A synthesis-enabled relative configurational assignment of the C31-C46 region of hemicalide.
Stockdale, Tegan P
Lam, Nelson YS https://orcid.org/0000-0002-9307-0619
Paterson, Ian https://orcid.org/0000-0002-8861-9136
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.
Online Publication Date
Antineoplastic Agents, Magnetic Resonance Spectroscopy, Polyketides, Stereoisomerism
Chem Commun (Camb)
Royal Society of Chemistry (RSC)