Meroterpenoid synthesis via sequential polyketide aromatization and radical anion cascade triene cyclization: Biomimetic total syntheses of austalide natural products
File(s)acs.joc.9b00142.pdf (1.13 MB)
Published version
Author(s)
Ma, Tsz-Kan
Parsons, Philip James
Barrett, Anthony GM
Type
Journal Article
Abstract
The 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.
Date Issued
2019-05-03
Date Acceptance
2019-04-01
Citation
The Journal of Organic Chemistry, 2019, 84 (9), pp.4961-4970
ISSN
0022-3263
Publisher
American Chemical Society (ACS)
Start Page
4961
End Page
4970
Journal / Book Title
The Journal of Organic Chemistry
Volume
84
Issue
9
Copyright Statement
© 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.
Sponsor
Engineering & Physical Science Research Council (EPSRC)
Grant Number
EP/N022815/1
Subjects
0304 Medicinal and Biomolecular Chemistry
0305 Organic Chemistry
0302 Inorganic Chemistry
Organic Chemistry
Publication Status
Published
Date Publish Online
2019-04-02