A Tricyclic Dehydrorubanone and New Isomers of the Major Quinidine Metabolite

Abstract

Abstract Spiroepoxide 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 NaIO 4 in 80% acetic acid afforded the new tricyclic dehydrorubanone 7 , containing the 4‐oxa‐7‐azatricyclo[4.3.1.0 3,7 ]‐decan‐2‐one core structure. Similarly, acetylated rubanone 9 was prepared on a 20 g scale. Reduction with NaBH 4 in the presence of CeCl 3 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 .