Ma, Tsz-KanTsz-KanMaParsons, Philip JamesPhilip JamesParsonsBarrett, Anthony GMAnthony GMBarrett2019-05-172019-05-172019-05-03The Journal of Organic Chemistry, 2019, 84 (9), pp.4961-49700022-3263http://hdl.handle.net/10044/1/69726The first total synthesis of five austalide natural products, (±)-17S-dihydroaustalide K, (±)-austalide K, (±)-13-deacetoxyaustalide I, (±)-austalide P, and (±)-13-deoxyaustalide Q acid, was accomplished via a series of biomimetic transformations. Key steps involved polyketide aromatization of a trans,trans-farnesol-derived β,δ-diketodioxinone into the corresponding β-resorcylate, followed by titanium(III)-mediated reductive radical cyclization of an epoxide to furnish the drimene core. Subsequent phenylselenonium ion induced diastereoselective cyclization of the drimene completed the essential carbon framework of the austalides to access (±)-17S-dihydroaustalide K, (±)-austalide K, and (±)-13-deacetoxyaustalide I via sequential oxidations. Furthermore, (±)-13-deacetoxyaustalide I could serve as a common intermediate to be derivatized into other related natural products, (±)-austalide P and (±)-13-deoxyaustalide Q acid, by functionalizing the cyclic lactone moiety.© 2019 American Chemical Society. ACS AuthorChoice - This is an open access article published under a Creative Commons Attribution (CC-BY) License (https://pubs.acs.org/page/policy/authorchoice_ccby_termsofuse.html), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.0304 Medicinal and Biomolecular Chemistry0305 Organic Chemistry0302 Inorganic ChemistryOrganic ChemistryJournal Articlehttps://www.dx.doi.org/10.1021/acs.joc.9b00142EP/N022815/11520-6904