The complement system is a self-amplifying proteolytic cascade that serves central role in the innate immune system. It is also recognized as an ideal target for treatment of certain inflammatory diseases like C3 glomerulopathies and age-related macular degeneration. Compound 1 was identified from a virtual screen for small molecule ligands of complement component C3b. 1 uniquely blocks downstream activation of complement component C5 (Garcia et al., 2017). The existing approach to synthesize 1 and its related derivatives resulted in very low yielding reactions. In this endeavor we present our efforts leading to the development of a very efficient one-pot synthesis of the desired 3-acetamido phthalides (2). We further extend the approach to synthesize another potentially important class of compounds, 2-carboxycinnamamides (3) from the common intermediate (4) (Figure 1).

Efficient synthetic approach for 3-acetamido phthalides: Complement inhibitor virtual screening hit

2019 Fall National Meeting

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