1460-05-5Relevant articles and documents
β-Lactone formation during product release from a nonribosomal peptide synthetase
Schaffer, Jason E,Reck, Margaret R,Prasad, Neha K,Wencewicz, Timothy A
, p. 737 - 744 (2017)
Nonribosomal peptide synthetases (NRPSs) are multidomain modular biosynthetic assembly lines that polymerize amino acids into a myriad of biologically active nonribosomal peptides (NRPs). NRPS thioesterase (TE) domains employ diverse release strategies for off-loading thioester-tethered polymeric peptides from termination modules typically via hydrolysis, aminolysis, or cyclization to provide mature antibiotics as carboxylic acids/esters, amides, and lactams/lactones, respectively. Here we report the enzyme-catalyzed formation of a highly strained β-lactone ring during TE-mediated cyclization of a β-hydroxythioester to release the antibiotic obafluorin (Obi) from an NRPS assembly line. The Obi NRPS (ObiF) contains a type I TE domain with a rare catalytic cysteine residue that plays a direct role in β-lactone ring formation. We present a detailed genetic and biochemical characterization of the entire Obi biosynthetic gene cluster in plant-associated Pseudomonas fluorescens ATCC 39502 that establishes a general strategy for β-lactone biogenesis.
Preparation method of mirabegron
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Page/Page column 5-8, (2019/04/30)
The invention discloses a preparation method of mirabegron, and the method comprises: S1, carrying out reduction reaction on p-nitrophenylacetonitrile to obtain p-nitrophenylacetaldehyde; S2, carryingout condensation reduction on the p-nitrophenylacetaldehyde and (R) 2-amino-1-phenethyl alcohol to obtain (R) 2-(4-nitrophenethyl) amino)-1-phenyl ethyl alcohol; S3, carrying out reduction on the (R)2-amino-1-phenethyl alcohol to obtain (R) 2-(4-nitrophenethyl) amino)-1-phenyl ethyl alcohol to obtain an intermediate (R) 2-((4-aminophenyl ethyl) amino)-1-phenyl ethyl alcohol; and S4, carrying outcondensation on the (R) 2-((4-aminophenyl ethyl) amino)-1-phenyl ethyl alcohol and aminothiazole acetic acid to obtain the mirabegron. According to the method, the starting raw materials are cheap and easy to obtain, the reaction conditions are controllable, the synthetic route steps are few, the yield is high, the cost is low, and the prepared mirabegron is high in purity.
Facile Access to Challenging ortho-Terphenyls via Merging Two Multi-Step Domino Reactions in One-Pot: A Joint Experimental/Theoretical Study
Grau, Benedikt W.,B?nisch, Simon,Neuhauser, Alexander,Hampel, Frank,G?rling, Andreas,Tsogoeva, Svetlana B.
, p. 3982 - 3992 (2019/08/08)
ortho-Terphenyls are of high interest for medicinal chemistry and materials science, but they are difficult to access. Herein, we demonstrate a straightforward and sustainable synthesis of highly functionalized ortho-terphenyls via joining an organocatalyzed two-step domino reaction (Knoevenagel/vinylogous Michael) with a DABCO/CuBr2 co-catalyzed three-step domino reaction (cyclization/tautomerization/aromatization) in a one-pot process. Overcoming necessity to isolate intermediate products leads to a reduction of energy, costs and waste for a broad scope of reactions. DFT calculations have been performed to investigate the thermodynamics of this one-pot process towards ortho-terphenyls and to study the reaction profile of the vinylogous Michael reaction under inclusion of solvent effects. Role of London dispersion forces in this transformation has been elucidated. It is shown that reaction kinetics and thermodynamics are slightly influenced by dispersion interactions. Furthermore, the addition of dispersion energy donors leads to small changes of reaction energies in some cases.
