Synthesis of novel flavones and isoflavones

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Copyright: Devakaram, Ruth Vandana
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Abstract
The primary aim of this project is to synthesize new heterocyclic compounds derived from flavones and isoflavones and thereby, to investigate various methodologies for their synthesis. The biflavonoid, dependensin was a major focus of our study since the benzopyrano[4,3-b]benzopyran ring system present in the natural product was unique and hence, desirable for biological applications. We targeted the acid-catalyzed reactions of 5-methoxy-, 6-methoxy- and 7-methoxyflavenes and found the dimerization to be dependent on the position of the methoxy substituent in the flavene ring. A series of benzopyrano[4,3-b]benzopyrans was generated from the acid-catalyzed reactions of 7-methoxyflavenes and 5,7,8-trimethoxyflavenes. Interestingly, the acid-catalyzed reactions attempted on 5-methoxy- and 6-methoxyflavenes were found to undergo dimerization differently to yield a novel range of biflavonoids containing the tetrahydrochromeno[2,3-b]chromene ring system. A plausible mechanism for the observed rearrangement has also been proposed. The effect of various acids used as catalysts on the dimerization reactions has been evaluated and discussed in this thesis. Similarly, the acid-catalyzed dimerization reactions on isoflavanols and their corresponding isoflavenes were studied in depth and dimerization was found to be dependent on the presence of electron rich substituents in ring B of the isoflavanols and also in performing the reaction in very cold conditions. A probable rationale to this rearrangement has been described. The widespread applications of Mannich bases in medicinal chemistry are noteworthy. Hence, another part of the project was to study the Mannich reactions on flavones using various primary and secondary amines, aminals and amino acids and to probe into the regioselectivity and chemoselectivity of the products obtained. The key point of interest to note was the site of activation in the flavone ring, which was C5 in 6-hydroxyflavones and C8 in 7-hydroxyflavones. The primary amines yielded benzoxazines whereas the secondary amines, aminals and amino acids yielded simple Mannich bases. Further, the benzoxazines were found to undergo cleavage to generate the corresponding simple Mannich bases. Our research group has previously worked on the synthesis of a series of 4-arylflavans and 4-arylisoflavans, but however, there are no reports on the synthesis of 4-arylazaflavans in the literature. Hence, 4-arylazaflavans were synthesized via the acid-catalyzed reactions of azaflavanols with nucleophiles such as naphthol and dimethoxyphenol, whereas 4-heteroarylazaflavans were obtained using heterocycles such as furan, indoles and isoflavenes. Attempts were made to synthesize the corresponding azaflavenes with the primary aim on subjecting them to acid-catalyzed dimerization reactions similar to the flavenes. However, the dominant product isolated was the corresponding quinoline in all cases. Several experiments were conducted in order to oxidize the 4-arylazaflavans to the corresponding quinolines. The optimum conditions were achieved with the use of iodine as catalyst. This introduces a new strategy to the synthesis of 2,4-disubstituted quinolines.
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Author(s)
Devakaram, Ruth Vandana
Supervisor(s)
Kumar, Naresh
Black, David
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Publication Year
2011
Resource Type
Thesis
Degree Type
PhD Doctorate
UNSW Faculty
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