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Interest in saturated N-heterocycles as scaffolds for the synthesis of bioactive molecules is increasing. Reliable and predictable synthetic methods for the preparation of these compounds, especially medium-sized rings, are limited. We describe the development of SnAP (Sn amino protocol) reagents for the transformation of aldehydes into seven-, eight- and nine-membered saturated N-heterocycles. This process occurs under mild, room-temperature conditions and offers exceptional substrate scope and functional-group tolerance. Air- and moisture-stable SnAP reagents are prepared on a multigram scale from inexpensive starting materials by simple reaction sequences. These new reagents and processes allow widely available aryl, heteroaryl and aliphatic aldehydes to be converted into diverse N-heterocycles, including diazepanes, oxazepanes, diazocanes, oxazocanes and hexahydrobenzoxazonines, by a single synthetic operation.

Catechol dehydroxylation is a central chemical transformation in the gut microbial metabolism of plant- and host-derived small molecules. However, the molecular basis for this transformation and its distribution among gut microorganisms are poorly understood. Here, we characterize a molybdenum-dependent enzyme from the human gut bacterium Eggerthella lenta that dehydroxylates catecholamine neurotransmitters. Our findings suggest that this activity enables E. lenta to use dopamine as an electron acceptor. We also identify candidate dehydroxylases that metabolize additional host- and plant-derived catechols. These dehydroxylases belong to a distinct group of largely uncharacterized molybdenum-dependent enzymes that likely mediate primary and secondary metabolism in multiple environments. Finally, we observe catechol dehydroxylation in the gut microbiotas of diverse mammals, confirming the presence of this chemistry in habitats beyond the human gut. These results suggest that the chemical strategies that mediate metabolism and interactions in the human gut are relevant to a broad range of species and habitats.

Substituted piperazines and morpholines are valuable structural motifs in biologically active compounds, but are not easily prepared by contemporary cross-coupling approaches. In this report, we introduce SnAP reagents for the transformation of aldehydes into N-unprotected piperazines and morpholines. This approach offers simple, mild conditions compatible with aromatic, heteroaromatic, aliphatic, and glyoxylic aldehydes and provides mono- and disubstituted N-heterocycles in a single step.

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