Shellfish poisons, structure

Figure 5.59 Molecular structures of the diarrhetic shellfish poisons (a) pectenotoxin-6 (PTX6) (b) okadaic acid (OA) (c) dinophysistoxin-1 (DTXl) (d) yessotoxin (YTX). Reprinted from J. Chromatogr., A, 943, Matrix effect and correction by standard addition in quantitative liquid chromatographic-mass spectrometric analysis of diarrhetic shellfish poisoning toxins , Ito, S. and Tsukada, K., 39-46, Copyright (2002), with permission from Elsevier Science.

This chapter deals with single crystal x-ray diffraction as a tool to study marine natural product structures. A brief introduction to the technique is given, and the structure determination of PbTX-1 (brevetoxin A), the most potent of the neurotoxic shellfish poisons produced by Ptychodiscus brevis in the Gulf of Mexico, is presented as an example. The absolute configuration of the brevetoxins is established via the single crystal x-ray diffraction analysis of a chiral 1,2-dioxolane derivative of PbTX-2 (brevetoxin B). 

Murata, M., Isolation and structural elucidation of the causative toxin of the diarrhetic shellfish poisoning, Bull. Jpn. Soc.Sci. Fish, 48, 549, 1982. 

Murata, M., Isolation and structure of yessotoxin, a novel polyether compound implicated in diarrhetic shellfish poisoning, Tet. Lett., 28, 5869, 1987. 

An interesting and important example of an animal poison is paralytic shellfish poison (PSP). This chemical, which is also known as saxitoxin and by several other names as well, is found in certain shellfish. But it is not produced by shellfish it is rather a metabolic product of certain marine microorganisms (Protista). These microorganisms are ingested by the shellfish as food, and their poison can remain behind in the shellfish s tissue. Paralytic shellfish poison is not a protein, but a highly complex organic chemical of most unusual molecular structure. 

Cyanobacterial toxins (both marine and freshwater) are functionally and chemically a diverse group of secondary chemicals. They show structure and function similarities to higher plant and algal toxins. Of particular importance to this publication is the production of toxins which appear to be identical with saxitoxin and neosaxitoxin. Since these are the primary toxins involved in cases of paralytic shellfish poisons, these aphantoxins could be a source of PSP standards and the study of their production by Aphanizomenon can provide information on the biosynthesis of PSP s. The cyanobacteria toxins have not received extensive attention since they have fewer vectors by which they come in contact with humans. As freshwater supplies become more eutrophicated and as cyanobacteria are increasingly used as a source of single cell protein toxic cyanobacteria will have increased importance (39). The study of these cyanobacterial toxins can contribute to a better understanding of seafood poisons. 

Yessotoxin (214) is a polyether from the scallop Patinopecten yessoensis and has been implicated in diarrhetic shellfish poisoning (DSP). The structure and partial stereochemistry of yessotoxin were deduced from spectral data [219]. The relative stereochemistry of yessotoxin and the structures of two new analogues, 45-hydroxyyessotoxin (215) and 45,46,47-trinoryessotoxin (216) were also established [220]. The absolute stereochemistry of yessotoxin (214) was determined by NMR spectroscopy using a chiral anisotropic reagent [221]. The absolute configuration at C45 in 45-hydroxyyessotoxin (215), isolated from P. yessoensis, was determined by the use of a modified Mosher s method [222]. 

Chou, T., Haino, T., Kuramoto, M., and Uemura, D., Isolation and structure of pinnatoxin D, a new shellfish poison from the Okinawan bivalve Pinna muricata, Tetrahedron Lett., 37, 4027, 1996. 

Saxitoxin (32) is listed in Schedule 1 of the CWC. It is a polar, cationic, relatively low molecular mass toxin and is one of 18 structurally related neurotoxins collectively known as paralytic shellfish poisoning (PSP) toxins. Analogues are formed by addition of sulfate, A-sulfo and A-hydroxyl groups, and by decarbamylation. They block neuronal sodium channels, and thereby neurotransmission, death resulting from respiratory paralysis. Saxitoxin is produced by dinoflagellate species (and by some freshwater cyanobacteria), and accumulates in shellfish. The cationic nature of saxitoxin makes capillary electrophoresis combined with... 

In 1995, a report of human illness with diarrhetic shellfish poisoning (DSP)-like symptoms in the Netherlands was eventually found to result from the consumption of poisoned mussels (Mytilus edulis) harvested from Killary Harbour, Ireland (McMahon 1996). Yasumoto, Satake, and co-workers eventually isolated and proposed a stracture for the causative agent of this condition azaspiracid-1 (la. Fig. 16.1). The unique polyether stracture of azaspiracid-1 (la) is characterized by several spiro-cyclic systems, including an azaspiro ring fused to a 2,9-dioxabicyclo[3.3.1]nonane system and a terminal carboxylic acid. In total, there are nine rings and twenty stereogenic centers within the structure proposed by Yasumoto and co-workers in 1998 (Satake 1998). This stracture was based primarily on NMR spectroscopic data and did not include absolute stereochemistry, nor did it specify relative stereochemistry between the ABCDE and FGHI domains. 

The consumption of shellfish (scallops and mussels) harvested during late spring to early summer fiom the northeastern region of Japan quite often results in what is commonly known as diarrhetic shellfish poisoning. An initial chemical investigation of the toxic mussels resulted in the identification (86) of okadaic acid [108], dinophysistoxin 1 (DTXj) [109] and two toxins of unknown structures. In a later study (87), chemical structures of three new polyether toxins, dinophysistoxin- 3 (DTX3)[110], pectenotoxin-1 [111 ] and pectenotoxin-2 [112] were reported. 

Saxitoxin, the paralytic shellfish poison, has finally revealed its structure as (87) by X-ray crystallographic analysis of its ethyl hemiketal " and p-bromobenzene-sulphonate derivatives. C n.m.r. studies show that saxitoxin exists primarily as its ketone hydrate in aqueous solution. ... 

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