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A gold-catalyzedsynthesis of cyclic 2-oxodienes from readily preparedpropargyl alcohols and the subsequent Diels–Alder reactionare reported. The dehydrative cyclization reactions proceeded smoothly,and the dienes formed in situ were demonstrated to undergo cycloadditionwith a variety of dienophiles. This method offers a new strategy forthe synthesis of indolocarbazole alkaloids, whereby the convergentsynthetic design allows for differentiation between the indole nitrogens. [ABSTRACT FROM AUTHOR]

DHODH inhibition represents an attractive approach to overcome differentiation blockade for the treatment of AML. In a previous communication, we described our efforts leading to the discovery of compound 3 (JNJ-74856665), an orally bioavailable, potent, and selective DHODH inhibitor for clinical development. Guided by the co-crystal structures bound to human DHODH, other fused six-membered constructs were explored as isosteric replacements of the isoquinolinone central core. The correct positioning of the nitrogen in these core systems proved to be essential in modulating potency. Herein is described the synthesis of these complexly functionalized cores and their profiling, leading to DHODH inhibitors that possess favorable properties suitable for further development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

The first catalytic enantioselective alkynylation of chromones is reported. In this process, chromones are silylated to form silyloxybenzopyrylium ions that lead to silyl enol ethers after Cu-catalyzed alkyne addition using StackPhos as a ligand. The outcome of the reaction is impacted by distal ligand substituents with differing electronic character and it was found that successful reactions could be achieved with different ligand congeners by using different solvents. This sequence enables access to different products by protonation or further functionalization, thus increasing complexity in a divergent manner. The transformation is high yielding over a broad scope to provide a variety of useful chromanones in high enantioselectivity., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)