- Biosynthetically Guided Structure–Activity Relationship Studies of Merochlorin A, an Antibiotic Marine Natural Product
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The onset of new multidrug-resistant strains of bacteria demands continuous development of antibacterial agents with new chemical scaffolds and mechanisms of action. We present the first structure–activity relationship (SAR) study of 16 derivatives of a s
- López-Pérez, Borja,Pepper, Henry P.,Ma, Rong,Fawcett, Benjamin J.,Pehere, Ashok D.,Wei, Qi,Ji, Zengchun,Polyak, Steven W.,Dai, Huanqin,Song, Fuhang,Abell, Andrew D.,Zhang, Lixin,George, Jonathan H.
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- Mechanistic evidence for an α-oxoketene pathway in the formation of β-ketoamides/esters via Meldrum's acid adducts
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A practical, one-pot process for the preparation of β-keto amides via a three-component reaction, including Meldrum's acid, an amine, and a carboxylic acid, has been developed. Key to development of an efficient, high-yielding process was an in-depth understanding of the mechanism of the multistep process. Kinetic studies were carried out via online IR monitoring and subsequent principal component analysis which provided a means of profiling the concentration of both the anionic and free acid forms of the Medrum's adduct 6 in real time. These studies, both in the presence and absence of nucleophiles, strongly suggest that formation of β-keto amides from acyl Meldrum's acids occurs via α-oxoketene species 2 and rule out other possible reaction pathways proposed in the literature, such as via protonated α-oxoketene intermediates 3 or nucleophilic addition-elimination pathways.
- Xu, Feng,Armstrong III, Joseph D.,Zhou, George X.,Simmons, Bryon,Hughes, David,Ge, Zhihong,Grabowski, Edward J. J.
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- Biomimetic total synthesis of (±)-merochlorina
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Inspired: The proposed biosynthetic pathway toward the potent antibiotic meroterpenoid (±)-merochlorinA inspired its concise total synthesis. The key steps in the synthesis are a one-pot aromatization-alkylation reaction, followed by a biomimetic oxidativ
- Pepper, Henry P.,George, Jonathan H.
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- Biomimetic synthesis of (±)-merochlorin B
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A short total synthesis, guided by biosynthetic considerations, of racemic merochlorin B is presented. The formation of its isomer, merochlorin A, was not observed under the conditions. Key steps include a directed ortho-metalation (DoM), a selective demethylation, an ortho-allylation, and an oxidative [3 + 2]-cycloaddition mediated by an iodine(III) reagent.
- Meier, Robin,Strych, Sebastian,Trauner, Dirk
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p. 2634 - 2637
(2014/06/09)
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