Aplysiatoxins

By interfering with any one of the many phases associated with these second messenger pathways, toxins may alter channel gating. For example, the blue green algal toxins, aplysiatoxin, and lyngbyatoxin bind to and activate protein kinase C in a manner similar to phorbol esters (73). They also stimulate arachidonic acid metabolism (74). The coral toxin, palytoxin, also stimulates arachidonic acid breakdown albeit by an unknown mechanism (74) and affects other biochemical activities of the cell (see chapters by Fujiki et al., Wattenberg et al., and Levine et al., this volume). 

Lyngbyatoxin A Debromoaplysiatoxin Aplysiatoxin Bromoaplysiatoxin Dibromoaplysiatoxin Oscillatoxin A Anhydrodebromo-aplysiatoxin Palytoxin Okadaic acid TPA... 

A, aplysiatoxin, or palytoxin. Therefore, we proposed that okadaic acid binds to its own receptor and induces various biological effects, including tumor promoting activity, through this receptor (27). We are now investigating the nature of its receptor. 

Aplysin has marked effects in mammalian tissue and produces hypotension, bradycardia, neuromuscular paralysis, and contracture of intestinal smooth muscle (85). Aplysiatoxin causes an elevation in blood pressure resistant to adrenoceptor blockade (86). 

Of particular interest is Lyngbya majusculata which has been the subject of extensive studies. Interest in this species was first spurred by its ability to induce a dermatitis-like condition in swimmers ( swimmers itch ) which was traced to potent inflammatory, blister-producing and tumor promoting compounds such as aplysiatoxin, debromoaplysiatoxin and lyngbiatoxin... 

Debromoaplysiatoxin and aplysiatoxin were first isolated from the midgut gland of the sea hare Stylocheilus longicauda by Kato and Scheuer in 1974 (4). The two toxins were accompanied by the... 

X-ray structural data are available for TPA (35) and dihydro-teleocidin B (36-37), but only the absolute stereochemistry of TPA is known. As mentioned above the structure of aplysiatoxin has been solved by X-ray crystallography and its absolute stereochemistry has been determined from other data (10). These three tumor promoters, which represent three distinct classes of natural products, appear to have common structural features that enable it to bind to the same membrane receptors. 

Cross-cyclization of epoxides with homoallylic amines is an easy way to access tetrahydropyran moieties, which form the core structure of many biologically important natural products such as avermectins, aplysiatoxin, oscillatoxins, latrunculins, talaromycins, acutiphycins, and apicularens. Even though many methods are available for the synthesis of this moiety [14—24], its importance and wide applicability demands further methods. 

The previously known and notorious aplysiatoxin (a cause of swimmer s itch ) (7) is a protein kinase C inhibitor and has been the object of a structure-activity study (1582). The causative agents of a red alga Gracilaria coronopifolia poisoning... 

Knust H, Hoffmann RW (2003) Synthesis and Conformational Analysis of Macrocyclic Dilactones Mimicking the Pharmacophore of Aplysiatoxin. Helv Chim Acta 86 1871... 

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