Salvinorin A (1) is natural hallucinogen that binds the human κ-opioid receptor. A total synthesis has been developed that parlays the stereochemistry of l-(+)-tartaric acid into that of (-)-1 via an unprecedented allylic dithiane intramolecular Diels-Alder reaction to obtain the trans-decalin scaffold. Tsuji allylation set the C9 quaternary center and a late-stage stereoselective chiral ligand-assisted addition of a 3-titanium furan upon a C12 aldehyde/C17 methyl ester established the furanyl lactone moiety. The tartrate diol was finally converted into the C1,C2 keto-acetate.

Health-care workers, laboratorians and overdose prevention centers rely on commercial immunoassays to detect the presence of fentanyl; however, the cross-reactivity of fentanyl analogs with these kits is largely unknown. To address this, we conducted a pilot study evaluating the detection of 30 fentanyl analogs and metabolites by 19 commercially available kits (9 lateral flow assays, 7 heterogeneous immunoassays and 3 homogenous immunoassays). The analogs selected for analysis were compiled from the Drug Enforcement Administration and National Forensic Laboratory Information System reports from 2015 to 2018. In general, the immunoassays tested were able to detect their intended fentanyl analog and some closely related analogs, but more structurally diverse analogs, including 4-methoxy-butyryl fentanyl and 3-methylfentanyl, were not well detected. Carfentanil was only detected by kits specifically designed for its recognition. In general, analogs with group additions to the piperidine, or bulky rings or long alkyl chain modifications in the N-aryl or alkyl amide regions, were poorly detected compared to other types of modifications. This preliminary information is useful for screening diagnostic, forensic and unknown powder samples for the presence of fentanyl analogs and guiding future testing improvements.

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