In 1999, Smith and his co-workers reported the first gram-scale synthesis of (+)-discodermolide, which make the development of (+)-discodermolide as a potential chemotherapeutic agent possible. This synthetic route was licensed to Novartis Pharmaceuticals. One of the major improvements was that no purification was required in the first four steps of the five-step sequence towards the common precursor as the intermediate, aldol adduct, is a crystalline solid. A chelation-controlled Mukaiyama-aldol reaction was used to set the stereogenicity at C(5) of the lactone fragment.