Heteroatom Analogues of Hydrocodone: Synthesis and Biological Activity

Heteroatom analogues of hydrocodone, in which the <i>N</i>-methyl functionality was replaced with oxygen, sulfur, sulfoxide, and sulfone, were prepared by a short sequence from the ethylene glycol ketal of hydrocodone; a carbocyclic analogue of bisnorhydrocodone was also prepared. The compounds were tested for receptor binding and revealed moderate levels of activity for the sulfone analogue of hydrocodone

<i>Neocosmospora</i> sp.-Derived Resorcylic Acid Lactones with in Vitro Binding Affinity for Human Opioid and Cannabinoid Receptors

Bioassay-guided fractionation of a fungus <i>Neocosmospora</i> sp. (UM-031509) resulted in the isolation of three new resorcylic acid lactones, neocosmosin A (<b>2</b>), neocosmosin B (<b>3</b>), and neocosmosin C (<b>4</b>). Three known resorcylic acid lactones, monocillin IV (<b>1</b>), monocillin II (<b>5</b>), and radicicol (<b>6</b>), were also isolated and identified. The structures of these compounds were established on the basis of extensive 1D and 2D NMR spectroscopic analysis, mass spectrometric (ESIMS) data, and X-ray crystallography. Compounds <b>4</b>–<b>6</b> show good binding affinity for the human opioid receptors. These findings have important implications for evaluating the potential psychoactive effects with this class of compounds