Yessotoxin

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.

Three classes of polyethers, okadaic acid derivatives, pectenotoxins, and yessotoxin were isolated from bivalves in connection with diarrhetic shellfish poisoning. The etiology of the toxins, toxicological properties, and determination methods are described. 

Microalgae produce many potent natural products in the form of complex polycyclic polyethers, a type of polyketide. The ladder-like polyether brevetoxin B (Fig. 1.8a) (Lin et al. 1981) is representative of a host of such toxins, which include cigua-toxin (Scheuer et al. 1967), yessotoxin (Murata et al. 1987), maitotoxin (Murata et al. 1993), gambieric acids (Murata et al. 1992), and azaspiracid (Satake et al. 1998). Brevetoxin B, one of the causitive agents of red tide poisoning, can be isolated from... 

The toxins responsible for DSP include a series of polyether molecules (including okadaic acid and six derivatives of dinophysistoxin), four pecteno-toxins (polyether lactones), and yessotoxins (including two sulfate esters that resemble brevetoxins) (Murata, 1982 Murata, 1987 Tachibana et al., 1981 Yasumoto, 1989). Diarrhetic shellfish poisons are produced primarily by dinoflagellates from the genera Dinophysis, although Prorocentrum lima also produces both okadaic acid and dinophysistoxin-1 (Heredia-Tapia et al., 2002). 

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

Terao, K., et al., Histopathological studies on experimental marine toxin poisoning - 5. The effects in mice of yessotoxin isolated from Patinopecten yessoensis and of a desulfated derivative, Toxicon, 28, 9, 1095, 1990. 

Eor the synthesis of the A-E ring segment of yessotoxin and adriatoxin by analogous methodology, see Kadota, I. Ueno, H. Yamamoto, Y. 

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]. 

Two analogues of yessotoxin, homoyessotoxin (217) and 45-hydroxyhomoyessotoxin (218) were isolated from the digestive glands of mussels from the Adriatic Sea. Their structures were determined by NMR spectroscopy and mass spectrometry [223]. Adriatoxin (219), a further yessotoxin analogue, was isolated from the digestive glands of the mussel... 

This chemistry features in a synthesis of the left hand fragment of yessotoxin and adriatoxin <02OL3943>. Assembly of the F-N ring component of gymnomycin A, involves a b-alkyl Suzuki-Miyaura coupling reaction <02OL1747>. 

A number of reports have appeared on the use of carbonyl-alkene additions to construct oxacyclic ring systems efficiently with high diastereoselectivity. Nakata showed that even the formation of seven-membered cyclic ethers using the transformation can be remarkably efficient and utilised the strategy to form the E ring of the polycyclic ether marine natural product yessotoxin (Scheme 5.34).64... 

Yessotoxin and its analogues are disulfonated polyether toxins reported from shellfish from different countries, but a new derivative lacking a 1-sulfated substituent, 1-desulfoyessotoxin (YTX with R =H), has been isolated from mussels from Norway <1998MI235>. Its ESI-MS spectrum showed that this compound is 102 Da smaller than YTX 17, implying that one of the sulfate esters in YTX was desulfonated. The NMR data of 1-desulfoyessotoxin are similar to that of YTX 17 except for the 1-methylenic protons where desulfonation occurred they are shifted to upheld by 0.49ppm and their chemical shifts (3.72 and 3.78ppm) are typical of hydroxymethyl protons. 

Numerous studies have been conducted with cultures of the marine dinoflagellate Protoceratium reticulatum not only to confirm the biogenetic origin of yessotoxin 17 and 45,46,47-trinoryessotoxin 20 <1997MI164, 1999MI147>, but also to isolate and assign the structure of known and new YTX analogues, such as 27 (a l-en-3-one isomer of... 

Alfonso A., de la Rosa, L.A., Vieytes, M.R., Yasumoto, T, and Botana, L.M. 2003. Yessotoxin, a novel phycotoxin, activates phosphodiesterase activity. Effect of yessotoxin on cAMP levels in human lymphocytes. Biochem Pharmacol 65, 193-208. 

Aasen, J., Samdal, I.A., Miles, C. O., Dahl, E., Briggs, L.R., and Aune, T. 2004. Yessotoxins in Norwegian blue mussels Mytilus edulis). uptake from Protocemtium reticulatum, metabolism and depuration. Toxicon 45, 265-272. 

Draisci, R., Lucentini, L, and Mascioni, A. 2000. Pectenotoxins and yessotoxins chemistry, toxicology, pharmacology, and analysis. In Seafood and Freshwater Toxins Pharmacology, Physiology, and Detection, ed. Botana, L.M. New York Marcel Dekker, Inc., 289-324. 

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