The Evaluation of l-Tryptophan Derivatives as Inhibitors of the l-Type Amino Acid Transporter LAT1 (SLC7A5).

A series of derivatives of the substrate amino acid l-tryptophan have been investigated for inhibition of the L-type amino acid transporter LAT1 (SLC7A5), which is an emerging target in anticancer drug discovery. Of the four isomeric 4-, 5-, 6-, or 7-benzyloxy-l-tryptophans, the 5-substituted derivative was the most potent, with an IC of 19 μM for inhibition of [ H]-l-leucine uptake into HT-29 human colon carcinoma cells. The replacement of the carboxy group in 5-benzyloxy-l-tryptophan by a bioisosteric tetrazole moiety led to a complete loss in potency.

Continuous Monitoring of Shelf Lives of Materials by Application of Data Loggers with Implemented Kinetic Parameters.

The evaluation of the shelf life of, for example, food, pharmaceutical materials, polymers, and energetic materials at room or daily climate fluctuation temperatures requires kinetic analysis in temperature ranges which are as similar as possible to those at which the products will be stored or transported in. A comparison of the results of the evaluation of the shelf life of a propellant and a vaccine calculated by advanced kinetics and simplified 0th and 1st order kinetic models is presented. The obtained simulations show that the application of simplified kinetics or the commonly used mean kinetic temperature approach may result in an imprecise estimation of the shelf life.

Total Synthesis of Pentacyclic (-)-Ambiguine P Using Sequential Indole Functionalizations.

The first synthesis of a pentacyclic ambiguine (ambiguine P) is reported. The synthesis takes advantage of sequential alkylations of an indole core to rapidly construct the pentacyclic framework of the natural product. Key to the success of the synthesis was the use of a Nicholas reaction to alkylate at C2, crafting a fused seven-membered ring that is characteristic of the pentacyclic ambiguines, as well as the use of an amide-directed functionalization at C12 to set a requisite quaternary center.

A DNA-Encoded Library of Chemical Compounds Based on Common Scaffolding Structures Reveals the Impact of Ligand Geometry on Protein Recognition.

A DNA-encoded chemical library (DECL) with 1.2 million compounds was synthesized by combinatorial reaction of seven central scaffolds with two sets of 343×492 building blocks. Library screening by affinity capture revealed that for some target proteins, the chemical nature of building blocks dominated the selection results, whereas for other proteins, the central scaffold also crucially contributed to ligand affinity.

From disilene (Si=Si) to phosphasilene (Si=P) and phosphacumulene (P=C=N).

The generation of heavier double-bond systems without by- or side-product formation is of considerable importance for their application in synthesis. Peripheral functional groups in such alkene homologues are promising in this regard owing to their inherent mobility. Depending on the steric demand of the N-alkyl substituent R, the reaction of disilenide Ar2Si=Si(Ar)Li (Ar = 2,4,6-iPr3C6H2) with ClP(NR2)2 either affords the phosphinodisilene Ar2 Si=Si(Ar)P(NR2)2 (for R = iPr) or P-amino functionalized phosphasilenes Ar2(R2N)Si=Si(Ar)=P(NR2) (for R = Et, Me) by 1,3-migration of one of the amino groups.

Synthesis, characterisation and complexation of phosphino disilenes.

The treatment of disilenide Tip2SiSi(Tip)Li (1, Tip = 2,4,6-iPr3C6H2) with P-chloro phosphines affords the phosphino disilenes (2a-d; a: R = Ph, b: R = iPr, c: R = Cy, d: R = tBu), which were characterised by multinuclear NMR spectroscopy for 2a-d and a single crystal X-ray diffraction study in case of 2c. As an alternate synthetic method, the diphenyl derivative 2a could also be prepared by reaction of LiPPh2 with the thermally unstable iododisilene, Tip2SiSi(Tip)I (3), which in turn was obtained by oxidation of 1 with stoichiometric amounts of iodine. Providing the first example for a SiSi bond with an iodo functionality, disilene 3 was fully characterised by multinuclear NMR and X-ray diffraction.