Synthesis of 2,3,6,8-Tetrasubstituted Chromone Scaffolds

A useful and efficient synthetic strategy to 2,3,6,8-tetrasubstituted chromone derivatives has been developed. 2-Aryl/styryl-8-bromo-6-chloro-3-hydroxychromone derivatives were synthesized and used as scaffolds by introducing a variety of substituents in the 3-, 6-, and 8-positions using palladium-m...

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Bibliographic Details
Published in:Journal of organic chemistry 2006-09, Vol.71 (18), p.6863-6871
Main Authors: Dahlén, Kristian, Wallén, Erik A. A, Grøtli, Morten, Luthman, Kristina
Format: Article
Language:English
Subjects:
Chemistry
Chemistry, Organic - methods
Chromones
Chromones - chemistry
Cross-Linking Reagents
Cross-Linking Reagents - chemistry
Exact sciences and technology
Flavones
Flavones - chemistry
Heterocyclic compounds
Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives
Läkemedelskemi
Medicinal Chemistry
methods
Molecular Structure
Organic
Organic chemistry
Palladium
Palladium - chemistry
Peptides
Preparations and properties
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Summary:A useful and efficient synthetic strategy to 2,3,6,8-tetrasubstituted chromone derivatives has been developed. 2-Aryl/styryl-8-bromo-6-chloro-3-hydroxychromone derivatives were synthesized and used as scaffolds by introducing a variety of substituents in the 3-, 6-, and 8-positions using palladium-mediated reactions. Excellent regioselectivity in all positions could be obtained by performing reactions in the 8-position first, in which Stille, Heck, Suzuki, and Sonogashira reactions gave good to excellent yields of product (63−98%). Stille and Heck reactions in the 6-position also gave the desired products in good yields (64−86%). The hydroxy group in the 3-position was activated as a triflate and used in productive Stille reactions (63−94%). This hydroxyl group was also used in O-alkylation reactions with different functionalized alkyl bromides (57−88%). The flavonoids, which are based on the chromone structure, and other related ring systems, have several interesting biological activities. The chromones are also interesting structural scaffolds, and they have for example been designed to be used as mimetics of short peptides. The versatile applicability of chromone derivatives and especially their potential use in drug discovery implicates the importance of access to efficient synthetic routes to such compounds.
ISSN:0022-3263
1520-6904
DOI:10.1021/jo061008f