Structure spirolide

Pinnatoxins are the cyclic imines most closely related in structure to spirolides (Figure 26.4). They differ slightly in the polyether ring system (6-5-6) and in an additional bicyclic ether moiety in the macrocycle, which is absent in spirolides. Pinnatoxin variants differ in the length of their cyclohexenyl side chains pinnatoxin-A has just a Cl carboxylic group, the enantiomeric diastereoisomers pinnatoxin-B and -C possess a C2 entity consisting of a 2-amino acetic acid function, and pinnatoxin-D includes a C4 y-ketobutyric acid moiety. 

Spirolides consist of two structural types. Type A, comprising spirolides A, B, C, D, and their desmethyl variants, has a 6-5-5 polyether ring system and a hydroxy group at the 10 position. Spirolides A and B have one methyl group on the cyclo-imine ring, whereas spirolides C and D are doubly methylated. Spirolides A and C are 2,3-unsaturated, whereas spiroUdes B andD are the saturated counterparts. The Type G spirolides, in contrast to Type A, have a 6-6-5 polyether ring system and a hydroxy group shifted from the 10 to the 17 position. 

FIGURE 26.8 Structural variants of spirolides found among marine dinoflagellates... 

All of the cyclic imine toxins (except spiro-prorocentrimine) may be structurally classihed as macrocyclic polyethers. Although the elucidation of biosynthetic pathways for polyether dino-flagellates toxins is limited to the ladder frame polyether brevetoxins [40], the linear polyether dinophysistoxins DTX4 and DTX5 [11,41] and the macrocyclic imine des-methyl spirolide C... 

In the early 1990s, routine bioassays detected the presence of a fast-acting toxin in extracts of shellfish from sites along the southeastern coast of Nova Scotia, Canada [11]. Two new toxins of the cyclic imine group, named spirolide B and spirolide D, were isolated from the viscera of scallops (Placopecten magellanicus) and mussels (M. edulis) and their structures determined [12]. Subsequently, spirolides A, C, E, and F were described, along with 13-desmethyl spirolide C [13,14]. 

Among the spirolide derivatives thathave been studied in detail (spirolide C, desmethyl spirolide C and 20-methyl spirolide G), there is little difference in acute toxicity, either by injection or by oral administration. In pinnatoxin and pteriatoxin derivatives, however, large differences in toxicity are seen among compounds of different structure. Pinnatoxins A-C and pteriatoxins A-C differ only in the nature of the substituent at position 33. hi both, compounds B and C are stereoisomers. Pinnatoxin A, which has a carboxyl group at C-33, is approximately 14 times less toxic than a mixture of pinnatoxins B and C, which have a glycine residue at this site. The situation with the pteriatoxins is even more remarkable. These compounds may be considered as derivatives of 3-(2-hydroxyethylthio)-... 

Sleno L., Chalmers M.J. and Volmer D.A. Structural study of spirolide marine toxins by mass spectrometry. Part 11. Mass spectrometric characterization of unknown spirolides and related compounds in a cultured phytoplankton extract, Anal. Bioanal. Chem. 378, 977, 2004. 

All spirolides A-I contain a y-lactone associated with a complex structure containing a cyclic imine with seven... 

Gueret, S.M. and Brimble, M.A. (2010) Spiroimine shellfish poisoning (SSP) and the spirolide family of shellfish toxins isolation, structure, biological activity and synthesis. Nat. Prod. Rep., 27, 1350-1366. 

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