A Cyclobutanol Ring-Expansion Approach to Oxygenated Carbazoles: Total Synthesis of Glycoborine, Carbazomycin A and Carbazomycin B

Abstract

The transition-metal-free total syntheses of the oxygenated carbazole natural products glycoborine, carbazomycin A and carbazomycin B are reported. The key step involves an NBS-mediated cyclobutanol ring expansion to 4-tetralones for the preparation of the tricyclic carbazole core.

Deprotonative Generation and Trapping of Haloaryllithium in a Batch Reactor

“…To demonstrate the synthetic utility of this method, we conducted the practical total synthesis of antibiotic carbazomycin A ( 9 ), which was originally isolated from Streptomyces Strain H 1051-MY 10 by Nakamura and co-workers in 1980 (Scheme ). The biological activity of carbazomycin A and its unique structure, bearing the fully substituted benzene moiety, have attracted the attention of synthetic chemists, leading to eleven total syntheses over the recent decades Our synthesis commenced with C–H arylation of symmetrical chloroarene 10 using the established conditions. Thus, the combination of LiTMP and ZnCl 2 ·TMEDA provided the organozinc species 11 without aryne formation, which underwent Negishi coupling with 2-iodoaniline to give 2-aminobiphenyl 12 in 65% yield.…”

Trends in carbazole synthesis – an update (2013–2023)

“…There is a significant body of work on the conversion of tetrahydrocarbazoles and tetrahydrocarbazol-1-ones to carbazoles. [122][123][124][125][126][127][128][129][130][131][132] Over several publications, Lokhande developed iodine-and copper-mediated oxidations of tetrahydrocarbazoles. [133][134][135] Iodine was used to produce carbazoles, such as glycozoline and a, or 3-iodocarbazoles by varying the stoichiometry.…”

“…Tetrahydrocarbazol-1-ones readily form indolocarbazoles or oxygenated carbazoles. [139][140][141] Kotha produced the indolocarbazoles by treating tetrahydrocarbazol-1-ones 65 with dimethyl urea (DMU) and tartaric acid. 139 This process formed core of tjupanazoles 142 in one-step from the corresponding ketone, as well as the core structures of asteropusazole and racemosin B (Scheme 19).…”

“…In 2023, Parsons reported the synthesis of glycoborine (a 5-oxygenated tricyclic natural carbazole isolated from the root of Glycosmis arborea) 143 and carbazomycin A & B by oxidising late-stage tetrahydrocarbazol-4-ones 68 with iodine or N-bromosuccinimide (NBS) respectively. 140 Notably, this work uses an NBS-mediated cyclobutanol ring expansion strategy to form the tetrahydrocarbazolones, [144][145][146] rather than a Fischer indole synthesis employed by the above research groups (Scheme 20). The N-bromosuccinimide oxidation used by Parsons was first reported by Nishida in their ytterbium-catalysed Diels-Alder synthesis of Carbazomycin A and B.…”

Iodine-promoted synthesis of CF3-substituted dihydroimidazobenzimidazole and CF3-dihydroimidazoindole via C–N bond formation

“…Treatment of 4a with KOH in EtOH under reflux for 2 h afforded the corresponding free N-H product 8a in 69% isolated yield (Scheme 3). 8…”