RESUMEN
The semisynthesis and biological activity of paclitaxel (Taxol) analogues in which the oxygen atom in ring D is substituted by a sulfur or a selenium atom is presented. These derivatives were synthesized and tested in order to make more transparent the role of the oxetane ring in the biological activity of paclitaxel. The sulfur derivatives were found to be less active than paclitaxel in biological assays, while the selenium derivative could not be converted to its 4-acyl analogue. The results with the sulfur analogues suggest that the oxygen atom in the oxetane ring plays an important role in the mechanism by which paclitaxel exhibits its anticancer activity.
RESUMEN
Positional preferences for para benzylic oxygenation of tetrahydronaphthalenes by 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ)-aqueous dioxane were investigated by comparing the tetralone products from 6-hydroxy-7-methoxy- and 6-acetoxy-7-methoxy-1,2,3,4-tetrahydronaphthalene. The directing influence by an aromatic substituent on para benzylic oxygenation was in the order OH > OMe > OAc. Consistent with this finding were results obtained from lignan analogues. Treatment of (+)-beta-conidendryl alcohol with DDQ in dry dioxane resulted in the intramolecular bridging by one of two primary hydroxy groups to the benzylic position, giving an oxabicyclo[3.2.1]octane. Similar treatment of (+)-dimethyl-beta-conidendryl alcohol resulted in bridging by the alternate primary hydroxyl group to the benzhydrylic carbon giving an isomeric oxabicyclo[3.2.1]octane.
