Spiro-diterpenes

Spiro diterpenes E. viscida, as the name implies, is a species whose branches and leaves carry a sticky resin and this appearance gave rise to the vernacular name of varnish bush. The resin consists largely of material extractable into base. The major components are two diterpene acids (131,132) which disclosed a new diterpene skeleton (111). Although a small amount of the crystalline dihydroxy acid (131) could be obtained after tedious separation, as often found with Eremophila resins, the process was simplified by methylation of the crude acidic fraction and separation of the methyl esters. 

ABSTRACT Marine invertebrates such as ascidians, sponges and others are a prolific source of bioactive secondary metabolites. We have isolated a variety of marine natural products from the Okinawan marine invertebrates by using the sea urchin egg assay. Our recent work, the isolation, structure determination and activities of chlorinated macrolides, sesterterpenic acids, a bromotyrosine derivative, acetogenin derived endoperoxides, diterpene alkaloids, sesquiterpene quinones and spiro-sesquiterpenes, is presented in this article. The syntheses of these metabolites are also described. 

A single electron transfer is again involved in formation of the ketone (14) together with the well-known intramolecular adduct (15) when carvone is irradiated in the presence of triethylamine (Givens et al.). In related work, Bischof and Mattay showed that the presence of triethylamine deflected the normal course of intramolecular photoaddition within the enones (16) to produce the spiro compounds (17) preferentially. Regio- and stereospecific adducts from cyclopentenones and the bicyclo[2.2.1]heptene (18) have been used by Salomon et al. as a route to spatane diterpenes. Photoadditions of alkenes to enones can give oxetans and/or cyclobutanes. Cruciani et al. have reported that the use of acetonitrile as solvent favours the formation of cyclobutanes. The oxetanes may be formed via a contact ion pair whereas the cyclobutanes may arise from an exciplex. 

The viscidanes exhibit an antipodal configuration at C7 compared to the bisabolane, serrulatane and decipiane diterpenes. This difference may reflect the involvement of a 3/ ,6 -acyclic precursor (211), or 3S,6E-, which cyclizes to the lS,7/ -intermediate (212) (Scheme 51). A 1,2-hydride shift with displacement of X would generate the tertiary carbocation (213) which could alkylate the Re-facc of CIO. The spiro-ring system produced (214) contains the 1,4-trans-disubstitution on the cyclopentane ring observed for the viscidane nucleus. A 1,5-hydride shift of the quasi-a ial allylic hydrogen in 214 and allylic rearrangement, with net yn-addition of water, completes the elaboration of the nucleus. Circumstantial support for the last step can be enlisted... 

Unsaturated P-dicarbonyl compounds with catalytic I2—PPh3 underwent an efficient and stereoselective spiroannulation to afford the corresponding spiro enol ether derivatives with complete regio- and stereoselectivity, which also applied in the first total synthesis of the antiinflammatory diterpene negundoin A and a naturally occurring trypanocidal aldehyde (13CC10257). 

Simple mono-olefinic derivatives (206) of /3-diketones or /3-keto-esters can be cyclized efficiently using SnCU the method can also be applied to the synthesis of bicyclic and spiro-cyclic systems.A closely related cyclization using monoacetylenes, e.g. (207) also works well to give (208), a potential precursor of the clerodin diterpenes. ... 

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