MARINE CHEMISTRY WITH SPECIAL EMPHASIS ON STEROIDS

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Work in our and other laboratories has shown that lower marine animals are a rich source of structurally unusual sterols, which have no counterpart in terrestrial sources. On the other hand, these sterols have unusual side chains - frequently much more branched - than those found in cholesterol and its congeners. Work will be performed to elucidate the mechanism of biosynthesis of these sterols and to determine their origin in the complex host-symbiont relationships of these marine animals by isolation and laboratory culture of the symbionts. The biological function of these unique sterols is probably related to membrane function and extensive work is envisaged on isolating and structurally identifying the phospholipids from such marine animals, which also seem to have unique fatty acids. Model membranes will be prepared using these unusual phospholipids and then compare the role of these marine sterols with that of cholesterol in such model membranes. On the other hand, some of the marine sterols also possess unusual nuclei and their biological role also needs elucidation. Here again, a membrane function can be envisaged, but in this instance it should reflect itself in unusual head group (rather than fatty acid) constituents of these phospholipids. Among the unusual nuclei, a striking one is the 19-nor-ring A system, which has never been encountered in nature, even though it constitutes the key functionality in all synthetic oral contraceptives. Another example are the A-nor sterols, in which ring A is five-membered. We hope to shed light on the biological function of these unique sterol types. In summary, well over 100 new sterols have been isolated during the past few years from marine sources and this veritable explosion seems to continue unabated. Among them are a group of sterols with cyclopropane rings in the side chain and we believe that they may represent an intermediate in an alternate mode of biomethylation, which would be of fundamental interest. Biosynthetic studies are envisaged with unicellular organisms capable of synthesizing such sterols.