Publications
8 results found
Tang Q, Petchey M, Rowlinson B, et al., 2024, Broad Spectrum Enantioselective Amide Bond Synthetase from Streptoalloteichus hindustanus., ACS Catal, Vol: 14, Pages: 1021-1029, ISSN: 2155-5435
The synthesis of amide bonds is one of the most frequently performed reactions in pharmaceutical synthesis, but the requirement for stoichiometric quantities of coupling agents and activated substrates in established methods has prompted interest in biocatalytic alternatives. Amide Bond Synthetases (ABSs) actively catalyze both the ATP-dependent adenylation of carboxylic acid substrates and their subsequent amidation using an amine nucleophile, both within the active site of the enzyme, enabling the use of only a small excess of the amine partner. We have assessed the ability of an ABS from Streptoalloteichus hindustanus (ShABS) to couple a range of carboxylic acid substrates and amines to form amine products. ShABS displayed superior activity to a previously studied ABS, McbA, and a remarkable complementary substrate specificity that included the enantioselective formation of a library of amides from racemic acid and amine coupling partners. The X-ray crystallographic structure of ShABS has permitted mutational mapping of the carboxylic acid and amine binding sites, revealing key roles for L207 and F246 in determining the enantioselectivity of the enzyme with respect to chiral acid and amine substrates. ShABS was applied to the synthesis of pharmaceutical amides, including ilepcimide, lazabemide, trimethobenzamide, and cinepazide, the last with 99% conversion and 95% isolated yield. These findings provide a blueprint for enabling a contemporary pharmaceutical synthesis of one of the most significant classes of small molecule drugs using biocatalysis.
Burden TJ, Fernandez KPR, Kagoro M, et al., 2023, Coumarin C-H Functionalization by Mn(I) Carbonyls: Mechanistic Insight by Ultra-Fast IR Spectroscopic Analysis, CHEMISTRY-A EUROPEAN JOURNAL, Vol: 29, ISSN: 0947-6539
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- Citations: 1
Eastwood JB, Hammarback LA, Burden TJ, et al., 2023, Understanding Precatalyst Activation and Speciation in Manganese-Catalyzed C-H Bond Functionalization Reactions, ORGANOMETALLICS, Vol: 42, Pages: 1766-1773, ISSN: 0276-7333
Albino M, Burden TJ, Piras CC, et al., 2023, Mechanically Robust Hybrid Gel Beads Loaded with "Naked" Palladium Nanoparticles as Efficient, Reusable, and Sustainable Catalysts for the Suzuki-Miyaura Reaction, ACS SUSTAINABLE CHEMISTRY & ENGINEERING, ISSN: 2168-0485
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- Citations: 2
Hammarback LA, Eastwood JB, Burden TJ, et al., 2022, A comprehensive understanding of carbon-carbon bond formation by alkyne migratory insertion into manganacycles, CHEMICAL SCIENCE, Vol: 13, Pages: 9902-9913, ISSN: 2041-6520
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- Citations: 5
Hammarback LA, Bishop AL, Jordan C, et al., 2022, Manganese-Mediated C-H Bond Activation of Fluorinated Aromatics and the <i>ortho</i>-Fluorine Effect: Kinetic Analysis by <i>In Situ</i> Infrared Spectroscopic Analysis and Time-Resolved Methods, ACS CATALYSIS, Vol: 12, Pages: 1532-1544, ISSN: 2155-5435
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- Citations: 11
Firth JD, Hammarback LA, Burden TJ, et al., 2021, Light- and Manganese-Initiated Borylation of Aryl Diazonium Salts: Mechanistic Insight on the Ultrafast Time-Scale Revealed by Time-Resolved Spectroscopic Analysis, CHEMISTRY-A EUROPEAN JOURNAL, Vol: 27, Pages: 3979-3985, ISSN: 0947-6539
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- Citations: 9
Zhu Z, Wang Z, Jian Y, et al., 2021, Pd-Catalysed carbonylative Suzuki-Miyaura cross-couplings using Fe(CO)<sub>5</sub> under mild conditions: generation of a highly active, recyclable and scalable 'Pd-Fe' nanocatalyst, GREEN CHEMISTRY, Vol: 23, Pages: 920-926, ISSN: 1463-9262
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- Citations: 8
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