A comprehensive review of ROS-activated produg strategies for targeted therapy, including state-of-the-art and future perspectives.

Fragment‐based drug discovery (FBDD) has become an established approach for the generation of early lead candidates. However, despite its success and inherent advantages, hit‐to‐candidate progression for FBDD is not necessarily faster than that of traditional high‐throughput screening. Thus, new technology‐driven library design strategies have emerged as a means to facilitate more efficient fragment screening and/or subsequent fragment‐to‐hit chemistry. This minireview discusses such strategies, which cover the use of labeled fragments for NMR spectroscopy, X‐ray crystallographic screening of specialized fragments, covalent linkage for mass spectrometry, dynamic combinatorial chemistry, and fragments optimized for easy elaboration.

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Herein, we describe the natural product inspired synthesis of 38 complex small molecules based upon 20 unique frameworks suitable for fragment-based screening.

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Efficient access to diverse screening compounds with desirable, lead‐like properties can be a bottleneck in early drug discovery and chemical biology. Herein we present an efficient, rapid route to three structurally distinct classes of compounds (A–C) from a single precursor, which in turn is available through a one‐pot Petasis 3‐component reaction/Diels–Alder cascade reaction. We demonstrate the versatility of the approach through the synthesis of 35 exemplary compounds from the three classes, as well as by the production of 2188 final compounds, which have been included in the Joint European Compound Library of the European Lead Factory.

 Users may download and print one copy of any publication from the public portal for the purpose of private study or research.  You may not further distribute the material or use it for any profit-making activity or commercial gain  You may freely distribute the URL identifying the publication in the public portal If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.

Recent reports of antiepileptic activity of the fungal alkaloid TMC-120B have renewed the interest in this natural product. Previous total syntheses of TMC-120B comprise many steps and have low overall yields (11–17 steps, 1.5–2.9% yield). Thus, to access this compound more efficiently, we herein present a concise and significantly improved total synthesis of the natural product. Our short synthesis relies on two key cyclization steps to assemble the central scaffold: isoquinoline formation via an ethynyl-imino cyclization and an intramolecular Friedel-Crafts reaction to form the furanone.