Reaction Steps
Taxol-2'-MPT (methylpyridinium tosylate) was synthesized according to the method of T. Mukaiyama, Angewandte Chemie 1979, 18(18), 707-808. Taxol (10 mg, 0.012 mM), from NaPro Biochemicals, Boulder Colo., USA, was dried by azeotropic distillation with toluene (2×1.0 mL) and then dissolved in methylene chloride (0.4 mL) and treated sequentially under an atmosphere of dry argon, with freshly distilled triethylamine (5 microL, 0.04 mM, 3 equivalents) and 2-fluoro-1-methylpyridinium tosylate (5 mg, 0.018 mM, 1.5 equivalents) Aldrich Chemicals, and allowed to stir at ambient temperature for 30 minutes. The clear colorless solution rapidly turned to a clear pale yellow. The course of the reaction was monitored through thin layer chromatography (TLC) (E. Merck RP-18 silica, 65 tetrahydrofuran:35 water, UV/phosphomolybdic acid) and after thirty minutes of stirring at ambient temperature, judged complete as no taxol remained and only one compound was apparent by TLC (Rf 0.8). Purification via reverse phase high pressure liquid chromatography (HPLC) (C18 column, 1 mM NH4OAc pH 6.5 buffer/methanol gradient, 1.5 mL/min. UV) to give, after removal of solvent in vaccuo, pure taxol-2'-MPT (2) (12 mg, 93% yield) as a white amorphous solid. All spectroscopic data (1H NMR and HRMS) were in accord with the structure assigned to taxol-2'-MPT. 1H NMR (CDCl3, 125 MHz) δ: 1.055 (s, 3H, C17-H), 1.083 (s, 3H, C19-H), 1.724 (s, 3H, C19-H), 1.858 (m, 1H, C6-βH), 1.913 (s, 3H, CH3 -Ph), 2.193 (s, 3H, C10-OC(O)CH3), 2.514 (m, 1H, C6-aH), 3.663 (d, 1H, J=7.0 Hz, C3-H), 4.110 (d, 1H, J=8.5, C20-aH, A of AB), 4.133 (s, 3H, N--CH3), 4.230 (d, 1H, J=8.5, C20-aH, B of AB), 4.315 (dd, 1H, J=8.7, 10.7, C7-H), 4.901 (dd, 1H, J=1.0, 7.7, C5-H), 5.501 (d, 1H, C2-H, J=7.0), 5.702 (bt, 1H, C2'-H, J=8.0), 5.951 (dd, 1H, C13-H, J=1.0, 8.0), 6.120 (bd, 1H, C3'-H, J=10.0), 6.181 (s, 1H, C10-H) 7.702 (t, 1H, N--H, J=7.5), 7.33-7.45 (m, 8H, Ar--H), 7.56-7.62 (m, 4H, Ar--H), 7.56-7.62 (m, 4H, Ar--H), 7.68-7.75 (m, 4H, Ar--H), 8.00-8.05 (m, 1H Ar--H), 8.23-8.28 (m, 1H, Pyr-H), 8.41 (m, 1H, Pyr-H). IR (neat, KCl plate) cm-1 : 3640-3120 (bm), 3030-2870 (bm), 2320 (m), 1720 (s), 1630 (m), 1560 (m), 1500 (m), 1360 (s), 1160 (m), 1070 (m), 700 (m). UV/Vis (CHCl3) nm: 254, 280. FAB HRMS: calc for C53H57 O14N2 : 945.3810; found: 945.3810.
