Flexibilene

Flexibilene, a compound isolated from marine coral, is the only known terpenoid to contain a 15-membered ring. What is the structure of the acyclic biosynthetic precursor of flexibilene Show the mechanistic pathway for the biosynthesis. 

A novel diterpenoid hydrocarbon, flexibilene (145), possessing a 15-membered ring has been obtained from the soft coral Sinulaiia flexibilis. 

The effects on coupling efficiency and regiochemical control in nonsymmetrical allyl complexes as a function of added ligand in these reactions has been determined155,156 (vide infra) and applied in the synthesis of flexibilene and humulene.157... 

Cyeloalkenes (8, 483). The last step in a synthesis of flexibilene (2), a 15-membered-ring diterpene, involved cyclization of the keto-aldehyde 1, catalyzed with the active titanium metal prepared by reduction of TiClj with Zn-Cu in DME. A mixture of two cyclized products is formed, in which 2 is the major constituent.1... 

McMuriy reactions also work very well intramolecularly, and turn out to be quite a good way of making cyclic alkenes, especially when the ring involved is medium or large (over about eight members). For example, the natural product flexibilene, with a 15-membered ring, can be made by cycliz-... 

The precursor to flexibilene is formed from the reaction of famesyl diphosphate and isopentenyl diphosphate. 

The precursor cyclizes by the now-familiar mechanism to produce flexibilene. 

Flexibilene (103), a 15-membered diterpene, which was not isolated until 1976 from the coral Smularia flexibUis [77], could be obtained in 1987 by addition of a 10 M solution of the dicarbonyl compound 102 to TiClVzinc within 32 h in 53% yield [761]. 

Here is an example from the McMurry flexibilene synthesis quoted in chapter 1. An alkyne 127 with a protected aldehyde group reacts with Cp2ZrHCl to give a vinyl zirconium complex 128 which is coupled to a palladium-allyl complex in the next step. The double bond so produced is present with the same E configuration in the final product. It is marked 129 with an arrow in the diagram.28... 

Figure 14.2 shows a synthesis of the diterpene, flexibilene, which uses metal-based reagents in almost every step one of the key steps is nucleophilic attack of a vinylzirconium species on an allylpalladium complex. 

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