Presented within are syntheses of the pladienolide B and FD-895 side-chains, as well as models of the essential ring-closing metathesis and Stille coupling that will be used to complete their total syntheses. Several analogs of the pladienolide B side-chain were also prepared in order to evaluate the scope of the methodology and to create a library of structures that could be used for stereochemical and SAR analyses.