The benzannulated spiroketal motif is found in a variety of natural products and exhibits a wide array of biological activity, including known function as anticancer and antimicrobial agents. Although these compounds hold promise as potential therapeutics for a variety of disease types, benzannulated spiroketals are underrepresented as possible drug candidates. Using methodology developed in our laboratory, a scalable synthesis of diastereomeric benzannulated 5,5-spiroketals has been utilized for the preparation of a 100-member pilot library. A sparse matrix virtual library design, based on applying a maximum dissimilarity method, was implemented to select library members for chemical synthesis. Furthermore, a cheminformatic analysis of the pilot library reveals that these compounds occupy chemical space distinct from synthesis drugs. This structural and physicochemical diversity can be advantageous for drug discovery. An evaluation of the library members in screening assays will reveal their potential applicability as drug candidates.

Design, synthesis, and biological evaluation of a benzannulated spiroketal pilot library

253rd National Meeting (2017)

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