50443-10-2Relevant academic research and scientific papers
Enantioselective Allylation of β-Haloacrylaldehydes: Formal Total Syntheses of Pteroenone and Antillatoxin
Koukal, Petr,Ul?, Jan,Ne?as, David,Kotora, Martin
, p. 2110 - 2114 (2016)
A comparative study of the catalytic allylations and crotylations of (E)- and (Z)-haloacrylaldehydes by Lewis bases (chiral N,N′-dioxides) and Br?nsted acids (chiral phosphoric acids) was undertaken. The reactions proceeded with high enantio- and diastereoselectivities with slightly better asymmetric induction observed in the case of N,N′-dioxide catalysis. The formed enantioenriched chiral unsaturated haloalcohols could be considered general building blocks, as they could be used in the syntheses of more complex natural products possessing substituted 1,3-diene fragments. This was exemplified by the formal total syntheses of pteronenone and antillatoxin. A comparative study of allylations and crotylations of (E)- and (Z)-haloacrylaldehydes is undertaken under Lewis base and Br?nsted acid catalysis. The reactions proceed in both cases with high enantio- and diastereoselectivities. The formed chiral unsaturated haloalcohols can be considered as general building blocks, as exemplified by the formal total syntheses of pteronenone and antillatoxin; HBPin = pinacolborane.
Identification of crucial bottlenecks in engineered polyketide biosynthesis
Grote, Marius,Kushnir, Susanna,Pryk, Niclas,M?ller, David,Erver, Julian,Ismail-Ali, Ahmed,Schulz, Frank
, p. 6374 - 6385 (2019/07/10)
The concept of combinatorial biosynthesis promises access to compound libraries based on privileged natural scaffolds. Ever since the elucidation of the biosynthetic pathway towards the antibiotic erythromycin A in 1990, the predictable manipulation of type I polyketide synthase megaenzymes was investigated. However, this goal was rarely reached beyond simplified model systems. In this study, we identify the intermediates in the biosynthesis of the polyether monensin and numerous mutated variants using a targeted metabolomics approach. We investigate the biosynthetic flow of intermediates and use the experimental setup to reveal the presence of selectivity filters in polyketide synthases. These obstruct the processing of non-native intermediates in the enzymatic assembly line. Thereby we question the concept of a truly modular organization of polyketide synthases and highlight obstacles in substrate channeling along the cascade. In the search for the molecular origin of a selectivity filter, we investigate the role of different thioesterases in the monensin gene cluster and the connection between ketosynthase sequence motifs and incoming substrate structures. Furthermore, we demonstrate that the selectivity filters do not apply to new-to-nature side-chains in nascent polyketides, showing that the acceptance of these is not generally limited by downstream modules.
