Unrestricted: Pseudoephenamine is introduced as a versatile chiral auxiliary and an alternative to pseudoephedrine in asymmetric synthesis. It is free from regulatory restrictions and leads to remarkable stereocontrol in alkylation reactions, especially in those that form quaternary carbon centers. Amides derived from pseudoephenamine exhibit a high propensity to be crystalline substances, and provide sharp, well‐defined signals in NMR spectra.

The effect of relative water content on the luminescence properties and speciation of Eu3+ ions in solutions of EuCl3 in the binary solvent mixture water/[BMI]Cl is presented, where [BMI]Cl is the ionic liquid (IL) 1-butyl-3-methylimidazolium chloride. Using luminescence techniques, the binding properties of water to Eu3+ are determined for samples with mole ratios of water-to-IL ranging from 0 to 5. Very little water binds to Eu3+ at mole ratios of water-to-IL less than 1, above which binding increases rapidly with increasing water concentration. It is shown that only certain hydration numbers for Eu3+ complexes are stable in the water/IL solutions. The data presented suggest that the Eu3+ species present are [EuClx]3-x, [EuCly(H2O)3-4]3-y, [EuClz(H2O)6]3-z, and [Eu(H2O)8-9]3+ (where x > y > z). Comparison of the positions of the 5D0<--7F0 transitions of the Eu3+ complexes in IL solution with those of model crystal systems provides insight into the extent of Cl- complexation. This study suggests that [BMI]Cl is a promising medium for luminescent lanthanide (Ln) compounds due to the low-energy phonon environment of the [LnClx]3-x complex and to the fact that moderate water contamination does not result in direct binding of water to Ln3+, which would result in luminescence quenching.

Hyperactivation of mTOR kinase by mutations in the PI3K/mTOR pathway or by crosstalk with other mutant cancer drivers, such as RAS, is a feature of many tumors. Multiple allosteric inhibitors of mTORC1 and orthosteric dual inhibitors of mTORC1 and mTORC2 have been developed as anticancer drugs, but their clinical utility has been limited. To address these limitations, we have developed a novel class of “bi-steric inhibitors” that interact with both the orthosteric and the allosteric binding sites in order to deepen the inhibition of mTORC1 while also preserving selectivity for mTORC1 over mTORC2. In this report, we describe the discovery and preclinical profile of the development candidate RMC-5552 and the in vivo preclinical tool compound RMC-6272. We also present evidence that selective inhibition of mTORC1 in combination with covalent inhibition of KRASG12C shows increased antitumor activity in a preclinical model of KRAS G12C mutant NSCLC that exhibits resistance to KRASG12C inhibitor monotherapy.

The utility of pseudoephenamine as a chiral auxiliary for the alkylative construction of quaternary α-methyl α-amino acids is demonstrated. The method is notable for the high diastereoselectivities of the alkylation reactions, for its versatility with respect to electrophilic substrate partners, and for its mild hydrolysis conditions, which provide α-amino acids without salt contaminants. Alternatively, α-amino esters can be obtained by direct alcoholysis.

Uneingeschränkt: Pseudoephenamin wird als vielseitiges chirales Auxiliar und als eine Alternative zu Pseudoephedrin in der asymmetrischen Synthese vorgestellt. Es hat keine regulatorischen Einschränkungen und führt zu bemerkenswerter Stereokontrolle in Alkylierungen, vor allem in solchen, die ein quartäres Kohlenstoffzentrum aufbauen. Aus Pseudoephenamin erhaltene Amide sind meist kristalline Substanzen und ergeben scharfe, gut definierte Signale in ihren NMR‐Spektren.