SYNTHESIS OF THE TUMOR INHIBITORY TOBACCO CONSTITUENTS ALPHA-2,7,11-CEMBRATRIENE-4,6-DIOL AND BETA-2,7,11-CEMBRATRIENE-4,6-DIOL BY DIASTEREOSELECTIVE [2,3] WITTIG RING CONTRACTION

The synthesis of β-CBT (25) and a-CBT (47), cembranoid constituents of tobacco with plant growth inhibitory and antitumor properties, is described. The route employs [2,3] Wittig ring contraction of the 17-membered propargylic ethers 8a or 8c to construct the 14-membered carbocyclic cembrane nucleus with the requisite syn relationship at C-l and C-6. The (E)-enone 16 was prepared by 1,4-addition of Me2CuLi to the derived ynone 13. Epoxidation of enone 16b with H202, NaOH afforded the β-epoxide 18 stereoselectively (7:1). Reductive elimination of the epoxy mesylate 22 and hydrogenation of the isopropenyl double bond afforded racemic β-CBT (25). [2,3] Wittig ring contraction of the 6R enantiomer of ether 8c afforded the nonracemic anti, syn alcohol 9c as the major product. This intermediate was converted to natural a-CBT (47) by a sequence involving directed epoxidation of the allylic alcohol 43 and reductive elimination of the mesylate derivative 46. © 1990, American Chemical Society. All rights reserved.