Cembranolide structures

Again, soft corals and gorgonians are a rich source of diterpenoids of 19 structural classes, some of which are specific to them (35, 36). Besides tobacco plants, cembranoid diterpenes are limited to soft corals. Lophotoxin (126) isolated from sea whips of the genus Lophogorgia is a sodium channel inhibitor (3). Xenicin (127) from the soft coral Xenia elongata and briarein A (128) from the gorgonian Briareum asbestinum represent non-cembranolide diterpenes. Diterpenoids of these classes show antimicrobial, cytotoxic, and insecticidal activities. 

A n.m.r. study of the 14-membered ring diterpenoids has been published. The Coelenterata have been the source of a number of macrocyclic diterpenoids. The cembranolides of marine origin have been reviewed. The structure (96) of a new sinulariolide, from Sinularia notanda, is also reported in this review. The soft coral Lobophytum crassum afforded (97)/ which is an isomer of lobophytolide, and crassolide (98). The keto-epoxide (99) and the 13-membered ring-contraction product (100) were obtained from another Lobophytum species. 

Cembranolide, a diterpene, is unique in that it is the only FPTase inhibitor isolated from a marine specimen, Lobophytum cristagalli (Order Alcyonacea, Family Alcyoniidae), that was collected at a 15m depth from Seychelles Island. The compound was isolated by silica gel chromatography followed by reverse phase HPLC and the structure of this 14/5-bicyclic diterpenoid (Figure 24) was elucidated by NMR and confirmed by X-ray crystallography [115]. 

Similar to cembranolide, clavaric acid was competitive with respect to the Ras-peptide substrate Kj = 1.4 jM) and non- and/or un-competitive with FPP despite having a negatively charged carboxyl group. This is only the second example of a non-nitrogenous FPTase inhibitor that is competitive with peptide substrate. These two (cembranolide and clavaric acid) structurally distinct compounds show remarkably similar profiles of the mechanism of FPTase inhibition [117]. 

Adduct (1) has been used to prepare a methylene-5-valerolactones (eq 3), common structural motifs in marine cembranolides. If a 4-trimethylsllyloxy or 4 t bulyldlmethyl-sllyloxy-2-cycloalkenone is used as substrate for the 1,4-addition, trans-a-methylene-y-butyrolactones can be prepared this strategy utilizes the steric control effect of the 4-sllyloxy substituent, which causes the nucleophile to attack at the opposing face of the double bond. 

Bowden, B.F., Coll, J.C., Engelhard , L.M., Meehan, G.V., Pegg, G.G., Tapiolas, D.M., White, A.H., and Willis, R.H. (1986b) Studies of Australian soft corals. XXXVII. Structure determination of two cembranolide diterpenes from soft corals of the genus Eff-atounaria. Aust. J. Chem., 39,123-135. 

Rodriguez, A.D., Soto, J.J., and Barnes, C.L. (2000) Synthesis of uprolide D-G analogues revision of structure of the marine cembranolides uprolide F diacetate and uprolide G acetate. J. Org. Chem., 65, 7700-7702. 

The similarities between terrestrial germacranolides and marine cembranolides are surprising, as much for their structures as for their biological properties. 

---