CAM4066, a specific CK2α kinase inhibitor, is anchored in the cryptic αD pocket outside the active site and inserts a “warhead” into the active site, blocking ATP binding and thereby inhibiting the kinase.

Graphical abstract

We describe the development of a CAM4712, a novel CK2α inhibitor which does not interact with the ATP binding site and shows improved properties over the first-generation inhibitor CAM4066.

The asymmetric synthesis of helicenes … … by a Fischer indolization catalyzed by a SPINOL-derived phosphoric acid is reported by B. List et al. in their Communication on page 5202 ff. The catalyst is designed for long-range control and bears extended p-surfaces at the 3,3'-position. It creates a chiral nanometer-sized pocket, which enables p-p stacking interactions between the substituents and the reactive intermediate. A variety of (di)azahelicenes were obtained with good to excellent yields and enentioselectivities.

Es wird über die erste asymmetrische organokatalytische Synthese von Helicenen berichtet. Eine neue SPINOL‐abgeleitete Phosphorsäure mit ausgedehnten π‐Substituenten katalysiert die asymmetrische Synthese von Helicenen über eine enantioselektive Fischer‐Indolisierung. Eine Vielzahl von Azahelicenen und Diazahelicenen konnte auf diese Weise mit guten bis sehr guten Ausbeuten und Enantioselektivitäten erhalten werden.

The asymmetric synthesis of helicenes … … by a Fischer indolization catalyzed by a SPINOL-derived phosphoric acid is reported by B. List et al. in their Communication on page 5202 ff. The catalyst is designed for long-range control and bears extended p-surfaces at the 3,3'-position. It creates a chiral nanometer-sized pocket, which enables p-p stacking interactions between the substituents and the reactive intermediate. A variety of (di)azahelicenes were obtained with good to excellent yields and enentioselectivities.

Different organic promoters have been successfully employed in asymmetric oxidations with hydrogen peroxide and molecular oxygen as environmentally benign oxidants. In this manuscript, we illustrate developments achieved in this area to access chiral epoxides, sulfoxides, gamma-lactones, alfa-hydroxylated carbonyl compounds, and derivatives thereof

Fragment‐based drug discovery is now widely adopted for lead generation in the pharmaceutical industry. However, fragment screening collections are often predominantly populated with flat, 2D molecules. Herein, we describe a workflow for the design and synthesis of 56 3D disubstituted pyrrolidine and piperidine fragments that occupy under‐represented areas of fragment space (as demonstrated by a principal moments of inertia (PMI) analysis). A key, and unique, underpinning design feature of this fragment collection is that assessment of fragment shape and conformational diversity (by considering conformations up to 1.5 kcal mol −1 above the energy of the global minimum energy conformer) is carried out prior to synthesis and is also used to select targets for synthesis. The 3D fragments were designed to contain suitable synthetic handles for future fragment elaboration. Finally, by comparing our 3D fragments with six commercial libraries, it is clear that our collection has high three‐dimensionality and shape diversity.