Cembranoids total synthesis

Dauben et al. [153] successfully applied this procedure to the total synthesis of the cembranoid crassin acetate methyl ether (258). As shown in Scheme 86, the keto aldehyde 256 was treated with TiClj/Zn-Cu in refluxing DME to give the cyclic olefin 257 in 65% yield (E Z = 4 3). The germacrane sesquiterpenes have also been synthesized using this method [154],... 

The closure of the macrocyclic ring by means of an intramolecular 8 2 reaction is a straightforward approach, and sulfur-stabilized carbanion alkylation has been successfully applied in the synthesis of 14-membered cembranoids. The synthesis of nephthenol (40) and cembrene A (59) is an example of this methodology. In Li and Yue s report, the total synthesis of ( )-sarcophytol M (17) was achieved from ger-aniol (137) through 12 steps and in 8.9% overall yield with an intramolecular nucleophilic addition of a sulfur-stabilized carbanion to a ketone as a key step. This example is the first of the closure of a macrocyclic ring with the intramolecular nucleophihc addition of a sulfur-stabilized carbanion to a ketone (Scheme 6-7). 

The total synthesis of the cembranoid diterpene (+)-crassin acetate methyl ether was accomplished by W.G. Dauben et al. In the final stages of the total synthesis, the sensitive a-methylene group was introduced onto the six-membered lactone by using the Eschenmoser methenylation procedure. The lactone was deprotonated with LDA and then treated with Eschenmoser s salt. In the second step, the dimethylamino group was exhaustively methylated and the quaternary ammonium salt underwent a smooth Hofmann elimination upon deprotonation with DBU. 

Paquette, L.A., Wang, T.-Z., Philippo, C.M.G., and Wang, S., Total synthesis of the cembranoid diterpene lactone (-i-)-cleomeolide. Some remarkable conformational features of nine-membered belts linked in a 2,6-fashion to a methylenecyclohexanc core, J. Am. Chem. Soc., 116, 3367, 1994. Moskva, V.V., and Razumov, A.I., Phosphinic and phosphinous acids. Part 34. Phosphorylated 1,3-dioxolanes, Trans. Kazan. Khim.-Tekhnol. Inst., 34, 273, 1965 Chem. Abstr, 68, 39729y, 1968. Razumov, A.L, and Gurevich, P.A., Synthesis of phosphorylated 1,3-dioxoles, Zh. Obshch. Khim., 38, 944, 1968 J. Gen. Chem. USSR (Engl. Transl.), 38, 909, 1968. 

Tang B, Bray CD, Pattenden G, Rogers J. Total synthesis of (+)-Z-deoxypukalide, a furanobutenolide-based cembranoid isolated from the pacific octocoral Leptotgorgia spp. Tetrahedron 2010 66 2492-2500. 

Ellis JM, Crimmins MT. Strategies for the total synthesis of C2-C11 cyclized cembranoids. Chem. Rev. 2008 108 5278-5298. 

Takayanagi, H., Kitano, Y, and Morinaka, Y. (1994) Total synthesis of sarcophytol A, an anticarcinogenic marine cembranoid. /. Org. Chem, 59,2700-2706. 

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