| Popis: |
A novel synthesis of 11,12-dimethoxyabieta-8,11,13-triene ( 4 ), involving the biomimetic cyclization of allylic alcohol 5 is described. This represents a formal total synthesis of taxodione ( 1 ), a tumor-inhibitory diterpenoid quinone methide. Treatment of the sodium salt of 8 with allyl bromide gave a 91% yield of allyl ether 19 which readily underwent a Claisen rearrangement to give (after methylation with dimethyl sulfate) the dimethoxy olefin 21 in 90% yield. Hydroboration with disiamylborane, followed by oxidative work-up gave alcohol 17 in 98% yield. Oxidation with Collins' reagent afforded 22 in 83% yield. which, upon treatment with isopropenylmagnesium bromide, gave allylic alcohol 23 in 91% yield. Conversion of 23 into chloro ketone 25 was readily effected in 80% yield via a chloro ketal Claisen rearrangement. This substance afforded epoxide 26 in 94% yield when treated with isopropenyllithium. Reduction of 26 with lithium in liquid ammonia gave the desired substrate 5 in 93% yield. When 5 was treated with trifluoroacetic acid in methylene chloride at ca −45° for 45 min, a 90% yield of the desired tricyclic material 6 was obtained. Conversion of 6 to dl -11,12-dimethoxy-abieta-8,11,13-triene ( 4 ) was effected in 59% yield by ruthenium tetroxide oxidation (to give 30 ) followed by sodium cyanoborohydride reduction of the corresponding tosylhydrazone of 30 . Resolution of 30 involved the separation of the diastereomeric ketals 31 . Conversion of d - 30 into d -11,12-dimethoxyabieta-8,11,13-triene ( 4 ) was effected in the aforementioned manner used in the dl -series. |
