Enantioselective Total Synthesis of (–)‐Psiguadial A

L Liam P. O'Grady (Department of Chemistry & Biochemistry University of Delaware 163 The Green Newark Delaware 19716 USA) M Marcel Achtenhagen (Department of Chemistry & Biochemistry University of Delaware 163 The Green Newark Delaware 19716 USA) M Michael F. Wisthoff (Department of Chemistry & Biochemistry University of Delaware 163 The Green Newark Delaware 19716 USA) R Robert S. Lewis (Department of Chemistry & Biochemistry University of Delaware 163 The Green Newark Delaware 19716 USA) K Katarina Pfeifer W Weifeng Zheng (Department of Chemistry & Biochemistry University of Delaware 163 The Green Newark Delaware 19716 USA) M Maxwell I. Martin (Department of Chemistry & Biochemistry University of Delaware 163 The Green Newark Delaware 19716 USA) G Glenn P. A. Yap (Department of Chemistry and Biochemistry) W William J. Chain (Department of Chemistry & Biochemistry University of Delaware 163 The Green Newark Delaware 19716 USA)

Abstract

Abstract The first enantioselective total synthesis of the antiproliferative natural product (–)‐psiguadial A is reported. This approach features the enantioselective synthesis of a complex tricyclic terpenoid precursor, the union of that precursor with a polyketide component by an enolate‐ ortho ‐quinone methide coupling reaction to form a highly congested carbon─carbon bond, and an acid‐mediated intramolecular hydration ring‐closure leveraging a fully substituted alkene to generate the unique oxepane core structure of the natural product.

Article Details

Volume / Issue Vol. 64, Issue 30
Published July 21, 2025
ISSN 1433-7851
Publisher Wiley

Journal Info

Angewandte Chemie International Edition

Wiley

ISSN: 1433-7851 Physical Sciences

Authors (9)

L

Liam P. O'Grady

Department of Chemistry & Biochemistry University of Delaware 163 The Green Newark Delaware 19716 USA

M

Marcel Achtenhagen

Department of Chemistry & Biochemistry University of Delaware 163 The Green Newark Delaware 19716 USA

M

Michael F. Wisthoff

Department of Chemistry & Biochemistry University of Delaware 163 The Green Newark Delaware 19716 USA

R

Robert S. Lewis

Department of Chemistry & Biochemistry University of Delaware 163 The Green Newark Delaware 19716 USA

K

Katarina Pfeifer

W

Weifeng Zheng

Department of Chemistry & Biochemistry University of Delaware 163 The Green Newark Delaware 19716 USA

M

Maxwell I. Martin

Department of Chemistry & Biochemistry University of Delaware 163 The Green Newark Delaware 19716 USA

G

Glenn P. A. Yap

Department of Chemistry and Biochemistry

W

William J. Chain

Department of Chemistry & Biochemistry University of Delaware 163 The Green Newark Delaware 19716 USA