Dataset Information

18O assisted analysis of a ?,?-epoxyketone cyclization: synthesis of the C16-C28 fragment of ammocidin D.

ABSTRACT: The C16-C28 fragment common to the cytotoxic macrolide ammocidin D has been prepared by a stereospecific 5-exo closure of a ?,?-epoxyketone followed by a rearrangement to a pyran acetal. The reaction pathway was traced by (18)O labeling of the keto carbonyl and observation of (18)O induced (13)C shifts in the pyran acetal product. NMR data of the synthetic C16-C28 fragment compared favorably to the natural product providing support of the assigned stereochemistry.

SUBMITTER: Chau ST

PROVIDER: S-EPMC3079550 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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18O assisted analysis of a γ,δ-epoxyketone cyclization: synthesis of the C16-C28 fragment of ammocidin D.

Chau Stephen T ST Hayakawa Yoichi Y Sulikowski Gary A GA

Organic letters 20110119 4

The C16-C28 fragment common to the cytotoxic macrolide ammocidin D has been prepared by a stereospecific 5-exo closure of a γ,δ-epoxyketone followed by a rearrangement to a pyran acetal. The reaction pathway was traced by (18)O labeling of the keto carbonyl and observation of (18)O induced (13)C shifts in the pyran acetal product. NMR data of the synthetic C16-C28 fragment compared favorably to the natural product providing support of the assigned stereochemistry. ...[more]

PMID: 21247077

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Project description:Next-generation screening of disease-related metabolomic phenotypes requires monitoring of both metabolite levels and turnover rates. Stable isotope (18)O-assisted (31)P nuclear magnetic resonance (NMR) and mass spectrometry uniquely allows simultaneous measurement of phosphometabolite levels and turnover rates in tissue and blood samples. The (18)O labeling procedure is based on the incorporation of one (18)O into P(i) from [(18)O]H(2)O with each act of ATP hydrolysis and the distribution of (18)O-labeled phosphoryls among phosphate-carrying molecules. This enables simultaneous recording of ATP synthesis and utilization, phosphotransfer fluxes through adenylate kinase, creatine kinase, and glycolytic pathways, as well as mitochondrial substrate shuttle, urea and Krebs cycle activity, glycogen turnover, and intracellular energetic communication. Application of expanded (18)O-labeling procedures has revealed significant differences in the dynamics of G-6-P[(18)O] (glycolysis), G-3-P[(18)O] (substrate shuttle), and G-1-P[(18)O] (glycogenolysis) between human and rat atrial myocardium. In human atria, the turnover of G-3-P[(18)O], which defects are associated with the sudden death syndrome, was significantly higher indicating a greater importance of substrate shuttling to mitochondria. Phosphometabolomic profiling of transgenic hearts deficient in adenylate kinase (AK1-/-), which altered levels and mutations are associated to human diseases, revealed a stress-induced shift in metabolomic profile with increased CrP[(18)O] and decreased G-1-P[(18)O] metabolic dynamics. The metabolomic profile of creatine kinase M-CK/ScCKmit-/--deficient hearts is characterized by a higher G-6-[(18)O]P turnover rate, G-6-P levels, glycolytic capacity, ?/?-phosphoryl of GTP[(18)O] turnover, as well as ?-[(18)O]ATP and ?-[(18)O]ADP turnover, indicating altered glycolytic, guanine nucleotide, and adenylate kinase metabolic flux. Thus, (18)O-assisted gas chromatography-mass spectrometry and (31)P NMR provide a suitable platform for dynamic phosphometabolomic profiling of the cellular energetic system enabling prediction and diagnosis of metabolic diseases states.

Dataset Information

18O assisted analysis of a ?,?-epoxyketone cyclization: synthesis of the C16-C28 fragment of ammocidin D.

Publications

18O assisted analysis of a γ,δ-epoxyketone cyclization: synthesis of the C16-C28 fragment of ammocidin D.

Similar Datasets

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