New strategy for the synthesis of the taxane diterpenes: Formation of the A-ring and introduction of the C-1 hydroxyl group

Novel Base-Catalyzed Rearrangement of the Taxane Skeleton

“…Thus, the fragmentation of the C-1/C-15 bond had already been observed, under acidic conditions, in a baccatin VI derivative, 11 and a long-range hydride shift was reported in two synthetic taxane model compounds. 12,13 It is interesting to note that both the formation of a 13-cation in compounds of the 1,13-dihydroxy type and the formation of a 1-alcoholate in compounds of the 1-hydroxy-13-oxo type, result in the formation of cyclodecane derivatives of the 1,15-secotaxane type. Formation of a C-1 cation triggers instead the rearrangement to 11 (15 f 1) abeotaxanes (brevifoliol-type compounds).…”

“…CIMS were taken on a Finnigan-MAT 4610 quadrupole instrument. 1 H-and 13 C-NMR spectra were taken on a Bruker AM-500 spectrometer (500.14 and 125.77 MHz, respectively), with TMS as reference. Si gel 60 (70-230 mesh, Merck) was used for column chromatography.…”

“…To a solution of 4 (100 mg, 0.27 mmol) in anhydrous Me 2 CO (500 µL) 1 drop of H 2 SO 4 was added at 0 °C, and the reaction was kept at 4 °C for 24 h. The reaction was worked up by the addition of H 2 O (1 mL), neutralized with saturated NaHCO 3 , and extracted with EtOAc (3 × 1 mL). After removal of the solvent, the residue was purified by column chromatography (hexane-EtOAc 6:4 as eluent) to give 31 mg (31%) of 6 as a white powder: mp 246-248 °C; [R] 25 D -68°(c 0.4, MeOH); IR (KBr) 3432, 1688, 1300, 1075, 1038, 911 cm -1 ; 1 H NMR (500.14 MHz, CDCl 3 , TMS as reference) δ 5.58 (1H, br s, H-20a), 5.13 (1H, br s, H-20b), 5.13 (1H, d, J ) 7.0 Hz, 1-OH), 4.98 (1H, p, J ) 7.0 Hz, H-1), 4.67 (1H, s, H-10), 4.30 (1H, d, J ) 2.2 Hz, 5-OH), 4.12 (1H, br q, J ) 3.3 Hz, H-5), 3.99 (1H, t, J ) 5.9 Hz, H-2), 3.36 (1H, d, J ) 5.9 Hz, H-3), 2.64 (1H, br q, J ) 7.0 Hz, H-12), 2.53 (1H, m, H-7β), 2.27 (1H, dd, J ) 11.5, 6.6 Hz, H-14R), 1.95 (1H, dd, J ) 8.5, 11.5 Hz, H-14β), 1.75 (3H, br s, H-16), 1.73 (2H, m, H-6R,β), 1.69 (3H, s, H-17), 1.42 (3H, s, H-19), 1.12 (3H, d, J ) 7.0 Hz, H-18), 0.97 (1H, dt, J ) 3.3, 1.4 Hz, H-7R); 13 C-8), 40.1 (t, C-14), 39.4 (d, C-12), 31.5 (t, C-7), 28.8 (t, C-6), 22.9 (q, C-16), 20.1 (q, C-17), 14.2 (q, C-19), 12.9 (q, C-18).…”