Stereocontrol in Nucleophilic Substitution Reactions at Silicon: The Role of Permutation in Generating Silicon-Centered Chirality

Intramolecular isomerization in pentacoordinate compounds can play an essential role for the adjustment of defined stereochemical information. Here, we present a conclusive mechanism of a stereocontrolled reaction on chiral dimethoxysilanes that opens new aspects in understanding the origin of creating silicon-centered chirality during a nucleophilic substitution process. By combining experimental, structural, and quantum chemical methods, we were able to disclose an interconversion process, based on consecutive Berry-type motions, as the most plausible mechanism for describing the stereochemical outcome in suchlike substitution reactions

Organocatalytic, Oxidative, Intermolecular Amination and Hydrazination of Simple Arenes at Ambient Temperature

New atom-economical, environmental friendly, direct oxidative intermolecular processes of amination and hydrazination of nonprefunctionalized arenes were developed. The products were formed in a good regioselective manner under organocatalytic conditions at ambient temperature

Formation of Specific Configurations at Stereogenic Nitrogen Centers upon Their Coordination to Zinc and Mercury

The coordination of (<i>R</i>,<i>R</i>)-tetramethylcyclohexane-1,2-diamine derivatives with stereogenic nitrogen centers to zinc and mercury halides is investigated. It is shown that the resulting complexes display one specific configuration at the stereogenic nitrogen centers. This fact is unusual due to the fast inversion of nitrogen centers but highly desirable as the stereoinformation of the ligands is brought closer to the metal centers of the potential catalysts. A combination of NMR studies and quantum chemical calculations gives insight into the selective formation of one specific configuration at the stereogenic nitrogen centers of the zinc complexes

Formation of Specific Configurations at Stereogenic Nitrogen Centers upon Their Coordination to Zinc and Mercury

The coordination of (<i>R</i>,<i>R</i>)-tetramethylcyclohexane-1,2-diamine derivatives with stereogenic nitrogen centers to zinc and mercury halides is investigated. It is shown that the resulting complexes display one specific configuration at the stereogenic nitrogen centers. This fact is unusual due to the fast inversion of nitrogen centers but highly desirable as the stereoinformation of the ligands is brought closer to the metal centers of the potential catalysts. A combination of NMR studies and quantum chemical calculations gives insight into the selective formation of one specific configuration at the stereogenic nitrogen centers of the zinc complexes

Synthesis of an Iridoid-Inspired Compound Collection and Discovery of Autophagy Inhibitors

Iridoids comprise a large group of monoterpenoid natural products displaying a diverse array of biological activities ranging from neurotrophic to anti-inflammatory and anti-tumorigenic properties. Therefore, the development of concise synthesis routes to compound collections inspired by the structural features of these natural products is of particular relevance for chemical biology and medicinal chemistry. Herein we describe a samarium diiodide-mediated synthesis of a small, focused iridoid-inspired compound collection. Characterization of these iridoid analogues in biological assays revealed novel small-molecule inhibitors of autophagy

Asymmetric Roadmap to Diverse Polycyclic Benzopyrans via Phosphine-Catalyzed Enantioselective [4 + 2]-Annulation Reaction

The catalytic addition of the amino acid derived bifunctional <i>N</i>-acylamino­phosphine to an α-substituted allene ester generated a zwitterionic dipole that engaged the vinylogous ester function of 3-cyano-chromones in a [4 + 2] annulation reaction to deliver tetrahydroxanthones embodying three consecutive chiral centers in high yields and with excellent enantioselectivities. The established asymmetric synthesis further paves the way to two different classes of complex, sp³-rich tetracyclic benzopyrans via efficient cascade reactions

Synthesis of an Iridoid-Inspired Compound Collection and Discovery of Autophagy Inhibitors

Iridoids comprise a large group of monoterpenoid natural products displaying a diverse array of biological activities ranging from neurotrophic to anti-inflammatory and anti-tumorigenic properties. Therefore, the development of concise synthesis routes to compound collections inspired by the structural features of these natural products is of particular relevance for chemical biology and medicinal chemistry. Herein we describe a samarium diiodide-mediated synthesis of a small, focused iridoid-inspired compound collection. Characterization of these iridoid analogues in biological assays revealed novel small-molecule inhibitors of autophagy

Synthesis of an Iridoid-Inspired Compound Collection and Discovery of Autophagy Inhibitors

Iridoids comprise a large group of monoterpenoid natural products displaying a diverse array of biological activities ranging from neurotrophic to anti-inflammatory and anti-tumorigenic properties. Therefore, the development of concise synthesis routes to compound collections inspired by the structural features of these natural products is of particular relevance for chemical biology and medicinal chemistry. Herein we describe a samarium diiodide-mediated synthesis of a small, focused iridoid-inspired compound collection. Characterization of these iridoid analogues in biological assays revealed novel small-molecule inhibitors of autophagy

A Formal, One-Pot β‑Chlorination of Primary Alcohols and Its Utilization in the Transformation of Terpene Feedstock and the Synthesis of a <i>C</i>₂‑Symmetrical Terminal Bis-Epoxide

A one-pot transformation of alkan-1-ols into 2-chloroalkan-1-ols is described. As a practical application, terpene-derived primary alcohols were converted into semiochemicals such as olfactory lactones (aerangis lactone, whisky lactone, and cognac lactone) and pheromones (cruentol and ferrugineol). Using heptane-1,7-diol as a bifunctional substrate, the corresponding bis-epoxide was synthesized by bidirectional synthesis in good yield and high enantioselectivity

Epigenetic Modulation of Endophytic Eupenicillium sp. LG41 by a Histone Deacetylase Inhibitor for Production of Decalin-Containing Compounds

An endophytic fungus, Eupenicillium sp. LG41, isolated from the Chinese medicinal plant Xanthium sibiricum, was subjected to epigenetic modulation using an NAD⁺-dependent histone deacetylase (HDAC) inhibitor, nicotinamide. Epigenetic stimulation of the endophyte led to enhanced production of two new decalin-containing compounds, eupenicinicols C and D (<b>3</b> and <b>4</b>), along with two biosynthetically related known compounds, eujavanicol A (<b>1</b>) and eupenicinicol A (<b>2</b>). The structures and stereochemistry of the new compounds were elucidated by extensive spectroscopic analysis using LC-HRMS, NMR, optical rotation, and ECD calculations, as well as single-crystal X-ray diffraction. Compounds <b>3</b> and <b>4</b> exist in chemical equilibrium with two and three <i>cis</i>/<i>trans</i> isomers, respectively, as revealed by LC-MS analysis. Compound <b>4</b> was active against Staphylococcus aureus with an MIC of 0.1 μg/mL and demonstrated marked cytotoxicity against the human acute monocytic leukemia cell line (THP-1). We have shown that the HDAC inhibitor, nicotinamide, enhanced the production of compounds <b>3</b> and <b>4</b> by endophytic Eupenicillium sp. LG41, facilitating their isolation, structure elucidation, and evaluation of their biological activities