Maleidrides, fascinating natural products produced by fungi, are characterized by a central medium-
sized carbocycle fused to one or two maleic anhydride moieties. They can be differentiated into
nonadrides, octadrides, and heptadrides based on their ring size. Biosynthetically, they emerge from the
fusion of two nine-carbon-containing building blocks followed by enzymatic postmodifications.
Maleidrides exhibit various biological activities and potential pharmaceutical applications ranging from
anti-cancer to selective herbicidal activity. The unique structural features and biological profile of
maleidrides have generated great interest in the chemical community. However, only a few chemical
syntheses of nonadrides have been reported so far and octadride natural products are still inaccessible.
This project aims to fill this gap by developing powerful asymmetric syntheses to access several
maleidrides in the chemical laboratory. Our routes were designed to combine state-of-the art transition
metal catalysis with robust organic transformations allowing for maximum flexibility, high efficiency and
minimum waste. The key step involves a powerful intramolecular alkylation approach previously
established in our lab. The developed syntheses will allow us to explore novel chemical space which is
currently unavailable via semi-synthesis or enzymatic methods. This will have a fundamental impact on
the preparation of analogues with deep-seated structural modifications for biological evaluation.
Establishing a synthetic platform to access medium-sized maleidrides will pave the way for detailed
structure-activity relationship studies with important implications for the development of new drugs.