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 taxold taxinine B via four steps gave a corresponding aldehyde 5, which afforded a new dimeric taxold 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 taxold 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 taxold 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. (C) 2000 Elsevier Science Ltd.