Stereoselective Synthesis of the Isomers of Notoincisol A: Assigment of the Absolute Configuration of this Natural Product and Biological Evaluation | Zendy

Lukáš Rýček | Zendy; Vincenzo Ticli | Zendy; Jakob Pyszkowski | Zendy; Simone Latkolik | Zendy; Xin Liu | Zendy; Atanas G. Atanasov | Zendy; Theresa Steinacher | Zendy; Rudolf Bauer | Zendy; Daniela Schuster | Zendy; Verena M. Dirsch | Zendy; Michael Schnürch | Zendy; Margot Ernst | Zendy; Marko D. Mihovilovič | Zendy

Open Access

Stereoselective Synthesis of the Isomers of Notoincisol A: Assigment of the Absolute Configuration of this Natural Product and Biological Evaluation

Author(s) -

Lukáš Rýček,

Vincenzo Ticli,

Jakob Pyszkowski,

Simone Latkolik,

Xin Liu,

Atanas G. Atanasov,

Theresa Steinacher,

Rudolf Bauer,

Daniela Schuster,

Verena M. Dirsch,

Michael Schnürch,

Margot Ernst,

Marko D. Mihovilovič

Publication year - 2018

Publication title -

journal of natural products

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 0.976

H-Index - 139

eISSN - 1520-6025

pISSN - 0163-3864

DOI - 10.1021/acs.jnatprod.8b00439

Subject(s) - allosteric regulation , natural product , stereochemistry , kinetic resolution , chemistry , stereoisomerism , absolute configuration , biological activity , stereoselectivity , receptor , chemical synthesis , docking (animal) , molecule , biochemistry , in vitro , enantioselective synthesis , organic chemistry , catalysis , medicine , nursing

The total syntheses of all stereoisomers of notoincisol A, a recently isolated natural product with potential anti-inflammatory activity, are reported. The asymmetric synthesis was conducted employing a lipase-mediated kinetic resolution, which enables easy access to all required chiral building blocks with the aim of establishing the absolute configuration of the naturally occurring isomer. This was achieved by comparison of optical properties of the isolated compound with the synthetic derivatives obtained. Moreover, an assessment of the biological activity on PPARγ (peroxisome proliferator-activated receptor gamma) as a prominent receptor related to inflammation is reported. Only the natural isomer was found to activate the PPARγ receptor, and this phenomenon could be explained based on molecular docking studies. In addition, the pharmacological profiles of the isomers were determined using the GABA A (gamma-aminobutyric acid A) ion channel receptor as a representative target for allosteric modulation related to diverse CNS activities. These compounds were found to be weak allosteric modulators of the α1β3 and α1β2γ2 receptor subtypes.

The content you want is available to Zendy users.

Already have an account? Click here to sign in.

Having issues? You can contact us here

Accelerating Research