination sphere effects, the [Ru(η6-arene)Cl2(P(NMe2) 3)] catalyst gives significant yields of cyanohydrin hydration products with glycolonitrile, lactonitrile, acetone cyanohydrin, and mandelonitrile. A Taft plot showed that an increase in the steric bulk of the nitrile results in a decrease in the hydration rate, and a Hammett plot showed that electron-withdrawing groups facilitate nitrile hydration. The decrease in rate as the size of the cyanohydrin increases is likely due to both increased steric bulk and to the addition of electron-donating groups on the nitrile. The [Ru(η6-arene)Cl2(PR3)] catalysts are initially less susceptible to cyanide poisoning than other homogeneous nitrile hydration catalysts because [Ru(η6-p-cymene)(CN)(Cl)(P(NMe 2)3)] forms in the presence of cyanide. The electron-withdrawing cyanide ligand facilitates nucleophilic attack of water on a coordinated nitrile in this molecule.
Knapp, Spring Melody M.,Sherbow, Tobias J.,Yelle, Robert B.,Zakharov, Lev N.,Juliette, J. Jerrick,Tyler, David R.
supporting information
p. 824 - 834
(2013/03/28)

The combi-CLEA approach: Enzymatic cascade synthesis of enantiomerically pure (S)-mandelic acid
Enantiomerically pure (S)-mandelic acid was synthesised from benzaldehyde by sequential hydrocyanation and hydrolysis in a bienzymatic cascade at starting concentrations up to 0.25 M. A cross-linked enzyme aggregate (CLEA) composed of the (S)-selective oxynitrilase from Manihot esculenta and the non-selective nitrilase from Pseudomonas fluorescens EBC 191 was employed as the biocatalyst. The nitrilase produces approx. equal amounts of (S)-mandelic acid and (S)-mandelic amide from (S)-mandelonitrile under standard conditions, but we surprisingly found that high (up to 0.5 M) concentrations of HCN induced a marked drift towards amide production. By including the amidase from Rhodococcus erythopolis in the CLEA we obtained (S)-mandelic acid as the sole product in 90% yield and >99% enantiomeric purity.
Chmura, Andrzej,Rustler, Sven,Paravidino, Monica,Van Rantwijk, Fred,Stolz, Andreas,Sheldon, Roger A.
p. 1225 - 1232
(2013/10/22)

Production of L-tryptophan by enantioselective hydrolysis of d,l-tryptophanamide using a newly isolated bacterium
Bacterial strain ZJB-09211 capable of amidase production has recently been isolated from soil samples. The strain is able to asymmetrically hydrolyze l-tryptophanamide from d,l-tryptophanamide to produce l-tryptophan in high yield and with excellent stereoselectivity (enantiomeric excess > 99.9 %, and enantiomeric ratio > 200). Strain ZJB-09211 has been identified as Flavobacterium aquatile based on the cell morphology analysis, physiological tests, and the 16S rDNA sequence analysis. Optimization of the fermentation medium led to an about six-fold increase in the amidase activity of strain ZJB-09211, which reached 501.5 U L-1. Substrate specifity and stereoselectivity investigations revealed that amidase of F. aquatile possessed a broad substrate spectrum and high enantioselectivity.
Xu, Jian-Miao,Chen, Ben,Wang, Yuan-Shan,Zheng, Yu-Guo
p. 1262 - 1270
(2013/07/19)

Influence of point mutations near the active site on the catalytic properties of fungal arylacetonitrilases from Aspergillus niger and Neurospora crassa
Arylacetonitrilases from Aspergillus niger CBS 513.88 and Neurospora crassa OR74A (NitAn and NicNc, respectively) were expressed in recombinant Escherichia coli JM109. The respective whole-cell catalysts preferentially hydrolyzed (R)-enantiomers of (R,S)-mandelonitrile and (R,S)-2-phenylpropionitrile. NitNc also formed significant amounts of mandelamide from (R,S)-mandelonitrile (40% of total product), mainly found as the (S)-enantiomer. At pH 4.5 and 5.0, the cells retained more than 40 and 60% of their nitrilase activity at pH 7, respectively. Nitrilase variants generated by site-directed mutagenesis carried amino acid replacements in the vicinity of the catalytically active cysteine residues (C162 and C167 in NitAn and NitNc, respectively). The conversions of (R,S)-mandelonitrile and (R,S)-2-phenylpropionitrile by the nitrilase variants were compared to the wild-type nitrilases in terms of activity, enantioselectivity, and acid/amide ratio of the products formed. Thus the W168A variant of NitNc was identified, which formed significantly increased amounts of mandelamide and 2-phenylpropionamide, and which demonstrated an almost complete inversion of enantioselectivity for the conversion of (R,S)-2- phenylpropionitrile (from R- to S-selectivity).
Petrickova, Alena,Sosedov, Olga,Baum, Stefanie,Stolz, Andreas,Martinkova, Ludmila
experimental part
p. 74 - 80
(2012/06/29)

Application of a recombinant Escherichia coli whole-cell catalyst expressing hydroxynitrile lyase and nitrilase activities in ionic liquids for the production of (S)-mandelic acid and (S)-mandeloamide
The conversion of benzaldehyde and cyanide into mandelic acid and mandeloamide by a recombinant Escherichia coli strain which simultaneously expressed an (S)-hydroxynitrile lyase (oxynitrilase) from cassava (Manihot esculenta) and an aryl-acetonitrilase from Pseudomonas fluorescens EBC191 was studied. Benzaldehyde exhibited a pronounced inhibitory effect on the nitrilase activity in concentrations ≥25 mM. Therefore, it was tested if two-phase systems consisting of a buffered aqueous phase and the ionic liquid 1-butyl-1-pyrrolidinium bis(trifluoromethanesulfonyl)imide (BMpl NTf 2) or 1-butyl-3-methylimidazolium hexafluorophosphate (BMim PF 6) could be used for the intended biotransformation. The distribution coefficients of the substrates, intermediates and products of the reaction were determined and it was found that BMpl NTf2 and BMim PF6 were highly efficient as substrate reservoirs for benzaldehyde. The recombinant E. coli strain was active in the presence of BMpl NTf2 or BMim PF6 phases and converted benzaldehyde and cyanide into mandelic acid and mandeloamide. The two-phase systems allowed the conversion of benzaldehyde dissolved in the ionic liquids to a concentration of 700 mM with product yields (=sum of mandelic acid and mandeloamide) of 87-100%. The cells were slightly more effective in the presence of BMpl NTf2 than in the presence of BMim PF6. In both two-phase systems benzaldehyde and cyanide were converted into (S)-mandeloamide and (S)-mandelic acid with enantiomeric excesses ≥94%. The recombinant E. coli cells formed, in the two-phase systems with ionic liquids and increased substrate concentrations, higher relative amounts of mandelo-amide than in a purely aqueous system with lower substrate concentrations.
Baum, Stefanie,Van Rantwijk, Fred,Stolz, Andreas
experimental part
p. 113 - 122
(2012/04/10)

Biocatalytic reduction of α-keto amides to (R)-α-hydroxy amides using Candida parapsilosis ATCC 7330
Biocatalytic reduction of primary and secondary α-keto amides was accomplished using whole cells of Candida parapsilosis ATCC 7330. The primary (R)-α-hydroxy amides were obtained in good enantiomeric excess (up to 94%) and conversion (88-99%) as compared to the secondary (R)-α-hydroxy amides.
Stella, Selvaraj,Chadha, Anju
p. 345 - 352
(2013/01/15)

PROCESS FOR PRODUCING ORGANIC CARBOXYLIC ACID AMIDES
The present invention relates to a process for producing organic carboxylic acid amides by nitrile hydrolysis of a nitrile compound at certain temperature and pressure in the presence of a catalyst to produce an organic carboxylic acid amide.
-
Page/Page column 5

(2011/01/12)

Probing the enantioselectivity of a diverse group of purified cobalt-centred nitrile hydratases
In this study a diverse range of purified cobalt containing nitrile hydratases (NHases, EC 4.2.1.84) from Rhodopseudomonas palustris HaA2 (HaA2), Rhodopseudomonas palustris CGA009 (009), Sinorhizobium meliloti 1021 (1021), and Nitriliruptor alkaliphilus (iso2), were screened for the first time for their enantioselectivity towards a broad range of chiral nitriles. Enantiomeric ratios of >100 were found for the NHases from HaA2 and CGA009 on 2-phenylpropionitrile. In contrast, the Fe-containing NHase from the well-characterized Rhodococcus erythropolis AJ270 (AJ270) was practically aselective with a range of different α-phenylacetonitriles. In general, at least one bulky group in close proximity to the α-position of the chiral nitriles seemed to be necessary for enantioselectivity with all NHases tested. Nitrile groups attached to a quaternary carbon atom were only reluctantly accepted and showed no selectivity. Enantiomeric ratios of 80 and >100 for AJ270 and iso2, respectively, were found for the pharmaceutical intermediate naproxennitrile, and 3-(1-cyanoethyl)benzoic acid was hydrated to the corresponding amide by iso2 with an enantiomeric ratio of >100.
Van Pelt,Zhang,Otten,Holt,Sorokin,Van Rantwijk,Black,Perry,Sheldon
experimental part
p. 3011 - 3019
(2011/06/17)

Construction of Recombinant Escherichia coli catalysts which simultaneously express an (S)-oxynitrilase and different nitrilase variants for the synthesis of (S)-mandelic acid and (S)-mandelic amide from benzaldehyde and cyanide
Recombinant Escherichia coli strains were constructed which simultaneously expressed the genes encoding the (S)-oxynitrilase from cassava (Manihot esculenta) together with the wild-type or a mutant variant of the arylacetonitrilase from Pseudomonas fluorescens EBC191 in a single organism under the control of a rhamnose-inducible promoter. The whole cell catalysts obtained converted benzaldehyde and potassium cyanide in aqueous media at pH 5.2 mainly to (S)-mandelic acid and/or (S)-mandelic amide and synthesized only low amounts of the corresponding (R)-enantiomers. The conversion of benzaldehyde and potassium cyanide (KCN) by a whole-cell catalyst simultaneously expressing the (5)-oxynitrilase and the wild-type nitrilase resulted in a ratio of (S)-mandelic acid to (S)-mandelic amide of about 4:3. This could be explained by the strong nitrile hydratase activity of the wild-type nitrilase with (S)-mandelonitrile as substrate. The relative proportion of (S)-mandelic amide formed in this system was significantly increased by coexpressing the (S)-oxynitrilase with a carboxy-terminally truncated variant of the nitrilase. This whole-cell catalyst converted benzaldehyde and KCN to mandelic amide and mandelic acid in a ratio of about 9:1. The ee of the (S)-mandelic amide formed was calculated to be 95%.
Sosedov, Olga,Matzer, Kathrin,Buerger, Sibylle,Kiziak, Christoph,Baum, Stefanie,Altenbuchner, Josef,Chmura, Andrzej,Van Rantwijk, Fed,Stolz, Andreas
body text
p. 1531 - 1538
(2011/03/22)

Enantioselective conversion of α-arylnitriles by Klebsiella oxytoca
A new bacterial isolate Klebsiella oxytoca 38.1.2 with stereoselective nitrile hydratase activity against rac-2-phenylglycine nitrile, rac-2-phenylpropionitrile and rac-mandelonitrile was investigated. The cultivation conditions for growth and nitrile hydratase formation were studied. An intracellular (S)-enantioselective nitrile hydratase and a putative (S)-selective amidase were found to be induced in the presence of rac-2-phenylpropionitrile. The temperature dependence on the enantioselectivity of the nitrile hydratase active cells was studied in more detail for the biotransformation of rac-2-phenylpropionitrile and rac-mandelonitrile. By increasing the temperature from 15 °C to 37 °C, the apparent enantiomeric ratio of the conversion of rac-2-phenylpropionitrile to (S)-2-phenylpropionamide increased from 16 to 35 at nearly 50% conversion rate. rac-Mandelonitrile was converted to (S)-mandelamide with an enantiomeric excess of up to 95% in a 80% yield without further conversion to mandelic acid.
Ewert, Christian,Lutz-Wahl, Sabine,Fischer, Lutz
body text
p. 2573 - 2578
(2009/04/06)

Asymmetric tosylation of racemic 2-hydroxyalkanamides with chiral copper catalyst
Kinetic resolution of 2-hydroxyalkanamides was performed by tosylation in the presence of copper(II) triflate and (R,R)-Ph-BOX as a catalyst. This method was successfully applied to a variety of 2-hydroxyalkanamides in high enantioselectivity with up to 9
Onomura, Osamu,Mitsuda, Masaru,Nguyen, My Thi Thuy,Demizu, Yosuke
p. 9080 - 9084
(2008/03/27)

Enzyme stabilizer DTT catalyzes nitrilase analogue hydrolysis of nitriles
Amides are the dominating products in some nitrilase catalyzed conversions of α-activated nitriles, but unexpectedly this hydrolytic reaction is also catalyzed by 1,4-dithio-dl-threitol (DTT), a standard antioxidizing enzyme stabilizer. The Royal Society
Winkler, Margit,Glieder, Anton,Klempier, Norbert
p. 1298 - 1300
(2008/02/03)

Synthesis of enantiomerically pure (S)-mandelic acid using an oxynitrilase-nitrilase bienzymatic cascade: A nitrilase surprisingly shows nitrile hydratase activity
Benzaldehyde was converted into enantiomerically pure (S)-mandelic acid by sequential HCN addition and hydrolysis in the presence of a cross-linked enzyme aggregate composed of the (S)-selective oxynitrilase from Manihot esculenta and the non-selective recombinant nitrilase from Pseudomonas fluorescens EBC 191. Surprisingly, (S)-mandelic amide was formed in large amounts. It was shown, in separate experiments, that the nitrilase hydrolyses (S)-mandelonitrile into an approx. equimolar mixture of acid and amide, whereas with the (R)-enantiomer only 10% of amide was formed.
Mateo, Cesar,Chmura, Andrzej,Rustler, Sven,Van Rantwijk, Fred,Stolz, Andreas,Sheldon, Roger A.
p. 320 - 323
(2007/10/03)

Nitrile hydratase activity of a recombinant nitrilase
Appreciable amounts of amide are formed in the course of nitrile hydrolysis in the presence of recombinant nitrilase from Pseudomonas fluorescens EBC 191, depending on the α-substituent and the reaction conditions. The ratio of the nitrilase and nitrile hydratase activities of the enzyme is profoundly influenced by the electronic and steric properties of the reactant. In general, amide formation increased when the α-substituent was electron-deficient; 2-chloro-2-phenylacetonitrile, for example, afforded 89% amide. We found, moreover, that (R)-mandelo-nitrile was hydrolysed with 11% of amide formation whereas 55% amide was formed from the (S)-enantiomer; a similar effect was found for the O-acetyl derivatives. A mechanism that accomodates our results is proposed.
Fernandes, Bruno C. M.,Mateo, Cesar,Kiziak, Christoph,Chmura, Andrzej,Wacker, Jan,Van Rantwijk, Fred,Stolz, Andreas,Sheldon, Roger A.
p. 2597 - 2603
(2007/10/03)

Enantioselective homoallyl-cyclopropanation of dibenzylideneacetone by modified allylindium halide reagents-rapid access to enantioenriched 1-styryl-norcarene
Dibenzylideneacetone (8) reacts with in situ-generated allylindium halide reagents to yield the product of a homoallyl-cyclopropanation reaction: 2-(3″-butenyl)-1,1-bis[(E)-2′-phenylethenyl]cyclopropane (9), which proceeds via step-wise cleavage of the C{double bond, long}O bond and delivery of two allyl fragments from the reagent. A range of enantiomerically enriched ligands have been tested as stoichiometric asymmetric modifiers for this process. Enantiopure compounds such as cinchona alkaloids, ephedra, aminoalcohols and tartaric acid derivatives, which have proven of utility as asymmetric modifiers for the indium-mediated allylation of aldehydes and ketones, were very inefficient in the process 8→9. However, mandelic acid derivatives, in particular mandelates, were found to be of significant potential. The absolute stereochemistry of the cyclopropane 9 has been determined by degradation to 1,1-dicarboxymethyl-2-butylcyclopropane, converging with an independent enantioselective synthesis starting from hexene. Under optimised conditions, viz. using allylindium iodide reagents and working-up with aqueous Na2SO3 to avoid iodine-mediated polymerisation, (S)-9 can be generated in 86% yield and with (S)-methyl mandelate as modifier useful enantiopurity (94/6 er) was observed. The cyclopropane product ((S)-9) undergoes RCM using standard conditions to afford a norcarene unit ((1S,6S)-1-(E)-2′-(phenylethenyl)-bicyclo[4.1.0]hept-2-ene) without loss of enantiopurity.
Lloyd-Jones, Guy C.,Wall, Philip D.,Slaughter, Jennifer L.,Parker, Alexandra J.,Laffan, David P.
p. 11402 - 11412
(2007/10/03)

Remote chiral induction in the organocatalytic hydrosilylation of aromatic ketones and ketimines
(Chemical Equation Presented) Lewis basic, metal-free pyridyloxazolines catalyze the reduction of prochiral aromatic ketones and ketimines with Cl 3SiH in good enantioselectivity (up to 94% ee). Arene-arene interactions between the substrate and the catalyst are likely to play a role in the enantiodifferentiation process.
Malkov, Andrei V.,Stewart Liddon, Angus J. P.,Ramirez-Lopez, Pedro,Bendova, Lada,Haigh, David,Kocovsky, Pavel
p. 1432 - 1435
(2007/10/03)

Generation of carbamoyl- and thiocarbamoyllithium synthons having a hydrogen(s) or an aryl group on the nitrogen and their trapping with carbonyl electrophiles
Dimetalated amides 1 (Y = O) were generated as the synthons of carbamoyllithiums 2 (Y = O) by the reaction of isocyanates with iBu2AlTenBu and a subsequent tellurium-lithium exchange reaction. A series of amide derivatives
Kambe, Nobuaki,Inoue, Toru,Takeda, Takanobu,Fujiwara, Shin-Ichi,Sonoda, Noboru
p. 12650 - 12651
(2008/02/05)

Efficient method for the direct preparation of amides from carboxylic acids using tosyl chloride under solvent-free conditions
A simple, clean and highly efficient solvent-free procedure for the preparation of primary, secondary, tertiary and aromatic amides is described from the direct reaction of carboxylic acids and silica-supported ammonium salts, triethylamine (TEA) and tosyl chloride (TsCl) as condensing agent. The reaction proceeds rapidly in high yields at room temperature.
Khalafi-Nezhad, Ali,Parhami, Abolfath,Soltani Rad, Mohammad Navid,Zarea, Abdolkarim
p. 6879 - 6882
(2007/10/03)

Remote stereocontrol mediated by the sulfinyl group: Hydrocyanation of 2-p-tolylsulfinyl benzaldehyde
Enantiomerically pure cyanohydrins derived from 2-p-tolylsulfinyl benzaldehyde can be obtained by reaction with different hydrocyanating reagents in the presence of Yb(OTf)3 or Y(OTf)3.
Garcia Ruano, Jose Luis,Martin-Castro, Ana M.,Tato, Francisco,Cardenas, Diego J.
p. 1963 - 1968
(2007/10/03)

Method for producing optically active mandelamide derivative and optically active phenylethanolamine derivative
[PROBLEM TO BE SOLVED]: Though optically active mandelamide derivative and optically active phenylethanolamine derivative are useful as agrochemical intermediate,the conventional manufacturing method of them has a lot of problems. Consequently, the develo
-
Page/Page column 9

(2008/06/13)

Facial-selective allylation of methyl ketones for the asymmetric synthesis of tertiary homoallylic ethers
The stereoselective allylation of methyl ketones is described to give tertiary homoallylic ethers, which can easily be transformed into homoallylic alcohols by a Birch reduction. Reaction of methyl ketones 4 with allylsilane 5 in the presence of the chiral TMS ether 3a and a catalytic amount of trifluoromethanesulfonic acid led to homoallylic ethers 6 in high yield with a selectivity of 9:1 to >20:1. The TMS ether 3a was prepared from inexpensive mandelic acid, which is commercially available in both enantiomeric forms, in four steps.
Tietze, Lutz F.,Hoelsken, Soeren,Adrio, Jens,Kinzel, Tom,Wegner, Christoph
p. 2236 - 2239
(2007/10/03)

TETRAHYDROISOQUINOLYL ACETAMIDE DERIVATIVES FOR USE AS OREXIN RECEPTOR ANTAGONISTS
The invention relates to novel acetamide derivatives of formula (I) and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of such compound
-
Page 72

(2008/06/13)

The mandelamide keto-enol system in aqueous solution. Generation of the enol by hydration of phenylcarbamoylcarbene
Flash photolysis of diazophenylacetamide in aqueous solution produced phenylcarbamoylcarbene, whose hydration generated a transient species that was identified as the enol isomer of mandelamide. This assignment is based on product identification and the shape of the rate profile for decay of the enol transient, through ketonization to its carbonyl isomer, as well as by the form of acid - base catalysis of and solvent isotope effects on the decay reaction. Rates of enolization of mandelamide were also determined, by monitoring hydrogen exchange at its benzylic position, and these, in combination with the ketonization rate measurements, gave the keto - enol equilibrium constant pKE = 15.88, the acidity constant of the enol ionizing as an oxygen acid, pQaE = 8.40, and the acidity constant of the amide ionizing as a carbon acid pQaK = 24.29. (These acidity constants are concentration quotients applicable at ionic strength = 0.10 M.) These results show the enol content and carbon acid strength of mandelamide, like those of mandelic acid and methyl mandelate, to be orders of magnitude less than those of simple aldehydes and ketones; this difference can be attributed to resonance stabilization of the keto isomers of mandelic acid and its ester and amide derivatives, through electron delocalization into their carbonyl groups from the oxygen and nitrogen substituents adjacent to these groups. The enol of mandelamide, on the other hand, again like the enols of mandelic acid and methyl mandelate, is a substantially stronger acid than the enols of simple aldehydes and ketones. This difference can be attributed to the electronegative nature of the oxygen and nitrogen substituents geminal to the enol hydroxyl group in the enols of mandelic acid and its derivatives; in support of this, the acidity constants of these enols correlate well with field substituent constants of these geminal groups.
Chiang,Guo,Kresge,Richard,Toth
p. 187 - 194
(2007/10/03)

Kinetics and mechanism of acid-catalyzed hydrolysis of the diazo functional group of diazophenylacetamide
The acid-catalyzed hydrolysis of diazophenylacetamide giving mandelamide as product was found to occur with a normal (kH/kD > 1) hydronium ion isotope effect and to be subject to general acid rather than specific hydronium ion catalysis. This shows that the reaction occurs by rat e-determining hydron transfer from the catalyzing acid to the diazo carbon atom of the substrate, followed by rapid displacement of the diazo group by water. Comparison of the rate of this reaction with those of the same process for other diazophenylacetic acid functional derivatives, PhCN2COX, reveals that the reactivity of these substrates is controlled by the electron-releasing resonance ability of the group X. Copyright
Chang,Kresge
p. 598 - 602
(2007/10/03)

Chemo-enzymatic synthesis of enantiomerically pure (R)-2-naphthylmethoxyacetic acid
Enantiomerically pure (R)-2-naphthylmethoxyacetic acid (2-NMA) was synthesized from 2-naphthaldehyde via an integrated chemo-enzymatic procedure. The one-pot, successive use of SnBr2-TMSCN and AcBr worked effectively to give a racemic cyanohydrin acetate. Lipase from Burkholderia cepacia then mediated the highly enantioselective hydrolysis of the (S)-enantiomer of the racemate, leaving the (R)-acetate with an e.e. of >99.9%. The resulting product of this enzyme-catalyzed hydrolysis, an (S)-cyanohydrin, spontaneously decomposed into naphthaldehyde, the starting material of this synthetic route, which could be recycled. The hydration of nitrile to amide as well as the hydrolysis of the acetate was performed with a microorganism, Rhodococcus rhodochrous, under very mild conditions without any loss of the enantiomeric purity. The amide group was hydrolyzed with nitrosylsulfuric acid, and the product was isolated as an α-hydroxy ester. The α-hydroxyl group was methylated with diazomethane-silica gel and the final task, hydrolysis of the ester, was accomplished under conditions as mild as neutral pH with an esterase from Krebsiella oxytoca to give enantiomerically pure 2-NMA.
Kimura, Mayumi,Kuboki, Atsuhito,Sugai, Takeshi
p. 1059 - 1068
(2007/10/03)

Synthesis of O-protected mandelamide and its elaboration to 5-hydroxy-1,5-diphenylhydantoin
-
Papakyprianou,Parkins,Prince,Steed
p. 436 - 440
(2007/10/03)

1,1′-Binaphthylazepine-based ligands for asymmetric catalysis. Part 1: Preparation and characterization of some new aminoalcohols and diamines
Starting from (S)-1,1′-binaphthol, a series of ten novel enantiopure 1,1′-binaphthylazepine-based aminoalcohols and diamines 1a-1j were efficiently prepared and fully characterized. These derivatives, having either only an atropisomeric bridged-binaphthyl backbone or an additional stereogenic carbon center, can be interesting ligands for asymmetric catalysis.
Mecca, Tommaso,Superchi, Stefano,Giorgio, Egidio,Rosini, Carlo
p. 1225 - 1233
(2007/10/03)

Efficient synthesis of primary amides using 2-mercaptopyridone-1-oxide-based uronium salts
S-(1-Oxido-2-pyridinyl)-1,1,3,3-tetramethylthiouronium tetrafluoroborate (TOTT) and hexafluorophosphate (HOTT) are cheap and convenient reagents for the rapid and high-yielding preparation of primary amides when reacted with carboxylic acids and ammonium chloride in the presence of diisopropylethylamine. The reaction is chemoselective and undesired ammonolysis of other sensitive functional groups is not observed. (C) 2000 Elsevier Science Ltd.
Bailen,Chinchilla,Dodsworth,Najera
p. 9809 - 9813
(2007/10/03)

Process for preparing free alpha -hydroxy acids from ammonium salts thereof
PCT No. PCT/JP97/00528 Sec. 371 Date Aug. 25, 1998 Sec. 102(e) Date Aug. 25, 1998 PCT Filed Feb. 25, 1997 PCT Pub. No. WO97/30962 PCT Pub. Date Aug. 28, 1997A process for preparing alpha -hydroxy acids by heating ammonium salts of alpha -hydroxy acids of
-
(2008/06/13)

Controlled racemization and asymmetric transformation of α-substituted carboxylic acids in the melt
The racemization and asymmetric transformation of a series of α- substituted carboxylic acids, viz. mandelic acid, hydratropic acid, ibuprofen and naproxen, were studied. Several racemization methods for mandelic acid were studied and it was found that base-catalyzed racemization in aprotic polar solvents was the most efficient method. Moreover, a fast and mild base- catalyzed racemization reaction in the melt was developed. DBN turned out to be a very efficient racemizing base for the substrates studied. Combination of the base-catalyzed racemization in the melt with known resolution processes resulted in crystallization-induced asymmetric transformations. Treating racemic ibuprofen or hydratropic acid with 1.5-2.5 equivalents of enantiopure α-methylbenzylamine and a catalytic amount of DBN resulted in the isolation of enantiomerically enriched ibuprofen or hydratropic acid with ees of up to 75% and almost quantitative yields.
Ebbers, Eelco J.,Ariaans, Gerry J. A.,Bruggink, Alle,Zwanenburg, Binne
p. 3701 - 3718
(2007/10/03)

OCCURENCE OF THE CYANOGENIC GLUCOSIDE PRUNASIN AND ITS CORRESPONDING MANDELIC ACID AMIDE GLUCOSIDE IN OLINIA SPECIES (OLINIACEAE)
The cyanogenic glucoside prunasin (2-β-D-glucopyranosyloxy-2-phenylacetonitrile) was isolated from leaves and twigs of Olinia emarginata.It was also identified and quantified in leaves and stemp of O. ventosa, O. radiata and O. rochetiana.The correspondin
Nahrstedt, Adolf,Rockenbach, Juergen
p. 433 - 436
(2007/10/02)

Process for the preparation of phenylethanolaminotetralins
A process for the preparation of phenylethanolaminotetralins of formula STR1 wherein X is hydrogen, a halogen, a trifluoromethyl or a lower alkyl group and R° is hydrogen or a methyl group substituted by a carboxy or a lower carbalkoxy group, which compri
-
(2008/06/13)

Enantioselective synthesis of (R)-(-)-1-phenylethanolamines using Baker's yeast reduction of some α-substituted methyl phenyl ketones
The Baker's yeast reductions of α-chloroacetophenone, α-azidoacetophenone and 2-oxo-2-phenylacetamide are used as key steps in the preparation of optically active (R)-(-)-1-phenylethanolamines.
Brenelli, Eugenia C S,Carvalho, Marcia de,Okubo, Marina T,Marques, Margarete,Moran, Paulo J S,et al.
p. 821 - 823
(2007/10/02)

Pyridine compounds which are useful in treating a disease state characterized by an excess of platelet activating factors
The invention relates to compounds of the formula STR1 wherein Y and Y' are hydrogen or taken together are O or S, *A is paraphenylene or *----(CH2)n --(X)s --(CH2)r ----, X is O, S or --CH=CH--, n or r, independently, are integers from 0 to 3, m is an integer from 0 to 1, s is an integer from 0 to 1, provided that when s is 1, n+m must be at least 2, t is an integer from 0 to 10, R1 and R2, independently, are lower alkyl, lower alkenyl or aryl, or one of R1 or R2 is hydrogen and the other is STR2 wherein W is STR3 --CH2 --CH2 --, --CH2 --, O, S, or STR4 and X1 is lower alkyl, phenyl unsubstituted or mono-, di- or trisubstituted by lower alkoxy, lower alkyl or halogen, and X2, X3 and X4, independently, are hydrogen, lower alkyl, lower alkoxy or halogen, R3 is hydrogen, lower alkyl or aryl, R4 is hydrogen, lower alkyl, aryl, aryl-lower alkyl or acyl, R5 is hydrogen or lower alkyl, R6 is hydrogen, lower alkyl, cycloalkyl, Het-lower alkyl or aryl, Het is a monocyclic 6-membered heteroaromatic radical containing one or two nitrogen atoms, which radical may be substituted by lower alkyl, halogen or aryl, and the asterisk denotes the point of attachment, and when R5 and R6 are different, their enantiomers and racemic mixtures thereof, when R1 and R2 are different, their geometric isomers, and pharmaceutically acceptable acid addition salts thereof.
-
(2008/06/13)