Supporting Information Synthesis, Modeling and Anti-Tubulin Activity of a D-Seco Paclitaxel Analog Luciano Barboni, †* Guido Giarlo, † Massimo Ricciutelli, † Roberto Ballini, † Gunda I. Georg, ‡* David G. VanderVelde, ‡ Richard H. Himes, § Minmin Wang, ∞ Ami Lakdawala, ∞ and James P. Snyder ∞* Dipartimento di Scienze Chimiche, Università di Camerino, 62032 Camerino (MC), Italy, Department of Medicinal Chemistry, University of Kansas, Drug Discovery Program, Higuchi Biosciences Center, University of Kansas, and Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas 66045, and Department of Chemistry, Emory University, Atlanta, Georgia, 30322 General Methods S1 Preparation of Compound 5 S1 Preparation of Compound 6 S2 Preparation of Compound 7 S2 Preparation of Compound 8 S2 Preparation of Compound 1 S3 Experimental: General Methods. NMR spectra were taken on Bruker Avance 400 or Varian VXR 300 spectrometers. Cytotoxicity and tubulin binding were carried out according to established protocols. 1 Commercially available reagents and solvents were used without further purification. All anhydrous reactions were performed under a positive pressure of nitrogen. CH 2 Cl 2 was dried by distillation from CaH 2 , and THF by distillation from Na- benzophenone. Solvent evaporation was done under reduced pressure. Column chromatography was carried out with silica gel as the stationary phase. Preparation of compound 5: To a stirred solution of compound 4 (655 mg, 0.611 mmol) in anhydrous CH 2 Cl 2 at ambient temperature, Bu t 4 NI (1.830 mmol, 675 mg) and MgBr 2 ·Et 2 O (0.775 mmol, 200 mg) were added. The reaction mixture was stirred under N 2 at rt for 5 h (monitored by TLC, hexane/EtOAc 4:1) then further Bu t 4 NI (0.542 mmol, 200 mg) and MgBr 2 ·Et 2 O (0.388 mmol, 100 mg) were added. After 3 h the reaction mixture was diluted with CH 2 Cl 2 and washed successively with water, 5% NaHCO 3 and brine. The organic phase was dried over anhydrous Na 2 SO 4 and evaporated to dryness. The crude product was purified by silica gel chromatography (hexane/EtOAc 85:15) to give compound 5 (638 mg, 87%) as an amorphous solid. 1 H NMR (CDCl 3 , 400 MHz): δ - 0.33 (s, 3H), -0.13 (s, 3H), 0.59 (q, J = 7.9 Hz, 6H), 0.80 (s, 9H), 0.94 (t, J = 7.9 Hz, 9H), 1.13 (s, 3H), 1.22 (s, 3H), 1.37 (s, 3H), 2.11 (m, 1H), 2.19 (s, 3H), 2.33 (m, 1H), 2.48 (dd, J = 15.7, 9.9 Hz, 1H), 2.50 (bs, 3H), 3.01 (dd, J = 15.7, 5.6 Hz, 1H), 3.85 (d, J = 10.8 Hz, 1H), 3.98 (d, J = 5.0 Hz, 1H), 4.18 (d, J = 10.8 Hz, 1H), 4.29 (s, 1H), 4.34 (d, J = 5.0 Hz, 1H), 4.57 (dd, J = 10.5, 3.8 Hz, 1H), 4.61 (d, J = 2.0 Hz, 1H), 5.15 (bs, 1H), 6.03 (m, 1H), 6.05 (bd, J = 8.6 Hz, 1H), 6.60 (s, 1H), 7.14 (d, J = 8.5 Hz, 1H), 7.26 (m, 2H), 7.34 (bt, J = 7.4 Hz, 2H), 7.47 (m, 3H), 7.52 (m, 1H), 7.80 (m, 2H); 13 C NMR (100 MHz, CDCl 3 ): δ -5.95, -5.58, 5.16, 6.76, 13.77, 14.38, 17.82, 18.22, 19.77, 20.77, 25.53, 26.37, 32.81, 39.05, 41.07, 43.88, 45.38, 55.62, 62.15, 71.02 (2C), 71.30, 75.17, 75.24, 82.08, S1