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Published on: July 6, 2016
A synthesis-enabled relative configurational assignment of the C31-C46 region of hemicalide
Tegan P Stockdale1, Nelson Y S Lam1, Ian Paterson1
1Yusuf Hamied Department of Chemistry, Lensfield Road, Cambridge, CB2 1EW, UK.
Abstract:
With 21 unknown stereocentres embedded in spatially separated stereoclusters, the cytotoxic polyketide hemicalide represents a seemingly intractible structural assignment problem. Herein, through the targeted synthesis of configurationally defined fragments, as well as "encoded" mixtures of diastereomers, the stereochemical elucidation of the C31-C46 region of hemicalide is achieved. Detailed NMR spectroscopic analysis of candidate fragments and comparison with the related hemicalide data strongly supported a 31,32-syn, 32,36-anti and 42,46-anti relationship. In combination with previous work on hemicalide, this reduces the number of possible structural permutations down to a more manageable eight diastereomers.
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