Fluorinated α‐amino acids are versatile compounds that are used for many purposes in medicinal and biochemistry. However, their synthesis remains a significant hurdle, often requiring multiple steps, multiple protecting groups, and/or the use of highly toxic reagents. These challenges have limited the application of fluorinated α‐amino acids. A convenient, protecting‐group‐free and semi‐continuous process for the synthesis of racemic fluorinated α‐amino acids from fluorinated amines is described. Following a singlet‐oxygen‐driven photooxidative cyanation, an acid‐mediated hydrolysis of the intermediate α‐amino nitrile yields the desired α‐amino acid. Aliphatic, benzylic, and homobenzylic residues with different fluorination degrees are tolerated, providing good overall yields (50–67 %). This semi‐continuous process is particularly advantageous for an aliphatic amine, the intermediate α‐amino nitrile of which decomposes upon isolation.

Most successful reactions carried out under continuous flow conditions mix homogeneous solutions yielding homogeneous products. Using solids is avoided to prevent pump and reactor clogging; even though solid reagents may often be the best choice for a given transformation. Here we demonstrate that by pumping aldehydes, ketones, or in situ formed imines through a specially formulated NaBH4 column results in efficient reductions. The column design and performance characteristics, along with substrate scope, are discussed.

Hydantoins are an important class of heterocycles with applications in pharmacy, agriculture, and as intermediates in organic synthesis. Traditional synthetic procedures to access hydantoins are target oriented with multiple synthetic steps and often use reagents that are not commercially available or sustainable. Herein, an efficient process is described for accessing hydantoins starting from commercially available amines using consecutive gas-liquid transformations (oxygen, carbon dioxide). This semi-continuous process produced ten benzylic/aliphatic hydantoins in good overall yields (52-84 %).

Compressed tablets containing a mixture of a photocatalyst, a nickel catalyst, an inorganic base, and an inert excipient are employed as a fast, safe, and user-friendly chemical delivery system for two different metallophotoredox-catalyzed reactions. This delivery method simplifies the preparation of compound libraries using photoredox chemistry in a parallel setting. The reagent tablets were successfully applied to late-stage functionalization of drug-like intermediates. These tablets can be prepared with various reagents and catalysts in different sizes and be stored on the bench thanks to blister packaging.

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Our aim was to study the impact of two proline chimeras, containing a glutamic acid side chain in cis- or trans-configuration, on secondary structure formation. We further investigated to what extent the configuration of the side chain contributes to the overall peptide conformation. We used a 10 residue peptide (IYSNPDGTWT) that forms a β-hairpin in water. The turn-forming proline was substituted with either a cis- or trans-proline-glutamic acid chimera, resulting in the peptides IYSNPcis -E DGTWT (P1_Pcis-E) and IYSNP(trans-E)DGTWT (P1_Ptrans-E). We studied the conformation of the modified peptides by circular dichroism (CD) and NMR-spectroscopy, and SEC/static light scattering (SLS) analysis. NMR analysis reveals that the modified peptides maintain the β-hairpin conformation in aqueous solution. At 5 °C and pH 4.3, the peptide (P1_Pcis-E) was found to adopt two coexisting β-hairpin conformations (2:2 β-hairpin, and 3:5 β-hairpin). In contrast to that, the peptide (P1_Ptrans-E) adopts a 2:2 β-hairpin that exists in equilibrium with a 4:4 β-hairpin conformation. The adoption of ordered β-hairpin structures for both modified peptides could be confirmed by CD spectroscopy, while SEC/SLS analysis showed a monomeric oligomerization state for all three investigated peptides. With the combination of several NMR methods, we were able to elucidate that even small alterations in the side chain conformation of the proline-glutamate chimera (cis or trans) can significantly influence the conformation of the adopted β-hairpin.

Flow Synthesis of Fluorinated -Amino Acids. -A semi-continuous process involving photooxidative cyanation of fluorinated amines and subsequent hydrolysis of the resulting nitriles allows the synthesis of fluorinated -amino acids. -(VUKELIC, S.; USHAKOV, D. B.; GILMORE, K.; KOKSCH*, B.; SEEBERGER, P. H.; Eur. J. Org. Chem. 2015, 14, 3036-3039, http://dx.doi.org/10.1002/ejoc.201500300 ; Inst. Chem.

Several new adamantyl and homoadamantyl-substituted [Formula: see text]-hydroxybutyric acids, 2-[2-(1-adamantyl)ethyl]-3-hydroxybutyric acid (2), 2-(3-homoadamantyl)-3-hydroxybutyric acid (3), and 2-(1-homoadamantyl)-3-hydroxybutyric acid (4), analogues of the 2-(1-adamantyl)-3-hydroxybutyric acid (1), have been prepared as mixtures of diastereoisomers using selective reduction of corresponding [Formula: see text]-keto esters or aldol condensation of the corresponding carboxylic acid and acetaldehyde. The rearrangement of adamantylmethyl and 3-homoadamantyl groups provided entry to both 3-homoadamantyl and 1-homoadamantyl-substituted hydroxy acids 3 and 4, respectively. The relative configurations of diastereoisomers 3 and 4 have been determined by NMR spectroscopy comparing the values of coupling constants. Adamantyl-substituted [Formula: see text]-hydroxybutyric acid 2 has also been prepared in enantiomerically pure form by Evan's asymmetric synthesis and the absolute configuration has been determined by X-ray crystallography. Contrary to the long-chain acid 2, the attempt to prepare short-chain hydroxy acids 1 and 4 by the same method failed indicating pronounced sensitivity of the used method to the vicinity of the bulky cage group.