Synthesis and antibacterial study of anhydrotetracycline derivatives.

A novel and new type of tetracycline with a different mechanism of action was necessary, due to the drug resistance of existing tetracyclines. This study outlines the synthesis and antibacterial evaluation of anhydro-tetracycline derivatives, which are unconventional tetracyclines with unique mechanisms of action. These derivatives include C4-NH, C4-OH, and C9-substituted variations, and our synthetic approach focuses on semi-synthesis using natural tetracyclines as the starting precursors.

Advances in [4+3]-Annulation/Cycloaddition Reactions Leading to Homo- and Heterocycles with Seven-Membered Rings.

In this review, we summarize advances in [4+3] and a few other annulation/cycloaddition reactions for the construction of seven membered rings, with an emphasis on the literature subsequent to the year 2010. The type of products include the following: azepines, diazepines, benzazepinones, 1,2-diazepinones, oxazepinones, benzothiazepines, benzodiazepinones, benzoxopinones, cyclohepta[b]indoles, benzoxazepines, azepino-indoles, oxepines/oxazepanes, triazepines oxepinoindolones/azepinoindolones, oxadiazepines, azabicyclooctanes. Emphasis is also given to cover diverse types of annulations; possible intermediates are displayed in the illustrated schemes to aid future work.

Reaction of Indole Carboxylic Acid/Amide with Propargyl Alcohols: [4 + 3]-Annulation, Unexpected 3- to 2- Carboxylate/Amide Migration, and Decarboxylative Cyclization.

1-Methylindole-3-carboxamides react with substituted propargyl alcohols to afford lactams by [4 + 3]-annulation and carboxamide group migration to the indole-2-position. In contrast, indole-2-carboxylic acids/amides form fused seven-membered lactones/lactams (oxepinoindolones/azepinoindolones) upon treatment with substituted propargyl alcohols using catalytic Cu(OTf). Decarboxylative cyclization of 1-methylindole-2- or indole-3-carboxylic acids with substituted propargyl alcohols under Lewis (for 1-methylindole-2-carboxylic acid) or Brønsted (for 1-methylindole-3-carboxylic acid) acid catalysis gives the same 3,4-dihydrocyclopentaindoles, demonstrating 3- to 2-carboxylate migration in the latter case.

Transition-Metal-Free, Brønsted Acid-Mediated Cascade Sequence in the Reaction of Propargyl Alcohols with Sulfonamido-indoles/-indolines: Highly Substituted δ- and α-Carbolines.

Brønsted acid-mediated, transition-metal-free reaction of propargyl alcohols with sulfonamido-indoles/-indolines under mild conditions affords highly substituted δ- or α-carbolines in good to excellent yields. This protocol involves cascade reaction sequences of Friedel-Crafts alkylation/ [1,5]-hydrogen shift/electrocyclization/elimination/ [1,2]-aryl migration followed by aromatization. An unexpected regioselective tosyl group migration from indole 2- to 6-position and arene elimination leading to α-carbolines has also been discovered.