Traceless Solid-Phase Synthesis of Ketones via Acid-Labile Enol Ethers: Application in the Synthesis of Natural Products and Derivatives.

In solid-phase organic synthesis, Wang resin is traditionally used for the immobilization of acids, alcohols, phenols, and amines. We report the use of Wang resin for the traceless synthesis of ketones via acid-labile enol ethers. We demonstrate the practicality of this synthetic strategy on the solid-phase synthesis of pyrrolidine-2,4-diones, which represent the core structure of several natural products, including tetramic acid.

In Vivo Dearomatization of the Potent Antituberculosis Agent BTZ043 via Meisenheimer Complex Formation.

Nitrobenzothiazinones are among the most potent antituberculosis agents. Herein, we disclose an unprecedented in vivo reduction process that affords Meisenheimer complexes of the clinical candidates BTZ043 and PBTZ169. The reduction is reversible, occurs in all mammalian species investigated, has a profound influence on the in vivo ADME characteristics, and has considerable implications for the design and implementation of clinical studies.

Ring contraction of 2,5-dihydrobenzo[f][1,2,5]thiadiazepine 1,1-dioxides: access to 4H-benzo[b][1,4]thiazine 1,1-dioxides.

We report an efficient synthesis of 4H-benzo[b][1,4]thiazine 1,1-dioxides via unprecedented ring contraction of 2,5-dihydrobenzo[f][1,2,5]thiadiazepine 1,1-dioxides under mild conditions involving carbon-sulfur bond formation. 2,5-Dihydrobenzo[f][1,2,5]thiadiazepine 1,1-dioxides are easily accessible from commercially available building blocks, including Fmoc-protected amino acids, 2-nitrobenzenesulfonyl chlorides, and bromo ketones. Benzothiazine 1,1-dioxides represent pharmacologically relevant derivatives with biological, medicinal, and industrial applications.