The Experts below are selected from a list of 135 Experts worldwide ranked by ideXlab platform

Tadashi Shirasaka - One of the best experts on this subject based on the ideXlab platform.

  • Process Safety Evaluation and Scale-up of a Lactam Reduction with NaBH4 and TFA
    Organic Process Research & Development, 2015
    Co-Authors: Takashi Naka, Hiroki Ozawa, Ken-ichi Toyama, Tadashi Shirasaka
    Abstract:

    The development of a practical and scalable method for the synthesis of Morpholine Derivative 2 via reduction of lactam 1 using NaBH4 and trifluoroacetic acid (TFA) is described. Through the mechanistic studies using 11B NMR spectroscopy, we observed that active species were generated during TFA addition, which avoids the deactivation of the active species involved in the reduction process. Process safety assessments were performed on the basis of the reaction mechanism using reaction calorimetry and gas evolution analyses. Furthermore, safety equipment was prepared to prevent the leakage of diborane gas during the reaction, and the process was successfully scaled up to the pilot plant at a 35 kg scale.

  • Process Safety Evaluation and Scale-up of a Lactam Reduction with NaBH4 and TFA
    2015
    Co-Authors: Takashi Naka, Hiroki Ozawa, Ken-ichi Toyama, Tadashi Shirasaka
    Abstract:

    The development of a practical and scalable method for the synthesis of Morpholine Derivative 2 via reduction of lactam 1 using NaBH4 and trifluoroacetic acid (TFA) is described. Through the mechanistic studies using 11B NMR spectroscopy, we observed that active species were generated during TFA addition, which avoids the deactivation of the active species involved in the reduction process. Process safety assessments were performed on the basis of the reaction mechanism using reaction calorimetry and gas evolution analyses. Furthermore, safety equipment was prepared to prevent the leakage of diborane gas during the reaction, and the process was successfully scaled up to the pilot plant at a 35 kg scale

Takashi Naka - One of the best experts on this subject based on the ideXlab platform.

  • Process Safety Evaluation and Scale-up of a Lactam Reduction with NaBH4 and TFA
    Organic Process Research & Development, 2015
    Co-Authors: Takashi Naka, Hiroki Ozawa, Ken-ichi Toyama, Tadashi Shirasaka
    Abstract:

    The development of a practical and scalable method for the synthesis of Morpholine Derivative 2 via reduction of lactam 1 using NaBH4 and trifluoroacetic acid (TFA) is described. Through the mechanistic studies using 11B NMR spectroscopy, we observed that active species were generated during TFA addition, which avoids the deactivation of the active species involved in the reduction process. Process safety assessments were performed on the basis of the reaction mechanism using reaction calorimetry and gas evolution analyses. Furthermore, safety equipment was prepared to prevent the leakage of diborane gas during the reaction, and the process was successfully scaled up to the pilot plant at a 35 kg scale.

  • Process Safety Evaluation and Scale-up of a Lactam Reduction with NaBH4 and TFA
    2015
    Co-Authors: Takashi Naka, Hiroki Ozawa, Ken-ichi Toyama, Tadashi Shirasaka
    Abstract:

    The development of a practical and scalable method for the synthesis of Morpholine Derivative 2 via reduction of lactam 1 using NaBH4 and trifluoroacetic acid (TFA) is described. Through the mechanistic studies using 11B NMR spectroscopy, we observed that active species were generated during TFA addition, which avoids the deactivation of the active species involved in the reduction process. Process safety assessments were performed on the basis of the reaction mechanism using reaction calorimetry and gas evolution analyses. Furthermore, safety equipment was prepared to prevent the leakage of diborane gas during the reaction, and the process was successfully scaled up to the pilot plant at a 35 kg scale

Ken-ichi Toyama - One of the best experts on this subject based on the ideXlab platform.

  • Process Safety Evaluation and Scale-up of a Lactam Reduction with NaBH4 and TFA
    Organic Process Research & Development, 2015
    Co-Authors: Takashi Naka, Hiroki Ozawa, Ken-ichi Toyama, Tadashi Shirasaka
    Abstract:

    The development of a practical and scalable method for the synthesis of Morpholine Derivative 2 via reduction of lactam 1 using NaBH4 and trifluoroacetic acid (TFA) is described. Through the mechanistic studies using 11B NMR spectroscopy, we observed that active species were generated during TFA addition, which avoids the deactivation of the active species involved in the reduction process. Process safety assessments were performed on the basis of the reaction mechanism using reaction calorimetry and gas evolution analyses. Furthermore, safety equipment was prepared to prevent the leakage of diborane gas during the reaction, and the process was successfully scaled up to the pilot plant at a 35 kg scale.

  • Process Safety Evaluation and Scale-up of a Lactam Reduction with NaBH4 and TFA
    2015
    Co-Authors: Takashi Naka, Hiroki Ozawa, Ken-ichi Toyama, Tadashi Shirasaka
    Abstract:

    The development of a practical and scalable method for the synthesis of Morpholine Derivative 2 via reduction of lactam 1 using NaBH4 and trifluoroacetic acid (TFA) is described. Through the mechanistic studies using 11B NMR spectroscopy, we observed that active species were generated during TFA addition, which avoids the deactivation of the active species involved in the reduction process. Process safety assessments were performed on the basis of the reaction mechanism using reaction calorimetry and gas evolution analyses. Furthermore, safety equipment was prepared to prevent the leakage of diborane gas during the reaction, and the process was successfully scaled up to the pilot plant at a 35 kg scale

Hiroki Ozawa - One of the best experts on this subject based on the ideXlab platform.

  • Process Safety Evaluation and Scale-up of a Lactam Reduction with NaBH4 and TFA
    Organic Process Research & Development, 2015
    Co-Authors: Takashi Naka, Hiroki Ozawa, Ken-ichi Toyama, Tadashi Shirasaka
    Abstract:

    The development of a practical and scalable method for the synthesis of Morpholine Derivative 2 via reduction of lactam 1 using NaBH4 and trifluoroacetic acid (TFA) is described. Through the mechanistic studies using 11B NMR spectroscopy, we observed that active species were generated during TFA addition, which avoids the deactivation of the active species involved in the reduction process. Process safety assessments were performed on the basis of the reaction mechanism using reaction calorimetry and gas evolution analyses. Furthermore, safety equipment was prepared to prevent the leakage of diborane gas during the reaction, and the process was successfully scaled up to the pilot plant at a 35 kg scale.

  • Process Safety Evaluation and Scale-up of a Lactam Reduction with NaBH4 and TFA
    2015
    Co-Authors: Takashi Naka, Hiroki Ozawa, Ken-ichi Toyama, Tadashi Shirasaka
    Abstract:

    The development of a practical and scalable method for the synthesis of Morpholine Derivative 2 via reduction of lactam 1 using NaBH4 and trifluoroacetic acid (TFA) is described. Through the mechanistic studies using 11B NMR spectroscopy, we observed that active species were generated during TFA addition, which avoids the deactivation of the active species involved in the reduction process. Process safety assessments were performed on the basis of the reaction mechanism using reaction calorimetry and gas evolution analyses. Furthermore, safety equipment was prepared to prevent the leakage of diborane gas during the reaction, and the process was successfully scaled up to the pilot plant at a 35 kg scale

Jean-marie Pagès - One of the best experts on this subject based on the ideXlab platform.

  • molecules 5-Arylideneimidazolones with Amine at Position 3 as Potential Antibiotic Adjuvants against Multidrug Resistant Bacteria
    Molecules, 2019
    Co-Authors: Ewa Żesławska, Aneta Kaczor, Karolina Witek, Sabina Podlewska, Joanna Czekajewska, Annamaria Lubelska, Wojciech Nitek, Gniewomir Latacz, Sandrine Alibert, Jean-marie Pagès
    Abstract:

    Searching for new chemosensitizers of bacterial multidrug resistance (MDR), chemical modifications of (Z)-5-(4-chlorobenzylidene)-2-(4-methylpiperazin-1-yl)-3H-imidazol-4(5H)-one (6) were performed. New compounds (7-17), with fused aromatic rings at position 5, were designed and synthesized. Crystallographic X-ray analysis proved that the final compounds (7-17) were substituted with tertiary amine-propyl moiety at position 3 and primary amine group at 2 due to intramolecular Dimroth rearrangement. New compounds were evaluated on their antibiotic adjuvant properties in either Gram-positive or Gram-negative bacteria. Efflux pump inhibitor (EPI) properties towards the AcrAB-TolC pump in Enterobacter aerogenes (EA289) were investigated in the real-time efflux (RTE) assay. Docking and molecular dynamics were applied to estimate an interaction of compounds 6-17 with penicillin binding protein (PBP2a). In vitro ADME-Tox properties were evaluated for compound 9. Most of the tested compounds reduced significantly (4-32-fold) oxacillin MIC in highly resistant MRSA HEMSA 5 strain. The anthracene-Morpholine Derivative (16) was the most potent (32-fold reduction). The tested compounds displayed significant EPI properties during RTE assay (37-97%). The naphthyl-methylpiperazine Derivative 9 showed the most potent "dual action" of both oxacillin adjuvant (MRSA) and EPI (E. aerogenes). Molecular modeling results suggested the allosteric mechanism of action of the imidazolones, which improved binding of oxacillin in the PBP2a active site in MRSA.

  • 5-Arylideneimidazolones with Amine at Position 3 as Potential Antibiotic Adjuvants against Multidrug Resistant Bacteria
    MDPI AG, 2019
    Co-Authors: Aneta Kaczor, Ewa Żesławska, Karolina Witek, Sabina Podlewska, Joanna Czekajewska, Annamaria Lubelska, Wojciech Nitek, Gniewomir Latacz, Sandrine Alibert, Jean-marie Pagès
    Abstract:

    Searching for new chemosensitizers of bacterial multidrug resistance (MDR), chemical modifications of (Z)-5-(4-chlorobenzylidene)-2-(4-methylpiperazin-1-yl)-3H-imidazol-4(5H)-one (6) were performed. New compounds (7⁻17), with fused aromatic rings at position 5, were designed and synthesized. Crystallographic X-ray analysis proved that the final compounds (7⁻17) were substituted with tertiary amine-propyl moiety at position 3 and primary amine group at 2 due to intramolecular Dimroth rearrangement. New compounds were evaluated on their antibiotic adjuvant properties in either Gram-positive or Gram-negative bacteria. Efflux pump inhibitor (EPI) properties towards the AcrAB-TolC pump in Enterobacter aerogenes (EA289) were investigated in the real-time efflux (RTE) assay. Docking and molecular dynamics were applied to estimate an interaction of compounds 6⁻17 with penicillin binding protein (PBP2a). In vitro ADME-Tox properties were evaluated for compound 9. Most of the tested compounds reduced significantly (4-32-fold) oxacillin MIC in highly resistant MRSA HEMSA 5 strain. The anthracene-Morpholine Derivative (16) was the most potent (32-fold reduction). The tested compounds displayed significant EPI properties during RTE assay (37⁻97%). The naphthyl-methylpiperazine Derivative 9 showed the most potent “dual action„ of both oxacillin adjuvant (MRSA) and EPI (E. aerogenes). Molecular modeling results suggested the allosteric mechanism of action of the imidazolones, which improved binding of oxacillin in the PBP2a active site in MRSA