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A formal total synthesis of the natural macrolide antibiotic tiacumicin B is described featuring successive and selective glycosylations of tiacumicinone. The challenging β‐facial selectivity of these key glycosylation steps was achieved by using noviosyl or rhamnosyl donors equipped with a phenyl sulfoxide leaving group and a 3‐O‐picoloyl group ensuring an efficient remote stereodirecting effect. Compared with our former total synthesis, this strategy enables us to save steps and gain access to new analogs. This was demonstrated by the replacement of the rhamnosidic moiety by a d‐mannose derivative. [ABSTRACT FROM AUTHOR]

Camellimidazoles A–C were recently reported as natural substances in Keemun black tea. Although a "biosynthetic" route to these intriguing imidazole dimers was proposed from caffeine by the authors in this seminal report, we envisioned that a artefactual scenario, consisting of alkaline hydrolysis of caffeine and spontaneous cascade reactions with a methylene donor such as formaldehyde or methylene chloride, could also have led to their formation. To capture the diversity of molecules obtained under these conditions (i.e. alkaline treatment of caffeine/formaldehyde), an in silico MetWork‐based pipeline was implemented, highlighting the sought‐after camellimidazoles B and C. A wealth of further compounds were also tagged, notably comprising the herein newly described and unnatural camellimidazoles D–F that were subsequently confirmed as anticipated in silico upon extensive spectroscopic analyses. Likewise, camellimidazoles B and C could also be obtained using methylene chloride as an alternative methylene donor which may also have occurred in the initial phytochemical pipeline that implied this solvent. The current investigation emphasizes the fitness of MetWork tagging to extend the logic of in silico anticipation of metabolic pathways to organic chemistry reactions. [ABSTRACT FROM AUTHOR]

Reported is the enantioselective total syntheses of mavacuran alkaloids, (+)‐taberdivarine H, (+)‐16‐hydroxymethyl‐pleiocarpamine, and (+)‐16‐epi‐pleiocarpamine, and their postulated biosynthetic precursor 16‐formyl‐pleiocarpamine. This family of monoterpene indole alkaloids is a target of choice since some of its members are subunits of intricate bisindole alkaloids such as bipleiophylline. Inspired by the biosynthetic hypothesis, an oxidative coupling approach from the geissoschizine framework to form the N1−C16 bond was explored. Quaternization of the aliphatic nitrogen center was key to achieving the oxidative coupling induced by KHMDS/I2 as it masks the nucleophilicity of the aliphatic nitrogen center and locks in the required cis conformation. [ABSTRACT FROM AUTHOR]

A methodological study towards the total synthesis of marmycin A/B is described exploiting a commercial anthraquinone molecule as model compound. The challenging synthetic pathway uncovers a copper-catalysed Ullmann cross-coupling to attach the sugar backbone by means of C–N bond formation and, finally, an intramolecular Friedel–Crafts C–C glycosylation to successfully afford the core structure of marmycin A. This methodology has been successfully applied to the genuine anthraquinone moiety leading to the natural product and simpler structural analogues. [ABSTRACT FROM AUTHOR]