Bioinspired Asymmetric Total Synthesis of Emeriones A-C

Sven Jänner; Daniel Isak; Yuli Li; Kendall N Houk; Aubry K Miller

doi:10.1002/anie.202205878

Bioinspired Asymmetric Total Synthesis of Emeriones A-C

Angew Chem Int Ed Engl. 2022 Aug 8;61(32):e202205878. doi: 10.1002/anie.202205878. Epub 2022 Jun 28.

Authors

Sven Jänner¹, Daniel Isak¹, Yuli Li², Kendall N Houk³, Aubry K Miller¹

Affiliations

¹ Cancer Drug Development Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
² Department of Chemistry, School of Science, Tianjin University, Tianjin, China.
³ Department of Chemistry and Biochemistry, University of California, Los Angeles, CA, USA.

Abstract

We report asymmetric bioinspired total syntheses of the fungal metabolites emeriones A-C via stereoselective oxidations of two bicyclo[4.2.0]octadiene diastereomers. The central bicyclic scaffolds are prepared in an 8π/6π electrocyclization cascade of a stereodefined pentaene, which contains the fully assembled side chains of the emeriones. The anti-aldol side chain is made using a Paterson-aldol addition, and the epoxide of the dioxabicyclo[3.1.0]hexane side chain via ring-closure onto an oxidized acetal. Our work has enabled the structural revision of emerione C, and resulted in the synthesis of a "missing" family member, which we call emerione D. DFT calculations identified two methyl groups that govern torquoselectivity in the 8π/6π cascade.

Keywords: Biomimetic Synthesis; Cascade Reactions; Electrocyclizations; Polyketides; Total Synthesis.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Cyclization
Oxidation-Reduction
Stereoisomerism*