A Tricyclic Dehydrorubanone and New Isomers of the Major Quinidine Metabolite

Abstract

AbstractSpiroepoxide 1 was prepared from quinidine and converted into β‐amino alcohol 3 (86% over two steps). Dihydroxylation of enantiopure oxazatricylic olefin (E)‐4 provided diastereomeric diols 5a and 5b. Stereospecific conversion of 1,2‐secondary, tertiary diol 5b into tetracyclic spiroepoxide 6 was accomplished in high yield by a one‐pot tosylation–cyclization procedure. 1,2‐Diol cleavage with NaIO4 in 80% acetic acid afforded the new tricyclic dehydrorubanone 7, containing the 4‐oxa‐7‐azatricyclo[4.3.1.03,7]‐decan‐2‐one core structure. Similarly, acetylated rubanone 9 was prepared on a 20 g scale. Reduction with NaBH4 in the presence of CeCl3 provided rubanols 10a and 10b (1:1.1). Horner–Wittig reaction of 9 with diethyl cyanomethylphosphonate was (Z)‐selective, furnishing unsaturated nitrile (Z)‐13. Conversion into the α,β‐unsaturated aldehyde (Z)‐14 and reduction afforded enartiopure allylic alcohol (Z)‐12, which is a new isomer of the key quinidine metabolite 15.