Donohoe, Harris, Burrows and Parker. JACS, 2006, ASAP. DOI: 10.1021/ja0660148.
Oxidation action in this latest JACS from Tim Donohoe, completing the first synthesis of sylvaticin, a potent antitumor agent and nanomolar cytotoxicity target. The focus is, of course, the THF rings, lying four carbons apart, and with neighbouring hydroxyls. Their route hinges upon an interesting oxidative cyclisation, developed within the group and detailed in a previous methodology paper.
The fun begins with the synthesis of the cyclisation substrate, with the bulk of the work done by a pair of AD reaction performed on a commercially avaliable tetraene. Although the yield for this reaction was low, that can be attributed to the isomeric nature of the starting material. Clevage of the alkene was also low-yielding, but recycling the tetraol biproduct increased this, allowing Wittig olefination and completion of the cyclisation precursor.
Cyclisation, as completed in the previous paper, resulted in a excellent yield of the desired product (the notes mention use of
cinammic cinnamic acid as reducing agent – taking Os(VIII) to Os(VI) via dihydroxylation). Creation of the more complex sidechain was completed in six step and reasonable yield, allowing Grubbs II appendage to the related alkene, and completion of the natural product after diimide reduction and deprotection. A great showcase for a top THF-ilysing reaction.