抄録
Mediterraneols A,B 1,2, isolated from Cystoseira mediterranea, inhibit the mitotic cell division fertilized urchin eggs and exhibit antitumor activity against P388 leukemia. The central structural feature of these novel diterpenoids is the bicyclo[4.2.1]nonane framework with three contiguous quarternary carbon centers. On the basis of the new method for efficient construction of bicyclo[4.2.1]nonane skeleton by skeletal rearrangement of 6-4 fused ring system, which has been developed by us, we studied the total synthesis of Mediterraneols. Our convergent synthetic plan derived from a retrosynthetic analysis, was designed to assemble two segments, the hydroquinone side-chain 7 and the bicyclo[4.2.1]nonane moiety 8. Thus, the left-wing 7 was synthesized readily from 1-bromo-2,5-dimethoxy-3-methylbenzene 33 as a starting material. Synthesis of the key component, right-wing 8 was undertaken starting from tert-butylcyclohexenone 11. Utilizing our method, bicyclo[4.2.1]nonanone 16 was synthesized successfully from allene-photoadduct 13 by acid-catalyzed rearrangement with TiCl_4 and BCl_3. The ketone 16 was transformed to the aldehyde 32 through introduction of the methyl and allyl groups at C(7) of the ketone 12. As a model study, bicyclo[4.2.1]nonane-2,4-dione 41 was also synthesized from bicyclo[4.2.1]nonanone 6 derived by skeletal rearrangement of the 6-4 ketone 5.
