Sterols in marine invertebrates. Part 57. Stereostructure, synthesis, and acid-catalysed isomerization of hebesterol—a biosynthetically significant cyclopropyl-containing marine sterol

Abstract

Three new cyclopropane-containing sterols hebesterol (11), petrostanol (8), and 23,24-dihydro-5α-calystanol (10) have been isolated from the sponge, Petrosia hebes, together with the principal sterol, petrosterol (7), and 21 known sterols. The structure elucidation of the new trace sterols was accomplished by spectroscopic methods and partial synthesis. Hebesterol (11) and its trans-diastereoisomers (31)–(33) have been synthesized and their acid-catalysed cyclopropane ring-opening studied. Each hebesterol isomer (11), (31)–(33) was correlated with the recently synthesized ficisterol isomers (5), (53), (56), and (58) of known absolute stereochemistry, thus leading to an unambiguous assignment of the absolute stereochemistry of hebesterol. The other products from the acid-catalysed isomerizations were characterized by spectroscopic methods, synthesis, and mechanistic considerations. Two of these products, (23R)-23-ethyldesmosterol (51) and (23S)-23-ethyldesmosterol (59), provided a relay to the absolute stereochemistry of the 23-ethylcholestanols, which had previously been synthesized without assignment of absolute stereochemistry. Hebesterol (11) is the key ‘missing link’ with the predicted stereochemistry in a proposed biosynthetic sequence encompassing the unusual marine sterols dihydrocalysterol (9), petrosterol (7), and ficisterol (5).