2382-59-4Relevant articles and documents
Asymmetric Total Synthesis of the Naturally Occurring Antibiotic Anthracimycin
Brimble, Margaret A.,Davison, Emma K.,Freeman, Jared L.,Furkert, Daniel P.,Wuest, William M.,Zhang, Wanli
, (2020)
The first total synthesis of the potent antibiotic anthracimycin was achieved in 20 steps. The synthesis features an intramolecular Diels-Alder reaction to forge the trans-decalin moiety, and an unprecedented aldol reaction using a complex β-ketoester to provide the tricarbonyl motif. A Stork-Zhao olefination and Grubbs ring closing metathesis delivered the E/Z-diene and forged the macrocycle. The C2 configuration was set with a base-mediated epimerization, providing access to (-)-anthracimycin.
Preparation of Acidic 5-Hydroxy-1,2,3-triazoles via the Cycloaddition of Aryl Azides with β-Ketoesters
Pacifico, Roberta,Destro, Dario,Gillick-Healy, Malachi W.,Kelly, Brian G.,Adamo, Mauro F. A.
, p. 11354 - 11360 (2021/08/20)
Herein, a high-yielding cycloaddition reaction of β-ketoesters and azides to provide 1,2,3-triazoles is described. The reactions employing 2-unsubstituted β-ketoesters were found to provide 5-methyl-1,2,3-triazoles, whereas 2-alkyl-substituted β-ketoester
Discovery and Engineering of Pathways for Production of α-Branched Organic Acids
Blaisse, Michael R.,Dong, Hongjun,Fu, Beverly,Chang, Michelle C. Y.
supporting information, p. 14526 - 14532 (2017/10/24)
Cell-based synthesis offers many opportunities for preparing small molecules from simple renewable carbon sources by telescoping multiple reactions into a single fermentation step. One challenge in this area is the development of enzymatic carbon-carbon bond forming cycles that enable a modular disconnection of a target structure into cellular building blocks. In this regard, synthetic pathways based on thiolase enzymes to catalyze the initial carbon-carbon bond forming step between acyl coenzyme A (CoA) substrates offer a versatile route for biological synthesis, but the substrate diversity of such pathways is currently limited. In this report, we describe the identification and biochemical characterization of a thiolase-ketoreductase pair involved in production of branched acids in the roundworm, Ascaris suum, that demonstrates selectivity for forming products with an α-methyl branch using a propionyl-CoA extender unit. Engineering synthetic pathways for production of α-methyl acids in Escherichia coli using these enzymes allows the construction of microbial strains that produce either chiral 2-methyl-3-hydroxy acids (1.1 ± 0.2 g L-1) or branched enoic acids (1.12 ± 0.06 g L-1) in the presence of a dehydratase at 44% and 87% yield of fed propionate, respectively. In vitro characterization along with in vivo analysis indicates that the ketoreductase is the key driver for selectivity, forming predominantly α-branched products even when paired with a thiolase that highly prefers unbranched linear products. Our results expand the utility of thiolase-based pathways and provide biosynthetic access to α-branched compounds as precursors for polymers and other chemicals.
