Enantioselective Carbon Isotope Exchange.

The synthesis of isotopically labeled organic molecules is vital for drug and agrochemical discovery and development. Carbon isotope exchange is emerging as a leading method to generate carbon-labeled targets, which are sought over hydrogen-based labels due to their enhanced stability in biological systems. While many bioactive small molecules bear carbon-containing stereocenters, direct enantioselective carbon isotope exchange reactions have not been established.

A practical guide for the preparation of C1-labeled α-amino acids using aldehyde catalysis with isotopically labeled CO.

Isotopically carbon-labeled α-amino acids are valuable synthetic targets that are increasingly needed in pharmacology and medical imaging. Existing preparations rely on early stage introduction of the isotopic label, which leads to prohibitive synthetic costs and time-intensive preparations. Here we describe a protocol for the preparation of C1-labeled α-amino acids using simple aldehyde catalysts in conjunction with [*C]CO (* = 14, 13, 11).

In situ Generated Iridium Nanoparticles as Hydride Donors in Photoredox-Catalyzed Hydrogen Isotope Exchange Reactions with Deuterium and Tritium Gas.

We have studied the photoredox-catalyzed hydrogen isotope exchange (HIE) reaction with deuterium or tritium gas as isotope sources and in situ formed transition metal nanoparticles as hydrogen atom transfer pre-catalysts. By this means we have found synergistic reactivities applying two different HIE mechanisms, namely photoredox-catalyzed and CH-functionalization HIE leading to the synthesis of highly deuterated complex molecules. Finally, we adopted these findings successfully to tritium chemistry.

Hydrogen Isotope Exchange by Homogeneous Iridium Catalysis in Aqueous Buffers with Deuterium or Tritium Gas.

We have studied the highly selective homogeneous iridium-catalyzed hydrogen isotope exchange (HIE) with deuterium or tritium gas as an isotope source in water and buffers. With an improved water-soluble Kerr-type catalyst, we have achieved the first insight into applying HIE reactions in aqueous media with varying pH. Density functional theory (DFT) calculations gave consistent insights in the calculated energies of transition states and coordination complexes, further explaining the observed reactivity and guidance on the scope and limitations for HIE reactions in water.

Chemoenzymatic Total Synthesis of Sorbicatechol Structural Analogues and Evaluation of Their Antiviral Potential.

Sorbicillinoids are fungal polyketides characterized by highly complex and diverse molecular structures, with considerable stereochemical intricacy combined with a high degree of oxygenation. Many sorbicillinoids possess promising biological activities. An interesting member of this natural product family is sorbicatechol A, which is reported to have antiviral activity, particularly against influenza A virus (H1N1).

Chemo-enzymatic Total Synthesis of Oxosorbicillinol, Sorrentanone, Rezishanones B and C, Sorbicatechol A, Bisvertinolone, and (+)-Epoxysorbicillinol.

The sorbicillinoids are a large family of fungal natural products, many of which possess highly challenging molecular architectures. Depending on their individual structures they exhibit strong biological activities ranging from radical scavenging and anti-infective properties to cytotoxicity. Despite the resulting strong biomedical potential of these natural products and the interest of synthetic chemists owing to their fascinating structures, many sorbicillinoids are currently not synthetically accessible, thus hampering in-depth biological characterization and structural diversification.

Stereoselective Total Synthesis of Bisorbicillinoid Natural Products by Enzymatic Oxidative Dearomatization/Dimerization.

Natural products are a virtually inexhaustible source of small molecules with spectacular molecular architectures and biomedical potential. Their structural complexity generates formidable challenges to total synthesis but often also precludes time- and resource-efficient, stereoselective synthetic access. Biosynthetically, nature frequently uses dimerization and oligomerization reactions to produce highly challenging frameworks from simple starting materials.