(+)-Diplopyrone is an optically active phytotoxin isolated from Diploda mutila, an endophytic fungus considered one of the main causes of cork oak (Quercus suber L.) decline. The focus of this research was a synthetic approach to enantiomeric (-)-diplopyrone from commercially available tri-O-acetyl-D-galactal. The main strategy in this project was the formation of the C-glycoside linkage.

We were unable to create a C-glycoside via the samarium-Barbier coupling. We prepared a C-1 nitrile via the Ferrier rearrangement in good yield, but were unable to transform it into the hydroxyethyl group found on (-)-diplopyrone. Initial attempts to convert the nitrile to an aldehyde or ketone using Grignard or hydride reagents failed.

We also sought to form a lactone using ring closing metathesis, but were unable to form the vinyl RCM precursor. We were able to functionalize the C-6 position to an aldehyde, but attempts to form a vinyl group via the Wittig, Tebbe, or Peterson reactions failed.

We discovered that the nitrile spontaneously eliminates under basic conditions through an E₂' mechanism to form a conjugated system. A compound was synthesized that should be unable to react via this mechanism, allowing basic reagents to be used without the formation of side products.

We were able to functionalize the C-4 and C-6 positions of the molecule. The C-6 aldehyde was converted to a cis α,β-unsaturated ester via a Z-selective Wittig olefination using a stabilized ylide in methanol. The ester was cyclized to a lactone under acidic conditions to form the nitrile analog of (-)-diplopyrone.