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Your search keyword '"Maloney, Kevin M."' showing total 13 results
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13 results on '"Maloney, Kevin M."'

4. Development of a Biocatalytic Aerobic Oxidation for the Manufacturing Route to Islatravir.

Author

Shaw, Megan H., Fryszkowska, Anna, Alvizo, Oscar, Attadgie, Ilana, Borra-Garske, Margie, Devine, Paul N., Duan, Da, Grosser, Shane T., Forstater, Jacob H., Hughes, Gregory J., Maloney, Kevin M., Margelefsky, Eric L., Mattern, Keith A., Miller, Margaret T., Nawrat, Christopher C., Nazor, Jovana, Orth, Peter, Ouimet, Claire M., Robaire, Sandra A., and Ruccolo, Serge

Published
2024
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5. Use of a Dynamic Flow Platform To Translate a Batch Immobilized Transaminase Process to a Packed Bed Reactor for the Synthesis of an Intermediate of Nemtabrutinib.

Author

Di Maso, Michael J., Kuethe, Jeffrey T., Narsimhan, Karthik, Burris, Matthew, Chung, Cheol K., DiBenedetto, Michael, Forstater, Jacob H., Grosser, Shane T., Kuhl, Nadine, Lévesque, François, Maguire, Anne, Maloney, Kevin M., McMullen, Jonathan P., Prier, Christopher K., Qi, Ji, Rivera, Nelo R., Wang, Zhixun, Wyvratt, Brian M., and Zewge, Daniel

Published
2024
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6. Development of a Biocatalytic Aerobic Oxidation for the Manufacturing Route to Islatravir

Author

Shaw, Megan H., primary, Fryszkowska, Anna, additional, Alvizo, Oscar, additional, Attadgie, Ilana, additional, Borra-Garske, Margie, additional, Devine, Paul N., additional, Duan, Da, additional, Forstater, Jacob H., additional, Grosser, Shane T., additional, Hughes, Gregory J., additional, Maloney, Kevin M., additional, Margelefsky, Eric L., additional, Mattern, Keith A., additional, Miller, Margaret T., additional, Nawrat, Christopher C., additional, Nazor, Jovana, additional, Orth, Peter, additional, Ouimet, Claire M., additional, Robaire, Sandra A., additional, Ruccolo, Serge, additional, Schwalm, Erica L., additional, Verma, Deeptak, additional, Xiao, Li, additional, and Zhang, Victoria, additional

Published
2023
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7. Amination of a Green Solvent via Immobilized Biocatalysis for the Synthesis of Nemtabrutinib

Author

Prier, Christopher K., primary, Camacho Soto, Karla, additional, Forstater, Jacob H., additional, Kuhl, Nadine, additional, Kuethe, Jeffrey T., additional, Cheung-Lee, Wai Ling, additional, Di Maso, Michael J., additional, Eberle, Claire M., additional, Grosser, Shane T., additional, Ho, Hsing-I, additional, Hoyt, Erik, additional, Maguire, Anne, additional, Maloney, Kevin M., additional, Makarewicz, Amanda, additional, McMullen, Jonathan P., additional, Moore, Jeffrey C., additional, Murphy, Grant S., additional, Narsimhan, Karthik, additional, Pan, Weilan, additional, Rivera, Nelo R., additional, Saha-Shah, Anumita, additional, Thaisrivongs, David A., additional, Verma, Deeptak, additional, Wyatt, Adeya, additional, and Zewge, Daniel, additional

Published
2023
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9. Kilo-Scale Electrochemical Oxidation of a Thioether to a Sulfone: A Workflow for Scaling up Electrosynthesis

Author

Bottecchia, Cecilia, primary, Lehnherr, Dan, additional, Lévesque, François, additional, Reibarkh, Mikhail, additional, Ji, Yining, additional, Rodrigues, Vailankanni L., additional, Wang, Heather, additional, Lam, Yu-hong, additional, Vickery, Thomas P., additional, Armstrong, Brittany M., additional, Mattern, Keith A., additional, Stone, Kevin, additional, Wismer, Michael K., additional, Singh, Andrew N., additional, Regalado, Erik L., additional, Maloney, Kevin M., additional, and Strotman, Neil A., additional

Published
2022
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11. Engineered Ribosyl-1-Kinase Enables Concise Synthesis of Molnupiravir, an Antiviral for COVID-19.

Author

McIntosh, John A., Benkovics, Tamas, Silverman, Steven M., Huffman, Mark A., Kong, Jongrock, Maligres, Peter E., Itoh, Tetsuji, Yang, Hao, Verma, Deeptak, Pan, Weilan, Ho, Hsing-I, Vroom, Jonathan, Knight, Anders M., Hurtak, Jessica A., Klapars, Artis, Fryszkowska, Anna, Morris, William J., Strotman, Neil A., Murphy, Grant S., and Maloney, Kevin M.

Published
2021
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12. Use of a Dynamic Flow Platform To Translate a Batch Immobilized Transaminase Process to a Packed Bed Reactor for the Synthesis of an Intermediate of Nemtabrutinib

Author

Di Maso, Michael J., Kuethe, Jeffrey T., Narsimhan, Karthik, Burris, Matthew, Chung, Cheol K., DiBenedetto, Michael, Forstater, Jacob H., Grosser, Shane T., Kuhl, Nadine, Lévesque, François, Maguire, Anne, Maloney, Kevin M., McMullen, Jonathan P., Prier, Christopher K., Qi, Ji, Rivera, Nelo R., Wang, Zhixun, Wyvratt, Brian M., and Zewge, Daniel

Abstract

Herein we describe the translation of an immobilized transaminase process in batch to a packed bed reactor for the synthesis of cyrene amine, an intermediate of Nemtabrutinib. This change in reactor design provided significant benefits in both robustness of the immobilized enzyme preparation and minimization of the amount of the enzyme required to perform the transformation. The extended residence times required for high conversion led us to investigate a dynamic flow system to quickly survey the reaction kinetics under various conditions and to provide approximate residence times for pseudosteady state runs to determine the lifetime of the enzyme. The immobilized enzyme lifetime was assessed and found to provide high levels of conversion for over 100 h of performance. Ultimately, the process was scaled to provide over a kilogram of the desired amine, isolated as a tosylate salt, and further optimization with an evolved enzyme and translation to larger scales is also discussed.

Published
2023
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13. Engineering Hydroxylase Activity, Selectivity, and Stability for a Scalable Concise Synthesis of a Key Intermediate to Belzutifan.

Author

Cheung-Lee WL, Kolev JN, McIntosh JA, Gil AA, Pan W, Xiao L, Velásquez JE, Gangam R, Winston MS, Li S, Abe K, Alwedi E, Dance ZEX, Fan H, Hiraga K, Kim J, Kosjek B, Le DN, Marzijarani NS, Mattern K, McMullen JP, Narsimhan K, Vikram A, Wang W, Yan JX, Yang RS, Zhang V, Zhong W, DiRocco DA, Morris WJ, Murphy GS, and Maloney KM

Subjects
Oxidation-Reduction, Hydroxylation, Biocatalysis, Mixed Function Oxygenases, Indenes
Abstract

Biocatalytic oxidations are an emerging technology for selective C-H bond activation. While promising for a range of selective oxidations, practical use of enzymes catalyzing aerobic hydroxylation is presently limited by their substrate scope and stability under industrially relevant conditions. Here, we report the engineering and practical application of a non-heme iron and α-ketoglutarate-dependent dioxygenase for the direct stereo- and regio-selective hydroxylation of a non-native fluoroindanone en route to the oncology treatment belzutifan, replacing a five-step chemical synthesis with a direct enantioselective hydroxylation. Mechanistic studies indicated that formation of the desired product was limited by enzyme stability and product overoxidation, with these properties subsequently improved by directed evolution, yielding a biocatalyst capable of >15,000 total turnovers. Highlighting the industrial utility of this biocatalyst, the high-yielding, green, and efficient oxidation was demonstrated at kilogram scale for the synthesis of belzutifan., (© 2024 Wiley-VCH GmbH.)

Published
2024
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