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Abstract
The primary aim of this project was to synthesize new heterocyclic dimers of isoflavones and flavones, and investigate various methodologies for their synthesis. The secondary aim of the project was to synthesize some flavonoid natural products.
Dimeric systems were synthesized using various methodologies including acid catalyzed arylation of isoflavanols and flavanols, acid catalyzed dimerization of flavenes, oxidative dimerization, Sonogashira coupling, Ullmann coupling and Suzuki-Miyaura coupling reactions. The acid catalyzed arylation of isoflavanols was found to proceed in a very stereoselective fashion to give trans-4-arylisoflavans in good yield in a single step. However, related flavanols under similar conditions gave mixtures of cis and trans isomers of 4-arylflavans. Interestingly, it was found that appropriately substituted flavenes, upon treatment with acid undergo stereoselective rearrangement and dimerization to give benzopyranobenzopyrans in high yields. A rationale for the rearrangement is proposed and this dimerization was used for the stereoselective synthesis of the natural product dependensin. As part of the project, some polycyclic natural products such as octandrenolone, flemiculosin, 3-deoxy-MS-II and laxichalcone were also synthesized.
Oxidative dimerization of activated isoflavones was found to be very regioselective, and novel isoflavone dimeric systems were synthesized. Related flavones however, failed to undergo dimerization under similar conditions. A probable explanation for high regioselectivity in the case of isoflavones and unreactivity of flavones has been presented. Phenol oxidative coupling was used for the one-step synthesis of another natural product kudzuisoflavone-A from daidzein. Sonogashira coupling was utilized for the synthesis of dimeric systems linked via an acetylic linker. A variety of soflavone isoflavone, flavone-flavone and isoflavone-flavone dimers were synthesized in "one-pot" by this methodology and in excellent yields. Although Ullmann coupling was found not to be suitable for the synthesis of isoflavone or flavone dimers, one-pot Suzuki-Miyaura methodology gave flavone dimers and various other heterocyclic dimers in good yields.