Structure elucidation and biological activities of perylenequinones from an Alternaria species.

The KEAP1-Nrf2/ARE pathway is a pivotal cytoprotective regulator against oxidative stress which plays an important role in the development of many inflammatory diseases and cancer. Activation of the Nrf2 transcription factor by oxidative stress or electrophiles regulates antioxidant response element (ARE)-dependent transcription of antioxidative, detoxifying, and anti-inflammatory proteins. Therefore, modulators of the KEAP1-Nrf2/ARE pathway have received considerable interest as therapeutics to protect against diseases where oxidative stress constitutes the underlying pathophysiology. In a search for fungal secondary metabolites affecting the Nrf2/ARE-dependent expression of a luciferase reporter gene in BEAS-2B cells, three new perylenequinones, compounds 1, 2, and 3, together with altertoxin-I (ATX-I), were isolated from fermentations of an Alternaria species. The structures of the compounds were elucidated by a combination of one- and two-dimensional NMR spectroscopy and mass spectrometry. Compound 1 and ATX-I exhibited strong cytotoxic effects with LC50-values of 3.8 µM and 6.43 µM, respectively, whereas compound 3 showed no cytotoxic effects up to 100 µM on BEAS-2B cells. ATX-I induced ARE-dependent luciferase expression approximately fivefold and compound 1 approximately 2.6-fold at a concentration of 3 µM in transiently transfected BEAS-2B cells. In addition, compound 1 and ATX-I exhibited strong oxidative effects, whereas compound 3 did not show significant oxidative properties. For compound 1 and ATX-I, a strong upregulation of heme oxygenase-1 could be observed on mRNA and protein level in treated BEAS-2B cells. Moreover, compound 3 significantly decreased sod3 mRNA levels after induction of oxidative stress with benzoquinone.

Xylochemical Synthesis and Biological Evaluation of the Orchidaceous Natural Products Isoarundinin I, Bleochrin F, Blestanol K, and Pleionol.

The first total syntheses of the orchid-derived natural products isoarundinin I (1), (±)-bleochrin F ((±)-2), (±)-blestanol K ((±)-3), and (±)-pleionol ((±)-4) from renewable starting materials are reported, along with the evaluation of their biological activities. The total syntheses were based on regioselective aromatic bromination reactions in combination with a key acid-promoted regioselective intramolecular cyclization. The biological results suggest that isoarundinin I (1), (±)-blestanol K ((±)-3), and (±)-pleionol ((±)-4) have the potential to inhibit the growth of both sensitive and multidrug-resistant cancer cells.

Marine Pyrrole Alkaloids.

Nitrogen heterocycles are essential parts of the chemical machinery of life and often reveal intriguing structures. They are not only widespread in terrestrial habitats but can also frequently be found as natural products in the marine environment. This review highlights the important class of marine pyrrole alkaloids, well-known for their diverse biological activities. A broad overview of the marine pyrrole alkaloids with a focus on their isolation, biological activities, chemical synthesis, and derivatization covering the decade from 2010 to 2020 is provided. With relevant structural subclasses categorized, this review shall provide a clear and timely synopsis of this area.

Xylochemical Synthesis and Biological Evaluation of Shancigusin C and Bletistrin G.

The biological activities of shancigusin C (1) and bletistrin G (2), natural products isolated from orchids, are reported along with their first total syntheses. The total synthesis of shancigusin C (1) was conducted by employing the Perkin reaction to forge the central stilbene core, whereas the synthesis of bletistrin G (2) was achieved by the Wittig olefination followed by several regioselective aromatic substitution reactions. Both syntheses were completed by applying only renewable starting materials according to the principles of xylochemistry. The cytotoxic properties of shancigusin C (1) and bletistrin G (2) against tumor cells suggest suitability as a starting point for further structural variation.

Synthesis of Morphinans through Anodic Aryl-Aryl Coupling.

The morphinans are an important class of structurally fascinating and physiologically important natural products as exemplified by the famous opium alkaloids of the morphine family. Although this class of secondary metabolites from the juice of the opium poppy capsule was already used for medicinal purposes thousands of years ago, chemical modifications are still being applied to the core structure today in order to achieve the most specific effect on the various receptor subtypes possible with the fewest possible side effects. The unusual architecture of the morphinan core has also proven to be a highly challenging target for total synthesis. This review highlights electrosynthetic approaches towards natural and semisynthetic morphinan alkaloids. The historical progress in applying anodic aryl-aryl couplings to the construction of the morphinan framework is described in chronological order while particular benefits and challenges concerning the electrochemical transformations are grouped together, including the influence of substitution patterns, protecting groups, and reaction conditions.

One-Pot Oxidative C-H Activation/Aza-Prins-Type Reaction of Tertiary Alkynylamines: A Counter Ion-Induced Iminium Ion-Alkyne Cyclization.

Herein, the design and development of a new one-pot and metal-free oxidative C-H activation/aza-Prins type cyclization of alkynylamines is reported. The scope of this method was demonstrated by the preparation of ten new pyrido[2,1-a]isoquinolines in moderate to high yields (38-92%). Furthermore, a mechanistic proposal for the alkyne aza-Prins cyclization is described based on DFT calculations.