Oxetanes and azetidines are increasingly valued in drug discovery due to favourable lipophilicity, molecular weight and scaffolding properties. Oxetanes in particular offer intriguing potential as carbonyl replacement groups. However, synthetic methods to generate derivatives of these 4-membered heterocycles remain limiting. This presentation will disclose our divergent approaches for the synthesis of novel oxetanes and azetidines bearing medicinally relevant substituents. We have specifically targeted new fragments, building blocks, and bioisosteres appropriate for medicinal chemistry programs.<br/><br/>Strategies will be presented to generate new structural classes, invoking i) new C–C bond forming cyclization modes, and ii) the controlled generation of oxetane and azetidine carbocations for reaction with C, S, O and N nucleophiles. Assessment of these motifs for chemical and metabolic stability, as well as studies on their suitability as bioisosteres will be included.

Synthesis of new chemical motifs for drug discovery: 4-Membered heterocycles as fragments and bioisosteres

2019 Fall National Meeting

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