Modern flow chemistry – prospect and advantage

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Biogenetic space-guided synthesis of rearranged terpenoids

Natural product chemistry is constantly challenged by newly discovered, complex molecules. Elements of complexity arise from unprecedented frameworks, with a large amount of densely packed stereogenic centres and different functional groups along with a generally high oxidation state. As a prime example, rearranged triterpenoids possess all these elements. For their total synthesis, a limit of what is considered sensible in terms of steps and yield is frequently reached. As an alternative, semisynthetic approaches have gained a great amount of attention in recent years. In this featured article, we present our and others' contributions towards the development of efficient and economic syntheses of complex terpenoid natural products and elaborate on the underlying rationale of biogenetic space-guided synthetic analysis

Scalable Synthesis of Benzotriazoles via [3+2] Cycloaddition of Azides and Arynes in Flow

A method for the metal-free synthesis of benzotriazoles in flow is reported. Using azides and in situ generated arynes, benzotriazoles are formed in a [3+2] cycloaddition within minutes. Employing different substitution patterns of the azide and aryne coupling partners, a modular access to benzotriazoles is provided. Thermal strain of hazardous azides and accumulation of reactive intermediates is minimized by short reaction times in flow, improving the safety profile of the process. The scalability of the reaction is demonstrated

Discoveries and challenges en route to swinhoeisterol A

In this work, a full account of the authors’ synthetic studies is reported that culminated in the first synthesis of 13(14→8),14(8→7)diabeo‐steroid swinhoeisterol A as well as the related dankasterones A and B, 13(14→8)abeo‐steroids, and periconiastone A, a 13(14→8)abeo‐4,14‐cyclo‐steroid. Experiments are described in detail that provided further insight into the mechanism of the switchable radical framework reconstruction approach. By discussing failed strategies and tactics towards swinhoeisterol A, the successful route that also allowed an access to structurally closely related analogues, such as Δ22‐24‐epi‐swinhoeisterol A, is eventually presented

Photochemical degradation of trypan blue

Purpose To investigate the photochemical degradation of trypan blue (TB) and to identify decomposition products. Methods Defined solution samples of TB and a mixture with lutein/zeaxanthin were exposed to blue light. Thermal degradation processes were ruled out using controls not subjected to irradiation. All samples were analyzed using optical microscopy, UVNis spectroscopy, matrix assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry and nuclear magnetic resonance (NMR) spectrometry. Degradation kinetics were determined based on changes in absorbance; intermediates were identified by analyzing mass differences of characteristic fragment ion peaks within the fragmentation patterns, and assignments were verified by NMR. Results TB demonstrated a photochemical degradation, which can be triggered by lutein/zeaxanthin. Intermediates vary depending on the presence of lutein/zeaxanthin. The self-sensitized photodegradation of TB occurs under generation of dimethyl sulfate and presumed formation of phenol. In contrast, within the presence of lutein/zeaxanthin the decomposition of TB indicates the formation of methoxyamine and sulfonyl arin. Thermal degradation processes were not observed. Conclusions TB demonstrated a photodegradation that may be triggered by lutein/zeaxanthin and results in the formation of cytotoxic decomposition products. Our findings contribute to understand degradation mechanisms of TB and may elucidate previous clinical and experimental observations of cellular toxicity after TB application

Chemical Emulation of the Biosynthetic Route to Anthrasteroids: Synthesis of Asperfloketal A

The anthrasteroid rearrangement has been discussed for the formation of the eponymous substance class since its discovery. We here report its chemical emulation from a plausible biogenetic precursor and show how it accounts for the formation of asperflo­ketals A and B through a mechanistic bifurcation event. As a result, these natural products arise from double Wagner–Meerwein rearrangements and, thus, are 1(10→5),​1(5→6)​- and 1(10→5),​4(5→6)​diabeo-14,15-seco­steroids, respectively. To establish an efficient route to a bioinspired precursor, we devised a sequence of orchestrated oxidative activation and rearrangement from ergosterol

A Modular, Argon-Driven Flow Platform for Natural Product Synthesis and Late-Stage Transformations

A modular flow platform for the synthesis of natural products and their analogs was designed. To access different reaction setups with a maximum of flexibility, interchangeable 3D-printed components serve as backbone. By switching from conventional liquid- to gas-driven flow, reagent and solvent waste is minimized which translates into an advantageous sustainability and economy profile. To enable inert conditions, practical “Schlenk-in-flow” techniques for the safe handling of oxygen- and moisture sensitive reagents were developed. Adopting these techniques, reproducible transformations in natural product synthesis were achieved

Five‐Step Synthesis of Yaequinolones J1 and J2

A concise synthesis of yaequinolones J1 and J2 is reported. The route is based on the aryne insertion into the σ- C–N-bond of an unsymmetric imide followed by a diastereoselective aldol cyclization of the resulting N-acylated aminobenzophenone. The chromene motif is generated in the first step by an organocatalytic tandem Knoevenagel-electrocyclization of citral and 2-bromoresorcinol. The approach adheres to the ideality-principle, using almost exclusively strategic bond-formingreactions