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Synthesis and antifungal activity of novel sclerotiorin analogues.
- Source :
-
Journal of agricultural and food chemistry [J Agric Food Chem] 2012 May 09; Vol. 60 (18), pp. 4480-91. Date of Electronic Publication: 2012 Apr 25. - Publication Year :
- 2012
-
Abstract
- Sclerotiorin 1, first isolated from Penicillium sclerotiorum, has weak antifungal activity and belongs to the azaphilone-type family of natural products. Several series of sclerotiorin analogues were designed and synthesized with the aim of discovering novel fungicides with improved activity. The syntheses involved two key steps, cycloisomerization and then oxidation, and used a simple and efficient Sonogashira cross-coupling reaction to construct the required functionalized precursor. With sclerotiorin as a control, the activities of the newly synthesized analogues were evaluated against seven fungal pathogens, and several promising candidates (compounds 3a₁, 3d₂, 3e₂, 3f₂ and 3k₂) with greater activity and simpler structures than sclerotiorin were discovered. In addition, preliminary structure-activity relationships were studied, which revealed that not only the chlorine or bromine substituent at the 5-position of the nucleus but also the phenyl group at the 3-position and the substituent pattern on it contributed crucially to the observed antifungal activity. Analogues with a methyl substituent at the 1-position have reduced levels of activity, while those with a free hydroxyl group in place of acetoxy at the quaternary center of the bicyclic ring system retain activity.
- Subjects :
- Antiparasitic Agents chemical synthesis
Antiparasitic Agents chemistry
Antiparasitic Agents pharmacology
Benzopyrans pharmacology
Foodborne Diseases prevention & control
Fungicides, Industrial chemistry
Gibberella drug effects
Mitosporic Fungi drug effects
Pythium drug effects
Structure-Activity Relationship
Benzopyrans chemistry
Drug Design
Fungicides, Industrial chemical synthesis
Fungicides, Industrial pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1520-5118
- Volume :
- 60
- Issue :
- 18
- Database :
- MEDLINE
- Journal :
- Journal of agricultural and food chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 22439963
- Full Text :
- https://doi.org/10.1021/jf300610j