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The disecosteroid natural product gibbosterol A-which has a 14/5-bicyclic framework, a high oxidation state, and a twisted -9,11-epoxy motif-is the first water-soluble 5,10:8,9-disecosteroid. Herein, we report a bioinspired two-phase synthesis of this natural product in only 15 steps from inexpensive ergosterol. In the first (isomerase) phase, the core bicyclic framework is rapidly installed by the skeletal reorganization of ergosterol endoperoxide via a ruthenium-catalyzed dual C-C bond fragmentation. In the second (oxidase) phase, chemoselective, regioselective, and stereoselective redox transformations precisely introduce the requisite oxygenated functional groups. This work demonstrates that the ingenious two-phase synthesis logic that has been applied to terpenes is also a powerful strategy for steroid synthesis.