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Nitrogen heterocycles (azacycles) are common structural motifs in numerous pharmaceuticals, agrochemicals, and natural products. Many powerful methods have been developed and continue to be advanced for the selective installation and modification of nitrogen heterocycles through C-H functionalization and C-C cleavage approaches, revealing new strategies for the synthesis of targets containing these structural entities. Here, we report the first total syntheses of the lycodine-type Lycopodium alkaloids casuarinine H, lycoplatyrine B, lycoplatyrine A, and lycopladine F as well as the total synthesis of 8,15-dihydrohuperzine A through bioinspired late-stage diversification of a readily accessible common precursor, N-desmethyl-β-obscurine. Key steps in the syntheses include oxidative C-C bond cleavage of a piperidine ring in the core structure of the obscurine intermediate and site-selective C-H borylation of a pyridine nucleus to enable cross-coupling reactions.

Die Verwendung von CO2 als Kohlenstoffquelle in der Synthese organischer Verbindungen entspricht den aktuellen Bemühungen für eine nachhaltigere Produktion von Chemikalien. Wir beschreiben hier die enzymkatalysierte para-Carboxylierung von Catecholen durch eine 3,4-Dihydroxybenzoesäure-Decarboxylase (AroY) aus der UbiD-Enzymfamilie. Die Kristallstrukturen und experimentelle Daten zeigen, dass dieses Enzym ein erst kürzlich entdecktes prenyliertes Flavin als Cofaktor benötigt (prFMN) und oxidative Prozesse zur Bildung der katalytisch aktiven prFMNiminium-Spezies führen. Diese Studie beschreibt die In-vitro-Rekonstitution und Aktivierung dieser prFMN-abhängigen Enzyme, welche die direkte Carboxylierung von aromatischen Catecholen unter milden Bedingungen katalysieren. Ein Reaktionsmechanismus für den reversiblen Carboxylierungsprozess über ein Intermediat mit einfach kovalent gebundener Chinoidform des Substrats wird vorgeschlagen, der sich von dem 1,3-Cycloadditionsmechanismus in verwandten Enzymen unterscheidet. [ABSTRACT FROM AUTHOR]

The (+)- as well as the (−)-enantiomer of the pyrrolizidine alkaloid xenovenine were prepared within five steps with 17 and 30% overall yields, respectively, in optically pure form, >99% ee as well as >99% de. In the asymmetric key step a transaminase performed a regio- and stereoselective monoamination of a triketone. By employing two enantiocomplementary transaminases from Arthrobacter sp. both enantiomers were accessible. The triketone was readily prepared via two steps starting from commercially available, achiral 2-( n-heptyl)furan. In the final catalytic hydrogenation step, the newly introduced chiral centre directed hydrogen addition to form preferentially the desired (5 Z,8 E)-diastereomer. The regio- and stereoselective amination of a single ketone moiety out of three allowed the performance of the shortest and highest yielding total synthesis of the bicyclic showcase pyrrolizidine alkaloid without the need for protecting strategies. [ABSTRACT FROM AUTHOR]

The front cover picture, designed by Verena A. Resch and Stefan Payer, illustrates creating three stereocenters in two steps: the regio ‐ and stereoselective mono ‐ amination of a prochiral triketone followed by chemical reduction gave access to xenovenine, the venom of the ant species Solenopsis tennesseensis. Each enantiomer can be accessed by switching from an (S) ‐ to an (R) ‐ selective biocatalyst in the asymmetric key step of the sequence. Details can be found in the Full Paper on pages 444 – 451 (S. E. Payer, J. H. Schrittwieser, B. Grischek, R. C. Simon, W. Kroutil, Adv. Synth. Catal.­ 2016, 358, 444 – 451; DOI: 10.1002/adsc.201500781). The authors acknowledge supported by the University of Graz for the printing of the cover picture. [ABSTRACT FROM AUTHOR]

Broad substrate tolerance and excellent regioselectivity, as well as independence from sensitive cofactors have established benzoic acid decarboxylases from microbial sources as efficient biocatalysts. Robustness under process conditions makes them particularly attractive for preparative-scale applications. The divalent metal-dependent enzymes are capable of catalyzing the reversible non-oxidative (de)carboxylation of a variety of electron-rich (hetero)aromatic substrates analogously to the chemical Kolbe-Schmitt reaction. Elemental mass spectrometry supported by crystal structure elucidation and quantum chemical calculations verified the presence of a catalytically relevant Mg 2+ complexed in the active site of 2,3-dihydroxybenoic acid decarboxylase from Aspergillus oryzae (2,3-DHBD_Ao). This unique example with respect to the nature of the metal is in contrast to mechanistically related decarboxylases, which generally have Zn 2+ or Mn 2+ as the catalytically active metal., (© 2020 The Authors. ChemBioChem published by Wiley-VCH GmbH.)