Stereodynamic properties of medium-ring benzo-fused nitrogenous heterocycles: benzodiazepines, benzazepines, benzazocines, and benzazonines

A twist of nature – the significance of atropisomers in biological systems

“…12 In recent years, there has also been a creative appreciation of 'non-traditional' atropisomerism associated with diazepine moieties. 13 Though these molecules themselves do not contain a stereogenic carbon or biaryl axis, they exhibit atropisomerism through conformational inversion of the non-planar ring. The diazepine moiety forms the core of a variety of natural effector molecules; though a variety of synthetic drugs, like benzodiazepine ( Figure 3, Compound 4), are more widely known.…”

“…Additionally, phenotypic analysis of cells treated with 12, 14, and 16 showed elongated rod-like cells; an indicator for the induction of the bacterial SOS pathway in response to DNA interference. However, due to the fact that all compounds (11)(12)(13)(14)(15)(16) showed a reduction in B. subtilis growth, it was assumed that this was just one pathway through which inhibition occurred, and was reliant on the absolute configuration of the atropdiastereomers. This is promising as it evidences variable activity of therapeutic compounds based on their atropisomeric configuration, however the group concluded it is likely the natural products may have an additional, potentially novel, mode of action though this requires further investigation.…”

Annulation of Eight- to Ten-Membered Oxaza Rings to the Benzo[b]thiophene System by Intramolecular Nucleophilic Displacement

“…In the 13 C NMR the presence of the lactam carbonyl group was consistent with signals in the region of δ166-178. Stereochemically stable rotational isomers in the medium ring products are possible by analogy with the related bioisosteric naphthalene-ring fused oxaza systems [7][8][9] , and some tentative evidence was seen for these in 1a-c on the basis of the NMR spectra.…”

“…[1] Such compounds are of inherent chemical interest and are also of significance as novel scaffolds for pharmaceutical development, [2][3][4] particularly 8-membered systems. [5][6][7][8][9] As part of some structure-pharmacological activity studies on benzo [b]thiophene-based potentiators of the action of serotonin, we required systems in which amide functionality at the 2-position of the benzo [b]thiophene was incorporated in a semi-flexible ring system, while retaining an electronegative group at the 3-position. Fused medium sized [1,5]-oxaza systems 1 (Scheme 1) were thus considered as synthetic targets.…”

Synthesis and X-ray Structural Studies of a Substituted 2,3,4,5-Tetrahydro-1H-3-benzazonine and a 1,2,3,5-Tetrahydro-4,3-benzoxazonine

“…Annulated medium-ring heterocycles have attracted significant research attention owing to the vast array of systems possible with potential for different chemical and biological properties [1][2][3][4]. For example, some 3-benzazonines with a nine-membered ring show 5-HT2A antagonist activity [5], while the eight-membered ring-containing benzoxazocines display a range of biological properties including analgesic [6] and NK1 (neurokinin receptor) inhibitory activity [7].…”