Conglomerate Crystallization in the Cambridge Structural Database (2020-2021).

Conglomerate crystals are materials capable of undergoing spontaneous resolution and were responsible for the discovery of molecular chirality. Their relevance to modern chemical and crystallographic sciences has been hindered by the difficulty in identifying and searching materials with this characteristic ability to spontaneously bias their own enantioenrichment. With the release of the November 2021 distribution of the Cambridge Structural Database (CSD) (version 5.

Identifying a Hidden Conglomerate Chiral Pool in the CSD.

Conglomerate crystallization is the spontaneous generation of individually enantioenriched crystals from a nonenantioenriched material. This behavior is responsible for spontaneous resolution and the discovery of molecular chirality by Pasteur. The phenomenon of conglomerate crystallization of chiral organic molecules has been left largely undocumented, with no actively curated list available in the literature.

Enantioselective synthesis of ammonium cations.

Control of molecular chirality is a fundamental challenge in organic synthesis. Whereas methods to construct carbon stereocentres enantioselectively are well established, routes to synthesize enriched heteroatomic stereocentres have garnered less attention. Of those atoms commonly present in organic molecules, nitrogen is the most difficult to control stereochemically.

Regioselective Functionalization of 7-Azaindole by Controlled Annular Isomerism: The Directed Metalation-Group Dance.

The regioselective functionalization of 7-azaindole by controlled annular isomerism employing a directed metalation-group migration is reported. The N7 carbamoyl azaindoles undergo regioselective metalation and quenching with an electrophile to furnish C6-substituted derivatives which, in the presence of a catalytic amount of ClCONR promotes a carbamoyl group shift or dance from N7 to N1. A second directed metalation/electrophile quench sequence leads to 2,6-substituted azaindoles.

Directed Remote Lateral Metalation: Highly Substituted 2-Naphthols and BINOLs by In Situ Generation of a Directing Group.

A general synthesis of highly substituted 2-naphthols based on a new carbanionic reaction sequence is demonstrated. The reaction exploits the dual nature of lithium bases consisting of consecutive ring opening of readily available coumarins with either LiNEt or LiNiPr into Z-cinnamamides, thus generating a directing group in situ and allowing, by conformational freedom, a lateral directed remote metalation for ring closure to give the aryl 2-naphthols in good to excellent yields. These transformations can be combined to provide a more efficient one-pot process.

Sequence-Specific β-Peptide Synthesis by a Rotaxane-Based Molecular Machine.

We report on the synthesis and operation of a three-barrier, rotaxane-based, artificial molecular machine capable of sequence-specific β-homo (β) peptide synthesis. The machine utilizes nonproteinogenic β-amino acids, a class of amino acids not generally accepted by the ribosome, particularly consecutively. Successful operation of the machine via native chemical ligation (NCL) demonstrates that even challenging 15- and 19-membered ligation transition states are suitable for information translation using this artificial molecular machine.

Tying a Molecular Overhand Knot of Single Handedness and Asymmetric Catalysis with the Corresponding Pseudo-D-Symmetric Trefoil Knot.

We report the stereoselective synthesis of a left-handed trefoil knot from a tris(2,6-pyridinedicarboxamide) oligomer with six chiral centers using a lanthanide(III) ion template. The oligomer folds around the lanthanide ion to form an overhand knot complex of single handedness. Subsequent joining of the overhand knot end groups by ring-closing olefin metathesis affords a single enantiomer of the trefoil knot in 90% yield.

Goldberg Active Template Synthesis of a [2]Rotaxane Ligand for Asymmetric Transition-Metal Catalysis.

We report on the active template synthesis of a [2]rotaxane through a Goldberg copper-catalyzed C-N bond forming reaction. A C2-symmetric cyclohexyldiamine macrocycle directs the assembly of the rotaxane, which can subsequently serve as a ligand for enantioselective nickel-catalyzed conjugate addition reactions. Rotaxanes are a previously unexplored ligand architecture for asymmetric catalysis.

A machine-assisted flow synthesis of SR48692: a probe for the investigation of neurotensin receptor-1.

Here we report the direct comparison of a conventional batch mode synthesis of Meclinertant (SR48692, 1), a neurotensin receptor-1 antagonist, with its machine-assisted flow chemistry alternative. By using these enabling tools, combined with solid-supported reagents and scavengers, many process advantages were observed. Care, however, must be taken not to convert these techniques into expensive solutions to problems that do not exist.

Palladium-catalyzed cross-coupling: a historical contextual perspective to the 2010 Nobel Prize.

In 2010, Richard Heck, Ei-ichi Negishi, and Akira Suzuki joined the prestigious circle of Nobel Laureate chemists for their roles in discovering and developing highly practical methodologies for C-C bond construction. From their original contributions in the early 1970s the landscape of the strategies and methods of organic synthesis irreversibly changed for the modern chemist, both in academia and in industry. In this Review, we attempt to trace the historical origin of these powerful reactions, and outline the developments from the seminal discoveries leading to their eminent position as appreciated and applied today.

Cancer, chemistry, and the cell: molecules that interact with the neurotensin receptors.

The literature covering neurotensin (NT) and its signalling pathways, receptors, and biological profile is complicated by the fact that the discovery of three NT receptor subtypes has come to light only in recent years. Moreover, a lot of this literature explores NT in the context of the central nervous system and behavioral studies. However, there is now good evidence that the up-regulation of NT is intimately involved in cancer development and progression.