Full stereochemical determination of ajudazols A and B by bioinformatics gene cluster analysis and total synthesis of ajudazol B by an asymmetric ortholithiation strategy
The stereochemical determination of the potent respiratory chain inhibitors ajudazols A and B and the total synthesis of ajudazol B are reported. Configurational assignment was exclusively based on biosynthetic gene cluster analysis of both ketoreductase domains for hydroxyl-bearing stereocenters an...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
28 November 2012
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| In: |
Journal of the American Chemical Society
Year: 2012, Volume: 134, Issue: 47, Pages: 19362-19365 |
| ISSN: | 1520-5126 |
| DOI: | 10.1021/ja309685n |
| Online Access: | Verlag, Pay-per-use, Volltext: http://dx.doi.org/10.1021/ja309685n Verlag, Pay-per-use, Volltext: https://doi.org/10.1021/ja309685n 
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| Author Notes: | Sebastian Essig, Sebastian Bretzke, Rolf Müller, and Dirk Menche |
| Summary: | The stereochemical determination of the potent respiratory chain inhibitors ajudazols A and B and the total synthesis of ajudazol B are reported. Configurational assignment was exclusively based on biosynthetic gene cluster analysis of both ketoreductase domains for hydroxyl-bearing stereocenters and one of the first predictive enoylreductase alignments for methyl-bearing stereocenters. The expedient total synthesis resulting in unambiguous proof of the predicted stereochemistry involves a short stereoselective approach to the challenging isochromanone stereotriad by an innovative asymmetric ortholithiation strategy, a modular oxazole formation, and a late-stage Z,Z-selective Suzuki coupling. |
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| Item Description: | Gesehen am 29.11.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1520-5126 |
| DOI: | 10.1021/ja309685n |