Novel Dimeric Taxoids via Highly Regio- and Stereospecific Diels–Alder Cycloadditions of Taxinine B and Taxicine I Derivatives

Oxidation of 20-hydroxy-4,5-ene-7-oxotaxinine 4 derived from a natural taxoid taxinine B via four steps gave a corresponding aldehyde 5, which afforded a new dimeric taxoid 6 through regio- and stereospecific hetero Diels–Alder cycloaddition. Similar hetero Diels–Alder reaction of 4:5,6:7-diene aldehyde 13 gave two new dimeric taxoids 14 and 15. In addition, Lewis acid-catalyzed Diels–Alder reaction of 20-hydroxy-4:5,6:7-diene taxoid 12 with N-methylmaleimide led to cycloadduct exo-16 and γ-butyrolactone endo-17, while a similar Lewis acid-catalyzed Diels–Alder reaction of 12 with taxoid 7a yielded only cycloadduct exo-18. 7a and 7b, the two isomers of alcohol 4, yielded two 5-ethyl substituted derivatives 8 and 9 through highly stereoselective Michael addition in the presence of diethylaluminum chloride. The structure and stereochemistry of the dimers were established by spectroscopic experiments including 2D NMR studies.