In 1993, Schreiber and his co-workers reported the first total synthesis of the unnatural antipode (-)-discodermolide and determined the absolute stereochemistry of the natural product. The Schreiber team recognized three fragments of roughly equal complexity that are separated by olefinic units in discodermolide.  The two starting materials, homoallylic alcohols, are both readily derived from 3-hydroxy-2-methylpropionate.
The trisubstituted (Z)-alkene of first fragment was generated by using the Still-Gennari reagent. Gilbert's reagent was then used to homologate it to an acetylene. Goekjian and Kishi method was then used to get the desired fragment, iodoacetylene. The same homoallylic alcohol was converted to diol in four steps. After oxidation to keto-aldehyde, it was homololated to dienes by a palladium-catalyzed coupling with vinylzinc bromide to generated the second fragment.  The six-membered ring subunit was transformed from an acetal, which was obtained by an intramolecular 1,4-addition of a presumed hemiacetal intermediate.
The Schreiber team found that the NiCl and CrCl promoted addition of alkynyl iodide to aldehyde effectively. The reaction provides a 2:1 mixture of desired product and its isomer. However, the undesired isomer can be recycled to the desired epimer in three steps, including Swern oxidation and Corey's asymmetric reduction. Pd catalyzed partial hydrogenation of the alkyne to establish the Z-configuration at C(8)–C(9). The pivaloyloxy group was then converted to a bromide for the final coupling. A stereoselective enolate alkylation between the allylic bromide with the lithium enolate derived from the second fragment provided a 3:1 mixture of isomers and completed the backbone assembly of (-)-discodermolide. During the final conversion, the NaBH reduction of ketone provided a separable 2.5:1 mixture of isomers. The Schreiber synthesis of (-)-discodermolide has an overall yield of 3.2% with a longest linear sequence of 24 steps and 36 total steps. In 1996, the Schreiber group published the total synthesis of natural discodermolide with similar synthetic strategy (4.3% overall yield, 36 steps, 24 steps longest linear sequence.