The study of structural modifications on the chroman skeleton resulting from the cycloaddition reactions between ortho-quinone methides and olefinsVarisa Katesampao
( M.Sc. )
Advisor:
Poonsakdi Ploypradith
Abstract
The benzopyrans or chromans are benzene ring-fused pyrans which are the basis of many naturally occurring compounds. The bicyclic heterocyclic structure of chromans is commonly found in a wide variety of biologically active natural products for example, phytotoxic property (alboatrin), anti-malarial activity (dependensin), and antiandrogenic activity (palodesangrens C). Moreover, the 2-arylchroman derivatives or flavans possess a broad range of biological activities such as antioxidant, anti-inflammatory, anti-allergic, anti-microbial, and anticancer. Therefore, developing a synthesis for 2-arylchroman derivatives have attracted considerable growing interests. The construction of chroman core structures were performed via the hetero-Diels-Alder reaction of ortho-quinone methides (o-QMs) as the intermediates which undergo cycloaddition with alkenes such as styrenes to form 2-arylchroman derivatives. This research has focused on the functionalization on the benzene ring that is fused to the pyran ring of the 2-arylchroman products by various organometallic coupling reactions such as Heck, Negishi, Sonogashira, and Suzuki coupling reactions as the key reactions in the funtionalization of 2-arylchromans, especially for further synthesis of several chroman-containing natural products via hetero-Diels-Alder reactions. For example, palodesangrens C, the natural product isolated from the bark of Brosimum rubescens whose structure consists of prenylcoumarin and chalcone derivatives. It showed potent inhibition of binding of 5α-dihydrotestosterone with the androgen receptor. Dependensin, the dimeric flavonoid, exhibited some potent anti-malarial activity. Profisetinidin, a type of condensed tannins, showed important biological activities such as antioxidant and anti-inflammatory activities. Procyanidins possess a broad range of pharmacological properties including anti-inflammatory, and anti-allergic properties. In addition, the gem-difluoromethylenated biflavonoid has anti-oxidant, anti-inflammatory, anti-microbial and anticancer properties.