Total Synthesis Highlights

83. Synthesis of (+)-Phomactin A
The diterpene (+)-Phomactin A 4 is an antagonist of platelet activating factor. The preparation of 4
recently reported (J. Am. Chem. Soc. 2003, 125, 1712.) by Randall Halcomb of the University of
Colorado elegantly illustrates the use of readily-available natural products as starting materials for
natural product synthesis.
The synthetic plan called for a late-stage intramolecular reductive coupling of the iododiene 3 to
establish the macrocyclic ring of 4. The iododiene 3 was to be assembled by condensation of the
highly-substituted cyclohexene 1 with the aldehyde 2.
The aldehyde 2 was prepared from the inexpensive geraniol ether 5. Selective ozonolysis followed
by Wittig homologation gave the bromodiene, which was converted via dehydrobromination and
alkylation to the alkyne 6. Regioselective hydridozirconation followed by iodination of the C-Zr
bond gave the alkenyl iodide 7 with high geometric control. The two stereogenic centers of 2 were
then established by Sharpless asymmetric epoxidation.
The preparation of the cyclohexene 1 began with pulegone 8, available commercially in high
enantiomeric purity. Methylation followed by retro aldol condensation to remove the unwanted
isopropylidene group gave 2,3-dimethylcyclohexanone, which on
bromination-dehydrobromination gave 9. Vinylation followed by alkylative enone transposition