A Concise Synthesis of Forskolin

Ondřej Hylse; Lukáš Maier; Roman Kučera; Tomáš Perečko; Aneta Svobodová; Lukáš Kubala; Kamil Paruch; Jakub Švenda

doi:10.1002/anie.201706809

A Concise Synthesis of Forskolin

Angew Chem Int Ed Engl. 2017 Oct 2;56(41):12586-12589. doi: 10.1002/anie.201706809. Epub 2017 Sep 5.

Authors

Ondřej Hylse^{1

2}, Lukáš Maier^{1

2}, Roman Kučera¹, Tomáš Perečko^{2

3}, Aneta Svobodová^{2

3}, Lukáš Kubala^{2

3}, Kamil Paruch^{1

2}, Jakub Švenda^{1

2}

Affiliations

¹ Department of Chemistry, Masaryk University, Kamenice 5, Brno, 625 00, Czech Republic.
² International Clinical Research Center, St. Anne's University Hospital, Pekařská 53, Brno, 656 91, Czech Republic.
³ Institute of Biophysics, Academy of Sciences of the Czech Republic, Královopolská 135, Brno, 612 65, Czech Republic.

PMID: 28782270
DOI: 10.1002/anie.201706809

Abstract

A 24-step synthesis of (±)-forskolin is presented, which delivered hundred milligram quantities of this complex diterpene in one pass. Transformations key to our approach include: a) a strategic allylic transposition, b) stepwise assembly of a sterically encumbered isoxazole ring, and c) citric acid-modified Upjohn dihydroxylation of a resilient tetrasubstituted olefin. The developed route has exciting potential for the preparation of new forskolin analogues inaccessible by semisynthesis.

Keywords: adenylyl cyclases; forskolin; natural product synthesis; structural analogues.

Publication types

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