Synthesis of triterpenoid-based ring-A azepanone and gem-3-nitro-3-chloro- derivatives by ozonolysis of 3-oximino-28-oxoallobetulin under normal and acidic solvolysis conditions

Abstract

It was found that ozonolysis of 3-oximino-28-oxoallobetulin under normal conditions (CHCl3, 0 °C) led to the preferred formation of azepanone (lactam) ring-A (61%) and partial removal of oximino-moiety to 28-oxoallobetulone (28%). In the case of ozonation under acidic conditions (5% vol. HCl in CHCl3, 0 °C) the attendant formation of minor products of 28-oxoallobetulin was observed, besides lactam (48%), with a total yield of 28%. These were 2,2-dichloroazepanone, (3S)-3-nitro-3-chloro-, 2-cyano-3,4-seco-4(23)-en-, 2-cyano-3,4-seco-23-nor-4,28-dioxo-defivatives and also a mixture of A-seco-24-chlorine-contained products. 3-Nitro-3-chloro-28-oxoallobetulone was synthesized for the first time as a single (3S)-diastereoisomer with a yield of 9% in the reaction with ozone, while oxidation of 3-oximino-28-oxoallobetulin with oxone® in the presence of NaCl and H2O led to the mixture of (3R)- and (3S)-diastereomers. The application of ozone in the oxidative synthesis of ring-A lactams from 3-oximinotriterpenoids seems to be an alternative route to the Beckmann rearrangement.