Convergent Assembly of the Tricyclic Labdane Core Enables Synthesis of Diverse Forskolin-like Molecules

0569310 - BFÚ 2024 RIV DE eng J - Journal Article
Szczepanik, P. M. - Mikhaylov, A. A. - Hylse, O. - Kučera, R. - Daďová, Petra - Nečas, M. - Kubala, Lukáš - Paruch, K. - Svenda, J.
Convergent Assembly of the Tricyclic Labdane Core Enables Synthesis of Diverse Forskolin-like Molecules.
Angewandte Chemie - International Edition. Roč. 62, č. 1 (2023), č. článku e202213183. ISSN 1433-7851. E-ISSN 1521-3773
Institutional support: RVO:68081707
Keywords : Convergent Synthesis * Forskolin * Labdanes * Michael Addition * Olefin Metathesis
OECD category: Organic chemistry
Impact factor: 16.6, year: 2022
Method of publishing: Open access
https://onlinelibrary.wiley.com/doi/10.1002/anie.202213183

We report a new synthetic strategy for the flexible preparation of forskolin-like molecules. The approach is different from the previously published works and employs a convergent assembly of the tricyclic labdane-type core from pre-functionalized cyclic building blocks. Stereoselective Michael addition enabled the fragment coupling with excellent control over three newly created contiguous stereocenters, all-carbon quaternary centers included. Silyl enol ether-promoted ring-opening metathesis paired with ring closure were the other key steps enabling concise assembly of the tricyclic core. Late-stage functionalization sequences transformed the tricyclic intermediates into a set of different forskolin-like molecules. The modular nature of the synthetic scheme described herein has the potential to become a general platform for the preparation of analogs of forskolin and other complex tricyclic labdanes.
Permanent Link: https://hdl.handle.net/11104/0345676