Two polar lipid-soluble macrocycles 1 and 2, containing a spiro-linked tricyclic ether ring system and an unusual seven-membered spiro-linked cyclic iminium moiety, have been isolated from the digestive glands of mussels (Mytilus edulis) and scallops (Placopecten magellanicus).During chemical investigations of polar bioactive molecules from microalgae and shellfish,' we isolated from the digestive glands of both mussels (Mytilus edulis) and scallops (Placopecten magellanicus), a family of novel macrocycles which we have named spirolides A-D. Here we report the structural elucidation of the two major components, spirolides B and D.Spirolide B 1 and D 2 (Fig. 1) were purified from methanolic extracts of frozen digestive glands of shellfish collected from sites along the eastern shore of Nova Scotia.? High resolution LSIMS determined the molecular formulae for 1 and 2 to be C42H63N07 (MH+ 694.4651, 6 4.5) and C ~~H G ~N O ~

Three additional marine toxins, spirolides A (1), C (3), and 13-desmethyl-C (7), were isolated from contaminated scallops and phytoplankton collections obtained from a Nova Scotian aquaculture site, as well as from batch cultures of the dinoflagellate Alexandrium ostenfeldii obtained as a single-cell isolate from these phytoplankton assemblages. The structures of these new spirolide derivatives, characterized by mass spectrometry and NMR, indicate a close relationship with spirolides B (2) and D (4) isolated previously from contaminated shellfish in the same area. All of these compounds display "fast-acting" toxicity in the traditional bioassay used for monitoring shellfish, and this is related to the presence of a cyclic imine function in all these compounds. Those spirolides containing a vicinal dimethyl group in the seven-membered ring are resistant to oxalic acid hydrolysis, whereas those that do not are readily hydrolyzed. These observations suggest that the extra methyl group on the seven-membered imine ring of 3, 4, and 7 appears to block the process of imine hydrolysis perhaps by stereochemical interference.

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