Taxol, isolated from the bark of Taxus breVifolia in the late 1960s, 1 and its semisynthetic Taxotere congener 2 have become the drugs of choice for the treatment of ovarian and breast cancer. 3 The availability of active simplified analogues would facilitate shortened synthetic strategies and potentially bypass neurotoxicity 4 and multidrug resistance. 5 The design of such compounds is hampered by an incomplete understanding of Taxol’s conformation in the bioactive form. Numerous studies have sought to deduce the drug’s three-dimensional state in solution by NMR spectroscopy combined with force-field guided conformational analysis. In both polar and nonpolar solvents, rotamers exhibit hydrophobic collapse 6 between the flexible C-2, C-4, and C-13 side chains, accompanied by variable H2′-C-C-H3′ torsional angles (Table 1). 7,8 Each of the conformational extremes has been proposed as a candidate for the Taxol topology bound to microtubules. 7d,g-j,8b-d