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

SZCZEPANIK, Pawel Marcin, Andrey MIKHAYLOV, Ondřej HYLSE, Roman KUČERA, Petra DAĎOVÁ, Marek NEČAS, Lukáš KUBALA, Kamil PARUCH and Jakub ŠVENDA. Convergent Assembly of the Tricyclic Labdane Core Enables Synthesis of Diverse Forskolin-like Molecules. Angewandte Chemie International Edition. Wiley, 2023, vol. 62, No 1, p. 1-7. ISSN 1433-7851. Available from: https://dx.doi.org/10.1002/anie.202213183.

Basic information

Original name

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

Authors

SZCZEPANIK, Pawel Marcin (616 Poland, belonging to the institution), Andrey MIKHAYLOV (643 Russian Federation, belonging to the institution), Ondřej HYLSE (203 Czech Republic, belonging to the institution), Roman KUČERA (703 Slovakia, belonging to the institution), Petra DAĎOVÁ (203 Czech Republic, belonging to the institution), Marek NEČAS (203 Czech Republic, belonging to the institution), Lukáš KUBALA (203 Czech Republic, belonging to the institution), Kamil PARUCH (203 Czech Republic, belonging to the institution) and Jakub ŠVENDA (203 Czech Republic, guarantor, belonging to the institution)

Edition

Angewandte Chemie International Edition, Wiley, 2023, 1433-7851

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Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10400 1.4 Chemical sciences

Country of publisher

Germany

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 16.600 in 2022

RIV identification code

RIV/00216224:14310/23:00130237

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.1002/anie.202213183

UT WoS

000892031600001

Keywords in English

Convergent Synthesis; Forskolin; Labdanes; Michael Addition; Olefin Metathesis

Tags

CF PROT, rivok

Tags

International impact, Reviewed

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Abstract

V originále

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.

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Links

EF16_025/0007381, research and development project	Name: Preklinická progrese nových organických sloučenin s cílenou biologickou aktivitou
GJ15-10504Y, research and development project	Name: Příprava unikátních modulátorů adenylyl cyklázy Investor: Czech Science Foundation
LM2018127, research and development project	Name: Česká infrastruktura pro integrativní strukturní biologii (Acronym: CIISB) Investor: Ministry of Education, Youth and Sports of the CR
LM2018130, research and development project	Name: Národní infrastruktura chemické biologie (Acronym: CZ-­OPENSCREEN) Investor: Ministry of Education, Youth and Sports of the CR
MUNI/A/1209/2022, interní kód MU	Name: Molekuly, komplexy, makrocykly a xerogely Investor: Masaryk University, Molecules, complexes, macrocycles, and xerogels