TOTAL SYNTHESIS OF (+ -)-TETRAMETHYLMEDITERRANEOL-B/

A diterpenoid having the structure proposed for the tetramethylated de rivative 2 of mediterraneol B (1) has been synthesized in a stereocont rolled manner via coupling between the hydroquinone side chain 7 and t he bicyclo[4.2.1]nonane core 8 followed by buildup of the 1,3-diketone functionality. The hydroquinone segment 7 was prepared easily accordi ng to the reported method. Synthesis of the key component 8 was undert aken starting from tert-butylcyclohexenone 11. The cornerstone of the synthesis is the acid-catalyzed rearrangement of bicyclo[4.2.0]octanon e 10 to the ketone 9 which has the bicyclononane skeleton and has clue s for further manipulation. As a model study for introduction of the 1 ,3-diketone functionality, bicyclo[4.2.1]nonane-2,4-dione 43 was also prepared. Methylation of the penultimate intermediate 62 under conditi ons reported in isolation of the natural product did not give the tetr amethyl ether 2 but a mixture of the trimethyl ethers 64 and 65. With Me(3)OBF(4) and Proton Sponge, the transformation to 2 was successfull y achieved. The structure of the synthetic 2 was secured by the X-ray crystallographic structure analysis of the key compound 60. However, t he difference between the spectra of the synthetic 2 and those of the compound derived from the natural product suggests the structure of th e latter is incorrect and requires revision.