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
-
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.
Copper-Catalyzed Ring-Opening/Reconstruction of Anthranils with Oxo-Compounds: Synthesis of Quinoline Derivatives
Zou, Liang-Hua,Zhu, Hao,Zhu, Shuai,Shi, Kai,Yan, Cheng,Li, Ping-Gui
, p. 12301 - 12313 (2019/10/11)
A copper-catalyzed protocol for the construction of various 2-aryl(alkyl)-3-acylquinolines or 3-arylquinolines using readily available anthranils and 1,3-diketones or aldehydes as starting materials is reported herein. Dioxygen as the sole oxidant and hexafluoroisopropanol as the solvent play an important role in both procedures. This ring-opening/reconstruction strategy involving N-O bond cleavage and C-N/C-C bond formation features high yields and broad substrate scope.