The development of potent adjuvants is an important step for improving the performance of subunit vaccines. CD1d agonists, such as the prototypical α‐galactosyl ceramide (α‐GalCer), are of special interest due to their ability to activate iNKT cells and trigger rapid dendritic cell maturation and B‐cell activation. Herein, we introduce a novel derivatization hotspot at the α‐GalCer skeleton, namely the N‐substituent at the amide bond. The multicomponent diversification of this previously unexplored glycolipid chemotype space permitted the introduction of a variety of extra functionalities that can either potentiate the adjuvant properties or serve as handles for further conjugation to antigens toward the development of self‐adjuvanting vaccines. This strategy led to the discovery of compounds eliciting enhanced antigen‐specific T cell stimulation and a higher antibody response when delivered by either the parenteral or the mucosal route, as compared to a known potent CD1d agonist. Notably, various functionalized α‐GalCer analogues showed a more potent adjuvant effect after intranasal immunization than a PEGylated α‐GalCer analogue previously optimized for this purpose. Ultimately, this work could open multiple avenues of opportunity for the use of mucosal vaccines against microbial infections.

Fungal unspecific peroxygenases (UPOs) have gained substantial attention for their versatile oxyfunctionalization chemistry paired with impressive catalytic capabilities. A major drawback, however, remains their sensitivity towards their co‐substrate hydrogen peroxide, necessitating the use of smart in situ hydrogen peroxide generation methods to enable efficient catalysis setups. Herein, we introduce flavin‐containing protein photosensitizers as a new general tool for light‐controlled in situ hydrogen peroxide production. By genetically fusing flavin binding fluorescent proteins and UPOs, we have created two virtually self‐sufficient photo‐enzymes (PhotUPO). Subsequent testing of a versatile substrate panel with the two divergent PhotUPOs revealed two stereoselective conversions. The catalytic performance of the fusion protein was optimized through enzyme and substrate loading variation, enabling up to 24300 turnover numbers (TONs) for the sulfoxidation of methyl phenyl sulfide. The PhotUPO concept was upscaled to a 100 mg substrate preparative scale, enabling the extraction of enantiomerically pure alcohol products.Graphical Abstract Unspecific peroxygenases (UPOs) have recently gained attraction as versatile oxyfunctionalization catalysts. One shortcoming, however, is their susceptibility towards the co-substrate hydrogen peroxide. As a solution, the concept of light-dependent UPO biocatalysis with genetically encoded flavin-containing photosensitizer proteins for in situ hydrogen peroxide production is introduced.

Research data management (RDM) is needed to assist experimental advances and data collection in the chemical sciences. Many funders require RDM because experiments are often paid for by taxpayers and the resulting data should be deposited sustainably for posterity. However, paper notebooks are still common in laboratories and research data is often stored in proprietary and/or dead-end file formats without experimental context. Data must mature beyond a mere supplement to a research paper. Electronic lab note-books (ELN) and laboratory information managementsystems (LIMS) allow researchers to manage data better and they simplify research and publication. Thus, an agreement is needed on minimum information standards for data handling to support structured approaches to data reporting. As digitalization becomes part of curricular teaching, future generations of digital native chemists will embrace RDM and ELN as an organic part of their research.

In contrast to the myriad of methods available to produce α‐helices and antiparallel β‐sheets in synthetic peptides, just a few are known for the construction of stable, non‐cyclic parallel β‐sheets. Herein, we report an efficient on‐resin approach for the assembly of parallel β‐sheet peptides in which the N‐alkylated turn moiety enhances the stability and gives access to a variety of functionalizations without modifying the parallel strands. The key synthetic step of this strategy is the multicomponent construction of an N‐alkylated turn using the Ugi reaction on varied isocyano‐resins. This four‐component process assembles the orthogonally protected turn fragment and incorporates handles serving for labeling/conjugation purposes or for reducing peptide aggregation. NMR and circular dichroism analyses confirm the better‐structured and more stable parallel β‐sheets in the N‐alkylated peptides compared to the non‐functionalized variants.

For the first time, the Petasis (borono‐Mannich) reaction is employed for the multicomponent labeling and stapling of peptides. The report includes the solid‐phase derivatization of peptides at the N‐terminus, Lys, and Nϵ‐MeLys side‐chains by an on‐resin Petasis reaction with variation of the carbonyl and boronic acid components. Peptides were simultaneously functionalized with aryl/vinyl substituents bearing fluorescent/affinity tags and oxo components such as dihydroxyacetone, glyceraldehyde, glyoxylic acid, and aldoses, thus encompassing a powerful complexity‐generating approach without changing the charge of the peptides. The multicomponent stapling was conducted in solution by linking Nϵ‐MeLys or Orn side‐chains, positioned at i, i+7 and i, i+4, with aryl tethers, while hydroxy carbonyl moieties were introduced as exocyclic fragments. The good efficiency and diversity oriented character of these methods show prospects for peptide drug discovery and chemical biology.

The functionalization of C−H bonds with non‐precious metal catalysts is an important research area for the development of efficient and sustainable processes. Herein, we describe the development of iron porphyrin catalyzed reactions of diazoacetonitrile with N‐heterocycles yielding important precursors of tryptamines, along with experimental mechanistic studies and proof‐of‐concept studies of an enzymatic process with YfeX enzyme. By using readily available FeTPPCl, we achieved the highly efficient C−H functionalization of indole and indazole heterocycles. These transformations feature mild reaction conditions, excellent yields with broad functional group tolerance, can be conducted on gram scale, and thus provide a unique streamlined access to tryptamines.

Amino acids (AAs), important constituents of natural moisturizing factors (NMFs) of the skin are decreased in diseased conditions such as psoriasis and atopic dermatitis. No study so far investigated the uptake of AAs into isolated corneocytes (COR). The present study was performed using 19 AAs, including taurine (TAU), to measure their amount diffused into the COR and binding of these AAs to keratin. Incubation of alanine, aspartic acid, asparagine, glutamine, glutamic acid, histidine, proline, serine and TAU with the isolated COR showed uptake after 24 h of 51.6, 95.4, 98.6, 94.1, 95.6, 90.1, 94.6, 72.9 and 57.8 %, respectively, into the COR but no binding with keratin. Uptake of TAU was validated by time dependent in-vitro diffusion models 'without COR and 'with COR'. The time dependent curve fitting showed that in in-vitro diffusion model 'without COR' there was no change in the total concentration of TAU until 72 hours, while in diffusion model 'with COR' the total conc. decreased to 37.8 % after 72 hours. The Pearson's correlation coefficient 'r' between the conc. curves of both in-vitro diffusion models was -0.54 that was an evidence of significant amount of TAU uptake by the COR. AAs as part of the NMFs have a great potential to be diffused into the COR. This property of the AAs can be employed in further dermatological research on diseased or aged skin conditions with NMFs deficiency.

An important development in the field of macrocyclization strategies towards molecular cages is described. The approach comprises the utilization of a double Ugi four‐component macrocyclization for the assembly of macromulticycles with up to four different tethers, that is, hybrid cages. The innovation of this method rests on setting up the macromulticycle connectivities not through the tethers but through the bridgeheads, which in this case involve N‐substituted amino acids. Both dilution and metal‐template‐driven macrocyclization conditions were implemented with success, enabling the one‐pot formation of cryptands and cages including steroidal, polyether, heterocyclic, peptidic, and aryl tethers. This method demonstrates substantial complexity‐generating character and is suitable for applications in molecular recognition and catalysis.

Hydnora abyssinica A.Br. (Hydnoraceae), a holoparasitic herb, is for the first time recorded for Abyan governorate of South Yemen. Flowers of this species were studied for their ethnobotanical, biological and chemical properties for the first time. In South Yemen, they are traditionally used as wild food and to cure stomach diseases, gastric ulcer and cancer. Phytochemical analysis of the extracts showed the presence of terpenes, tannins, phenols, and flavonoids. The volatile components of the air-dried powdered flowers were identified using a static headspace GC/MS analysis as acetic acid, ethyl acetate, sabinene, α-terpinene, (+)-D-limonene and γ-terpinene. These volatile compounds that characterize the odor and taste of the flowers were detected for the first time in a species of the family Hydnoraceae. The flowers were extracted by n-hexane, dichlormethane, ethyl acetate, ethanol, methanol and water. With exception of the water extract all extracts demonstrated activities against Gram-positive bacteria as well as remarkable radical scavenging activities in DPPH assay. Ethyl acetate, methanol and water extracts exhibited good antifungal activities. The cytotoxic activity of the extracts against FL cells, measured in neutral red assay, was only weak (IC50 > 500 μg /mL). The results justify the traditional use of the flowers of Hydnora abyssinica in South Yemen.

In an endeavor to provide an efficient route to natural product hybrids, described herein is an efficient, highly stereoselective, one‐pot process comprising an organocatalytic conjugate addition of 1,3‐dicarbonyls to α,β‐unsaturated aldehydes followed by an intramolecular isocyanide‐based multicomponent reaction. This approach enables the rapid assembly of complex natural product hybrids including up to four different molecular fragments, such as hydroquinolinone, chromene, piperidine, peptide, lipid, and glycoside moieties. The strategy combines the stereocontrol of organocatalysis with the diversity‐generating character of multicomponent reactions, thus leading to structurally unique peptidomimetics integrating heterocyclic, lipidic, and sugar moieties.