Isolation and total synthesis of gymnastatin N, a POLO-like kinase 1 active constituent from the fungus Arachniotus punctatus

Phoon, Chee Wee, Somanadhan, Brinda, Heng, Sabrina Cher Hui, Ngo, Anna, Ng, Siew Bee, Butler, Mark S., Buss, Antony D. and Sim, Mui Mui (2004) Isolation and total synthesis of gymnastatin N, a POLO-like kinase 1 active constituent from the fungus Arachniotus punctatus. Tetrahedron, 60 50: 11619-11628. doi:10.1016/j.tet.2004.09.046


Author Phoon, Chee Wee
Somanadhan, Brinda
Heng, Sabrina Cher Hui
Ngo, Anna
Ng, Siew Bee
Butler, Mark S.
Buss, Antony D.
Sim, Mui Mui
Title Isolation and total synthesis of gymnastatin N, a POLO-like kinase 1 active constituent from the fungus Arachniotus punctatus
Formatted title
Isolation and total synthesis of gymnastatin N, a POLO-like kinase 1 active constituent from the fungus Arachniotus punctatus
Journal name Tetrahedron   Check publisher's open access policy
ISSN 0040-4020
1464-5416
Publication date 2004-12-06
Sub-type Article (original research)
DOI 10.1016/j.tet.2004.09.046
Volume 60
Issue 50
Start page 11619
End page 11628
Total pages 10
Place of publication Oxford
Publisher Pergamon Press
Language eng
Subject 0305 Organic Chemistry
Formatted abstract
A high throughput screen against POLO-like kinase 1 (Plk1), an anti-cancer target, identified an active extract from the fungus Arachniotus punctatus. Bioassay guided fractionation led to the isolation of the new natural product, gymnastatin N (1) and the known compound aranorosinol A (2) with IC50 values of 13 and 118 μM, respectively. A 12′-hydroxy analog of gymnastatin N, 3, was also isolated as a minor component. Gymnastatin N (1) was found to be a 52:48 mixture of (1S,6′R) and (1R,6′R) diastereomers, by synthesis of the four possible diastereomers and comparison of the optical rotation and chiral HPLC profile of each diastereoisomer with the natural product. Analogues of 1 were synthesized and evaluated against the Plk1 assay and these SAR studies suggested that the diene and free carboxylic acid moieties might be responsible for its bioactivity. Graphical Abstract.
© 2004 Elsevier Ltd. All rights reserved.
Keyword 12' hydroxygymnastatin
Alkadiene
Antiinfective agent
Antineoplastic agent
Aranorosinol
Carboxylic acid
Gymnastatin
Phosphotransferase
Unclassified drug
Diastereoisomer
Fungus
High performance liquid chromatography
High throughput screening
Isolation procedure
Optical rotation
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
Institute for Molecular Bioscience - Publications
 
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Created: Tue, 23 Mar 2010, 08:59:47 EST by June Temby on behalf of Institute for Molecular Bioscience