Publication
This dissertation focuses on the research on the synthesis of lignan families. Lignan derivatives such as podophyllotoxin serve as drug precursors, for example etoposide or teniposide which have been used in the past forty years as anti-cancer therapeutics. In this context, the development of a cheap, sustainable and efficient syntheses of lignan derivatives is valuable for the scientific community, the industry and the society. The development of a blue LEDs-catalyzed transformation from renewable biomass-derived precursors to aryltetralin cyclic ether lignan, dibenzocyclooctadiene lignan and linear tetrahydrofuran lignan derivatives is disclosed. The potential oxidation of several positions matching those of natural lignans during the reaction and the control of the stereoselectivity are discussed. The mechanism essentially goes through single electron oxidation from an acridinium salt under light irradiation, and the reaction pathways divert depending on the additives present in the reaction mixture. The discovery of a copper(I) salt-promoted cascade from α-chloro esters to one isomer of aryltetralin cyclic lactone lignan derivatives is disclosed. It generates a radical which undergoes 5-exo cyclization forming the lactone ring, and second cyclization from the aryl ring follows. The yields are higher with electron-rich aromatics. An iron(III)-mediated cascade from cinnamic acid-derivatives to the same skeleton is reported, being complementary to the first method as it was more suitable for substrates bearing electron-withdrawing groups. The reaction likely goes through a radical cation intermediate. The last part describes the studies of a short total synthesis towards burlemarxione A and burlemarxione B.