Reversible protein phosphorylation, which is mediated by kinases and phosphatases, is a major control element of the cell. There is a diverse group of toxic natural products that inhibit certain phosphatases, thereby disrupting normal biochemical pathways. These toxins can be useful for dissecting the individual biochemical pathways associated with each of these enzymes. This Article describes the first total synthesis of one such toxin, the cyclic heptapeptide microcystin-LA. The synthesis features a convergent route that is amenable to analog preparation in the search for selective phosphatase inhibitors. A new route to the unusual amino acid Adda is described, which incorporates an efficient diastereoselective aspartate alkylation and diene synthesis via a Suzuki coupling reaction. This work also features an efficient preparation of an N-methylalanine containing peptide via a Horner−Emmons condensation and several difficult amino acid coupling reactions that relied heavily on Carpino's remarkable HATU reagent.