Source: Dissertation Abstracts International, Volume: 53-03, Section: B, page: 1363.

Adviser: Frederick E. Ziegler.

The total synthesis of the marine metabolites $(-)$-denticulatins A and B has been completed. The natural products exist in the hemiketal form of a bis-$\beta$-hydroxy ketone and differ only as epimers at the C$\sb$ carbon. Isolated from Siphonaria denticulata, an air-breathing mollusk found off the coast of New South Wales, Australia, the denticulatins exhibit ichthyotoxicity as their only known source of biological activity.

An application of the 3-methyl-$\gamma$-butyrolactone strategy was utilized for asymmetric stereocontrol along the polypropionate C$\sb1$-C$\sb9$ fragment. The other issue concerning the synthesis involved the question of which of three potential modes of hemiketalization would prevail under acid hydrolysis of the open-chain, protected form of the denticulatins.

With a protected trione as the target precursor, the approximately thirty-five step retrosynthesis relied on an aldol coupling between the C$\sb$-C$\sb$ (R)-ethyl ketone and the C$\sb1$-C$\sb9$ keto aldehyde. Stereospecific cyclization generated the respective denticulatins when mild hydrolysis conditions were used for the removal of a p-methoxybenzylidene ketal. The (R)-ketone was obtained through the Enders RAMP hydrazone procedure, and the keto aldehyde was prepared from a modification of the polypropionate methodology involving an Ireland ester enolate Claisen rearrangement. The latter technique required (S)-3-methyl-$\lambda$-butyrolactone and both enantiomers of 2-methyl-4(E)-hexen-3-ol.