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C. Oliver Kappe - One of the best experts on this subject based on the ideXlab platform.
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Design and Optimization of a Continuous Stirred Tank Reactor Cascade for Membrane-Based Diazomethane Production: Synthesis of α-Chloroketones
Organic Process Research & Development, 2019Co-Authors: Michaela Wernik, Peter Poechlauer, Christoph Schmoelzer, Doris Dallinger, C. Oliver KappeAbstract:The development of a continuous diazomethane generator comprising a continuous stirred tank reactor (CSTR) cascade and membrane separation technology is reported. This reactor concept was applied for the telescoped three-step synthesis of a chiral α-Chloroketone, a key building block for many HIV protease inhibitors, via a modified Arndt–Eistert reaction starting from N-protected l-phenylalanine. The initial mixed anhydride was generated in a coil reactor and directly introduced into the CSTR diazomethane cascade. The use of a semipermeable Teflon membrane (AF-2400) allowed the generation of anhydrous diazomethane, which diffuses through the membrane into the CSTR where it is immediately consumed by the anhydride to furnish the corresponding diazoketone. The subsequent halogenation with concentrated HCl was performed downstream in batch and allowed production of the α-Chloroketone on a multigram scale, with a productivity of 1.54 g/h (5.2 mmol/h).
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One-Pot Synthesis of α-Haloketones Employing a Membrane-Based Semibatch Diazomethane Generator
Journal of Flow Chemistry, 2016Co-Authors: Silvia Garbarino, Javier Guerra, Peter Poechlauer, Bernhard Gutmann, C. Oliver KappeAbstract:The crucial structural motive in viral protease inhibitors such as atazanavir and darunavir is a chiral aminoalcohol structure. The structure is generally introduced during the synthesis of the protease inhibitorvia an α-Chloroketone intermediate. The α-Chloroketone can be synthesized in a multistep sequence from naturally occurring L -phenylalanine. Herein, we report a one- pot synthesis of an α-Chloroketone starting from N -Boc- L -phenylalanine in a novel type of “tube-in-flask” semi-batch diazomethane generator. Activation of the amino acid to the mixed anhydride was carried out in the flask, while diazomethanewas generated from insituformed N -nitroso- N -methylurea within a gas-permeable tubing contained inside theflask. The diazomethane diffused through the gas-selective membrane into the flask, and reacted with the anhydride to the diazoketone (Arndt-Eistert reaction). The addition of aqueous hydrogen chloride provided the α-Chloroketone and destroyed any excess of diazomethane. The desired product was isolated by extraction in excellent purity and yield (90%–96%).
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Chiral Chlorohydrins from the Biocatalyzed Reduction of Chloroketones: Chiral Building Blocks for Antiretroviral Drugs
Chemcatchem, 2015Co-Authors: Amanda S. De Miranda, Robert C. Simon, Barbara Grischek, Gabriel C. De Paula, Bruno A. C. Horta, Leandro S. M. De Miranda, Wolfgang Kroutil, C. Oliver Kappe, Rodrigo O. M. A. De SouzaAbstract:E. coli cells that contain overexpressed alcohol dehydrogenases (ADHs) were screened as biocatalysts for the stereoselective reduction of Chloroketones 5 a–d, the corresponding halohydrins 6 a–d of which are building blocks in the synthesis of antiretroviral drugs. Among them, ADH from Sphingobium yanoikuyae was found to reduce Chloroketone 5 c with a high stereoselectivity (90 % de) and conversion (85 %) to furnish threo halohydrin (R,S)-6 c. ADH from Ralstonia sp. (RasADH) was able to reduce 5 a and 5 b with complementary diastereoselectivity to provide access to both threo and erythro halohydrins through “substrate-based” stereocontrol. The RasADH-catalyzed reductions were optimized to provide (R,S)-6 a with 98 % conversion and 84 % diastereomeric excess (de) and (S,S)-6 b with 95 % conversion and 86 % de. Molecular modeling studies showed that 5 b, which features a carboxybenzyl protecting group, is able to bind to the enzyme catalytic site in an “inverted” mode in comparison to tert-butyloxycarbonyl- and methyloxycarbonyl-protected substrates 5 a and 5 c, which sheds light on the observed switching of the stereopreference. RasADH-catalyzed reductions were optimized to provide (R,S)-6 a with 98 % conversion and 84 % de and (S,S)-6 b with 95 % conversion and 86 % de.
Ramesh N Patel - One of the best experts on this subject based on the ideXlab platform.
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microbial reduction of alpha Chloroketone to alpha chlorohydrin
Journal of Industrial Microbiology & Biotechnology, 2001Co-Authors: Animesh Goswami, K D Mirfakhrae, Michael J Totleben, Shankar Swaminathan, Ramesh N PatelAbstract:: Microbial reduction of alpha-Chloroketone to alpha-chlorohydrin was studied as one of the approaches for construction of the chiral center of the corresponding epoxide. About 100 microorganisms covering many species of Candida, Pichia, Hansenula, Geotrichum, Rhodococcus and Aureobasidium were screened to reduce the alpha-Chloroketone stereospecifically. Many strains provided the R-alpha-chlorohydrin with 100% enantiomeric excess (ee), e.g., Candida sonorensis SC 16117, Geotrichum candidum SC 5469, Rhodotorula glutinis SC 16293, Sphingomonas paucimobilis SC 16113, Pichia silvicola SC 16159 and Rhodococcus equi SC 15835. Few microorganisms showed preferential formation of S-alpha-chlorohydrin after reduction. Among them, Pichia pinus SC 13864 and two Pichia methanolica strains SC 16116 and SC 13860 were the best, providing the S-alpha-chlorohydrin with ee of 88%, 79% and 78%, respectively. The enantiospecificity of the reduction by these Pichia species can be modified by changing the pH or prior heat treatment of the cells and S-alpha-chlorohydrin with > or =95% ee was obtained by appropriate modification of reaction conditions.
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Microbial reduction of ?-Chloroketone to ?-chlorohydrin
Journal of Industrial Microbiology & Biotechnology, 2001Co-Authors: Animesh Goswami, K D Mirfakhrae, Michael J Totleben, Shankar Swaminathan, Ramesh N PatelAbstract:: Microbial reduction of alpha-Chloroketone to alpha-chlorohydrin was studied as one of the approaches for construction of the chiral center of the corresponding epoxide. About 100 microorganisms covering many species of Candida, Pichia, Hansenula, Geotrichum, Rhodococcus and Aureobasidium were screened to reduce the alpha-Chloroketone stereospecifically. Many strains provided the R-alpha-chlorohydrin with 100% enantiomeric excess (ee), e.g., Candida sonorensis SC 16117, Geotrichum candidum SC 5469, Rhodotorula glutinis SC 16293, Sphingomonas paucimobilis SC 16113, Pichia silvicola SC 16159 and Rhodococcus equi SC 15835. Few microorganisms showed preferential formation of S-alpha-chlorohydrin after reduction. Among them, Pichia pinus SC 13864 and two Pichia methanolica strains SC 16116 and SC 13860 were the best, providing the S-alpha-chlorohydrin with ee of 88%, 79% and 78%, respectively. The enantiospecificity of the reduction by these Pichia species can be modified by changing the pH or prior heat treatment of the cells and S-alpha-chlorohydrin with > or =95% ee was obtained by appropriate modification of reaction conditions.
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Microbial reduction of α-Chloroketone to α-chlorohydrin
Journal of Industrial Microbiology and Biotechnology, 2001Co-Authors: Animesh Goswami, K D Mirfakhrae, Michael J Totleben, Shankar Swaminathan, Ramesh N PatelAbstract:Microbial reduction of α-Chloroketone to α-chlorohydrin was studied as one of the approaches for construction of the chiral center of the corresponding epoxide. About 100 microorganisms covering many species of Candida , Pichia , Hansenula , Geotrichum , Rhodococcus and Aureobasidium were screened to reduce the α-Chloroketone stereospecifically. Many strains provided the R -α-chlorohydrin with 100% enantiomeric excess (ee), e.g., Candida sonorensis SC 16117, Geotrichum candidum SC 5469, Rhodotorula glutinis SC 16293, Sphingomonas paucimobilis SC 16113, Pichia silvicola SC 16159 and Rhodococcus equi SC 15835. Few microorganisms showed preferential formation of S -α-chlorohydrin after reduction. Among them, Pichia pinus SC 13864 and two Pichia methanolica strains SC 16116 and SC 13860 were the best, providing the S -α-chlorohydrin with ee of 88%, 79% and 78%, respectively. The enantiospecificity of the reduction by these Pichia species can be modified by changing the pH or prior heat treatment of the cells and S -α-chlorohydrin with ≥95% ee was obtained by appropriate modification of reaction conditions. Journal of Industrial Microbiology & Biotechnology (2001) 26, 259–262.
Ahmad Khabbazi Habibi - One of the best experts on this subject based on the ideXlab platform.
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Reaction of tert-Butyl Isocyanide with Alkyl Propiolates in the Presence of α-Chloroketones.
ChemInform, 2013Co-Authors: Sakineh Asghari, Zhila Tayebi, Ahmad Khabbazi HabibiAbstract:This simple entry to the one-pot synthesis of chlorinated γ-iminolactone derivatives provides following advantages: i) simultaneous formation of several bonds in one step; ii) simple and easily available starting materials; iii) neutral conditions.
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Reaction of tert-Butyl Isocyanide with Alkyl Propiolates in the Presence of α-Chloroketones
Journal of Heterocyclic Chemistry, 2013Co-Authors: Sakineh Asghari, Zhila Tayebi, Ahmad Khabbazi HabibiAbstract:tert-Butyl isocyanide reacts with α-Chloroketones in the presence of alkyl propiolates in one pot to afford functionalized γ-iminolactones as sole product in good yields.
K D Mirfakhrae - One of the best experts on this subject based on the ideXlab platform.
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Microbial reduction of α-Chloroketone to α-chlorohydrin
Journal of Industrial Microbiology and Biotechnology, 2002Co-Authors: A Goswami, K D Mirfakhrae, M J Totleben, S Swaminathan, R N PatelAbstract:(2001) 26, 259–262 DOI: 10.1038/sj/jim/7000080
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microbial reduction of alpha Chloroketone to alpha chlorohydrin
Journal of Industrial Microbiology & Biotechnology, 2001Co-Authors: Animesh Goswami, K D Mirfakhrae, Michael J Totleben, Shankar Swaminathan, Ramesh N PatelAbstract:: Microbial reduction of alpha-Chloroketone to alpha-chlorohydrin was studied as one of the approaches for construction of the chiral center of the corresponding epoxide. About 100 microorganisms covering many species of Candida, Pichia, Hansenula, Geotrichum, Rhodococcus and Aureobasidium were screened to reduce the alpha-Chloroketone stereospecifically. Many strains provided the R-alpha-chlorohydrin with 100% enantiomeric excess (ee), e.g., Candida sonorensis SC 16117, Geotrichum candidum SC 5469, Rhodotorula glutinis SC 16293, Sphingomonas paucimobilis SC 16113, Pichia silvicola SC 16159 and Rhodococcus equi SC 15835. Few microorganisms showed preferential formation of S-alpha-chlorohydrin after reduction. Among them, Pichia pinus SC 13864 and two Pichia methanolica strains SC 16116 and SC 13860 were the best, providing the S-alpha-chlorohydrin with ee of 88%, 79% and 78%, respectively. The enantiospecificity of the reduction by these Pichia species can be modified by changing the pH or prior heat treatment of the cells and S-alpha-chlorohydrin with > or =95% ee was obtained by appropriate modification of reaction conditions.
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Microbial reduction of ?-Chloroketone to ?-chlorohydrin
Journal of Industrial Microbiology & Biotechnology, 2001Co-Authors: Animesh Goswami, K D Mirfakhrae, Michael J Totleben, Shankar Swaminathan, Ramesh N PatelAbstract:: Microbial reduction of alpha-Chloroketone to alpha-chlorohydrin was studied as one of the approaches for construction of the chiral center of the corresponding epoxide. About 100 microorganisms covering many species of Candida, Pichia, Hansenula, Geotrichum, Rhodococcus and Aureobasidium were screened to reduce the alpha-Chloroketone stereospecifically. Many strains provided the R-alpha-chlorohydrin with 100% enantiomeric excess (ee), e.g., Candida sonorensis SC 16117, Geotrichum candidum SC 5469, Rhodotorula glutinis SC 16293, Sphingomonas paucimobilis SC 16113, Pichia silvicola SC 16159 and Rhodococcus equi SC 15835. Few microorganisms showed preferential formation of S-alpha-chlorohydrin after reduction. Among them, Pichia pinus SC 13864 and two Pichia methanolica strains SC 16116 and SC 13860 were the best, providing the S-alpha-chlorohydrin with ee of 88%, 79% and 78%, respectively. The enantiospecificity of the reduction by these Pichia species can be modified by changing the pH or prior heat treatment of the cells and S-alpha-chlorohydrin with > or =95% ee was obtained by appropriate modification of reaction conditions.
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Microbial reduction of α-Chloroketone to α-chlorohydrin
Journal of Industrial Microbiology and Biotechnology, 2001Co-Authors: Animesh Goswami, K D Mirfakhrae, Michael J Totleben, Shankar Swaminathan, Ramesh N PatelAbstract:Microbial reduction of α-Chloroketone to α-chlorohydrin was studied as one of the approaches for construction of the chiral center of the corresponding epoxide. About 100 microorganisms covering many species of Candida , Pichia , Hansenula , Geotrichum , Rhodococcus and Aureobasidium were screened to reduce the α-Chloroketone stereospecifically. Many strains provided the R -α-chlorohydrin with 100% enantiomeric excess (ee), e.g., Candida sonorensis SC 16117, Geotrichum candidum SC 5469, Rhodotorula glutinis SC 16293, Sphingomonas paucimobilis SC 16113, Pichia silvicola SC 16159 and Rhodococcus equi SC 15835. Few microorganisms showed preferential formation of S -α-chlorohydrin after reduction. Among them, Pichia pinus SC 13864 and two Pichia methanolica strains SC 16116 and SC 13860 were the best, providing the S -α-chlorohydrin with ee of 88%, 79% and 78%, respectively. The enantiospecificity of the reduction by these Pichia species can be modified by changing the pH or prior heat treatment of the cells and S -α-chlorohydrin with ≥95% ee was obtained by appropriate modification of reaction conditions. Journal of Industrial Microbiology & Biotechnology (2001) 26, 259–262.
Animesh Goswami - One of the best experts on this subject based on the ideXlab platform.
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microbial reduction of alpha Chloroketone to alpha chlorohydrin
Journal of Industrial Microbiology & Biotechnology, 2001Co-Authors: Animesh Goswami, K D Mirfakhrae, Michael J Totleben, Shankar Swaminathan, Ramesh N PatelAbstract:: Microbial reduction of alpha-Chloroketone to alpha-chlorohydrin was studied as one of the approaches for construction of the chiral center of the corresponding epoxide. About 100 microorganisms covering many species of Candida, Pichia, Hansenula, Geotrichum, Rhodococcus and Aureobasidium were screened to reduce the alpha-Chloroketone stereospecifically. Many strains provided the R-alpha-chlorohydrin with 100% enantiomeric excess (ee), e.g., Candida sonorensis SC 16117, Geotrichum candidum SC 5469, Rhodotorula glutinis SC 16293, Sphingomonas paucimobilis SC 16113, Pichia silvicola SC 16159 and Rhodococcus equi SC 15835. Few microorganisms showed preferential formation of S-alpha-chlorohydrin after reduction. Among them, Pichia pinus SC 13864 and two Pichia methanolica strains SC 16116 and SC 13860 were the best, providing the S-alpha-chlorohydrin with ee of 88%, 79% and 78%, respectively. The enantiospecificity of the reduction by these Pichia species can be modified by changing the pH or prior heat treatment of the cells and S-alpha-chlorohydrin with > or =95% ee was obtained by appropriate modification of reaction conditions.
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Microbial reduction of ?-Chloroketone to ?-chlorohydrin
Journal of Industrial Microbiology & Biotechnology, 2001Co-Authors: Animesh Goswami, K D Mirfakhrae, Michael J Totleben, Shankar Swaminathan, Ramesh N PatelAbstract:: Microbial reduction of alpha-Chloroketone to alpha-chlorohydrin was studied as one of the approaches for construction of the chiral center of the corresponding epoxide. About 100 microorganisms covering many species of Candida, Pichia, Hansenula, Geotrichum, Rhodococcus and Aureobasidium were screened to reduce the alpha-Chloroketone stereospecifically. Many strains provided the R-alpha-chlorohydrin with 100% enantiomeric excess (ee), e.g., Candida sonorensis SC 16117, Geotrichum candidum SC 5469, Rhodotorula glutinis SC 16293, Sphingomonas paucimobilis SC 16113, Pichia silvicola SC 16159 and Rhodococcus equi SC 15835. Few microorganisms showed preferential formation of S-alpha-chlorohydrin after reduction. Among them, Pichia pinus SC 13864 and two Pichia methanolica strains SC 16116 and SC 13860 were the best, providing the S-alpha-chlorohydrin with ee of 88%, 79% and 78%, respectively. The enantiospecificity of the reduction by these Pichia species can be modified by changing the pH or prior heat treatment of the cells and S-alpha-chlorohydrin with > or =95% ee was obtained by appropriate modification of reaction conditions.
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Microbial reduction of α-Chloroketone to α-chlorohydrin
Journal of Industrial Microbiology and Biotechnology, 2001Co-Authors: Animesh Goswami, K D Mirfakhrae, Michael J Totleben, Shankar Swaminathan, Ramesh N PatelAbstract:Microbial reduction of α-Chloroketone to α-chlorohydrin was studied as one of the approaches for construction of the chiral center of the corresponding epoxide. About 100 microorganisms covering many species of Candida , Pichia , Hansenula , Geotrichum , Rhodococcus and Aureobasidium were screened to reduce the α-Chloroketone stereospecifically. Many strains provided the R -α-chlorohydrin with 100% enantiomeric excess (ee), e.g., Candida sonorensis SC 16117, Geotrichum candidum SC 5469, Rhodotorula glutinis SC 16293, Sphingomonas paucimobilis SC 16113, Pichia silvicola SC 16159 and Rhodococcus equi SC 15835. Few microorganisms showed preferential formation of S -α-chlorohydrin after reduction. Among them, Pichia pinus SC 13864 and two Pichia methanolica strains SC 16116 and SC 13860 were the best, providing the S -α-chlorohydrin with ee of 88%, 79% and 78%, respectively. The enantiospecificity of the reduction by these Pichia species can be modified by changing the pH or prior heat treatment of the cells and S -α-chlorohydrin with ≥95% ee was obtained by appropriate modification of reaction conditions. Journal of Industrial Microbiology & Biotechnology (2001) 26, 259–262.