- Fast and efficient tritium labelling of the nonsteroidal anti-inflammatory drugs naproxen, tolmetin, and zomepirac
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Fast and efficient tritium labelling of the nonsteroidal anti-inflammatory drugs naproxen, tolmetin and zomepirac is reported. Naproxen along with its (R)-enantiomer were labelled by catalytic tritium-halogen exchange of the corresponding 5-bromo derivatives providing [3H]naproxen with a specific activity of 25.4 Ci/mmol. Tolmetin and zomepirac were labelled by the hydrogen isotope exchange reaction using Crabtree's catalyst. This provided [3H]tolmetin and [3H]zomepirac with specific activities of 80.8 and 64.3 Ci/mmol, respectively. All compounds were obtained in high radiochemical purity (>98%). Copyright
- Johansen, Steen K.,Sorensen, Lone,Martiny, Lars
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- Construction of Axially Chiral Arylborons via Atroposelective Miyaura Borylation
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Compared with the well-developed centrally chiral boron chemistry, C-B axially chiral chemistry remains elusive and challenging. Herein we report the first atroposelective Miyaura borylation of bromoarenes with unsymmetrical diboron reagents for the direct catalytic synthesis of optically active atropisomeric arylborons. This reaction features broad substrate scope and produces axially chiral arylborons with high yields and good enantioselectivities.
- He, Yong,Li, Wangyang,Mao, Yanfei,Song, Qiuling,Wang, Hao,Xu, Jie,Yang, Kai
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supporting information
p. 10048 - 10053
(2021/07/21)
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- Practical, mild and efficient electrophilic bromination of phenols by a new I(iii)-based reagent: The PIDA-AlBr3 system
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A practical electrophilic bromination procedure for phenols and phenol-ethers was developed under efficient and very mild reaction conditions. A broad scope of arenes was investigated, including the benzimidazole and carbazole core as well as analgesics such as naproxen and paracetamol. The new I(iii)-based brominating reagent PhIOAcBr is operationally easy to prepare by mixing PIDA and AlBr3. Our DFT calculations suggest that this is likely the brominating active species, which is prepared in situ or isolated after centrifugation. Its stability at 4 °C after preparation was confirmed over a period of one month and no significant loss of its reactivity was observed. Additionally, the gram-scale bromination of 2-naphthol proceeds with excellent yields. Even for sterically hindered substrates, a moderately good reactivity is observed.
- Satkar, Yuvraj,Ramadoss, Velayudham,Nahide, Pradip D.,García-Medina, Ernesto,Juárez-Ornelas, Kevin A.,Alonso-Castro, Angel J.,Chávez-Rivera, Ruben,Jiménez-Halla, J. Oscar C.,Solorio-Alvarado, César R.
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p. 17806 - 17812
(2018/05/28)
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- Trichosporon beigelli esterase (TBE): A versatile esterase for the resolution of economically important racemates
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A hydrolase producing strain Trichosporon beigelli esterase (TBE) isolated from local cottage cheese in its native form has displayed versatility and high efficacy in the kinetic resolution of a wide range of economically important substrates, which include racemic secondary alcohols, such as 1-(6-methoxy-2-naphthyl)ethanol (E ～ 316), 1-(3,4-methylenedioxyphenyl) ethanol and pentanol (E ～ 180 and 156 resp.), and alkyl esters of carboxylic acids such as ibuprofen (E ～ 340), 2-(benzylthio)propanoic acid (E ～ 1000). In other substrates such as in the primary alcohol 2-(6-methoxy-2- naphthyl)propan-1-ol and carboxylic acids such as 2-(5-bromo-6-methoxy-2- naphthyl)propanoic acid, 2-(2-naphthyloxy)propanoic acid, and substituted 2-thiopropanoic acids, it displayed moderate to low selectivity. Commercial lipases such as CCL, PPL, and PSL were also used in the resolution of the substrates for comparative studies.
- Koul, Surrinder,Koul, Jawahir Lal,Singh, Budh,Kapoor, Munish,Parshad, Rajinder,Manhas, Kuldeep S.,Taneja, Subhash C.,Qazi, Ghulam N.
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p. 2575 - 2591
(2007/10/03)
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- Stereo-selective synthesis of 2-aryl-propionic acids of high optical purity by using chiral oxazolines
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The present invention relates to a stereospecific chemical synthesis of optically pure enantiomers of 2-aryl-alkanoic acids, especially those of the biologically active (S)-aryl-propionic acids, in good chemical yields, useful for preparing large quantities thereof, and having a high optical purity.
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- Carboxylic acid synthesis process
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A process is described for preparing alpha-arylalkanoic acids, which comprises preparing and subsequently rearranging ketals of formula STR1 (in which Ar, R, R1, R2 and R4 have the meanings given in the description). The ketals of formula II are prepared from the corresponding alpha-hydroxyketals. The rearrangement reaction is conducted under mild conditions.
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- A STEREOCONVERGENT STRATEGY FOR THE SYNTHESIS OF ENANTIOMERICALLY PURE (R)-(-) AND (S)-(+)-2-(6-METHOXY-2-NAPHTHYL)-PROPANOIC ACID (NAPROXEN)
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A synthetic strategy for resolving diastereoselective imperfections associated with using a chiral auxillary has been designed.The impact of this imperfection is a lower enantiomeric purity of the final product.A solution for the synthesis of Naproxen 1, an important antiinflammatory drug, using tartaric acid as chiral auxillary, derives from an equivalent of a kinetic resolution.Using the differential rate of a rearrangement versus an intramolecular carboxylate alkylation, enantiomerically pure Naproxen 1 can be obtained from diastereomeric mixtures of bromo acetals diacids 9a, b enriched in 9a.Furthermore, the product coming from the intramolecular carboxylate alkylation of the minor diastereomer 9b is also converted into Naproxen 1.This stereoconvergence permits complete productive utilization of the diastereomeric mixture 9a, b.
- Giordano, Claudio,Castaldi, Graziano,Cavicchioli, Silvia,Villa, Marco
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p. 4243 - 4252
(2007/10/02)
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- Process for the preparation of optically active alpha-acrylalkanoic acids and novel intermediates thereof
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A new enantioselective process is described for preparing optically active alpha-arylalkanoic acids by: (a) halogenation on the aliphatic carbon atom alpha to the ketal group, of ketals of formula STR1 in which Ar represents an aryl, optionally substituted; R represents a C1 -C4 alkyl; R1 and R2, represents a hydroxy, a O- M+, OR3 or NR4 R5 group; the carbon atoms indicated by an asterisk both simultaneously are in (R) or (S) configuration. This reaction is diastereoselective, so that a mixture of alpha-haloketals is obtained in which one of the two epimers prevails, and generally strongly prevails, over the other. (b) rearrangement of the haloketals of formula STR2 in which X is Cl, Br or I to alpha-arylalkanoic acids in a single stage or in two successive stages, by way of esters of formula STR3 The compounds (A) and (C) are all new compounds. The rearrangement step (b) may be performed under new, inventive conditions. The esters of formula (C) have pharmacological activity analogous to that of the corresponding alpha-arylalkanoic acids.
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- Carboxylic acid synthesis process
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A process is described for preparing alpha-arylalkanoic acids, which comprises preparing and subsequently rearranging ketals of formula (in which Ar, R, R1, R2 and R4 have the meanings given in the description). The ketals of formula II are prepared from the corresponding alpha-hydroxyketals. The rearrangement reaction is conducted under mild conditions.
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- Tartaric Acid, an Efficient Chiral Auxiliary: New Asymmetric Synthesis of 2-Alkyl-2-arylacetic Acids
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A highly enantioselective synthesis of 2-alkyl-2-arylacetic acids, an important class of antiinflammatory agents, based on a new diastereoselective α-bromination of homochiral acetals 1 and on the stereospecific silver-promoted rearrangement of the corresponding homochiral α-bromo acetals 2 and 3, is reported.The new methodology represents a meaningful example of the use of tartaric acid as efficient and economic chiral auxiliary.The asymmetric bromination of 1 is of general character and occurs with very high diastereoselectivity, even at room temperature; a mechanism for the new reaction is proposed.The overall process has been successfully applied to the preparation of enantiomerically pure 2-alkyl-2-arylacetic acids, among them (2S)-(+)-2-(6-methoxy-2-naphthyl)propanoic acid (Naproxen)
- Castaldi, Graziano,Cavicchioli, Silvia,Giordano, Claudio,Uggeri, Fulvio
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p. 3018 - 3027
(2007/10/02)
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- Process for the preparation of optically active alpha-arylalkanoic acids and novel intermediates thereof
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A new enantioselective process is described for preparing optically active alpha-arylalkanoic acids by: (a) halogenation on the aliphatic carbon atom alpha to the ketal group, of ketals of formula STR1 in which Ar represents an aryl, optionally substituted; R represents a C1 -C4 alkyl; R1 and R2, represents a hydroxy, a O- M+, OR3 or NR4 R5 group; the carbon atoms indicated by an asterisk both simultaneously are in (R) or (S) configuration. This reaction is diastereoselective, so that a misture of alpha-haloketals is obtained in which one of the two epimers prevails, and generally strongly prevails, over the other. (b) rearrangement of the haloketals of formula STR2 in which X is Cl, Br or I to alpha-arylalkanoic acids in a single stage or in two successive stages, by way of esters of formula STR3 The compounds (A) and (C) are all new compounds. The rearrangement step (b) may be performed under new, inventive conditions. The esters of formula (C) have pharmacological activity analogous to that of the corresponding alpha-arylalkanoic acids.
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