New highly active taxoids from 9β-Dihydrobaccatin-9,10-acetals

Synthesis and Structural Studies of 1‐Deoxybaccatin VI Derivatives

“…Those molecular formulas were also consistent with data from the 1 H and 13 C NMR spectra of 2 and 3. The comparison of the 1 H NMR spectra of 1 and 2 indicates that the two compounds are closely related but differ at C (13). The chemical shift of the C(13) methine proton shifted upfield to 4.57-4.59 (m) in 2 from 5.95 (t, J＝8.3 Hz) in 1, confirming that deacetylation had occurred at C(13).…”

“…12 More recently, Soga et al reported that 9β-dihydro-9,10-isopropylidene taxoids showed stronger activity than docetaxel against tumor cell lines whereas 9β-dihydrodocetaxel is less potent than docetaxel. 13 This indicates the effectiveness of the isopropylidene group at the 9,10-position of the taxane skeleton, increasing potency compared to free hydroxyl groups at the two positions. These interesting results have stimulated efforts to elucidate the mechanism of action.…”

“…Anticancer taxoids with high potency against drug-resistant cancer cells have been prepared based on these observations. 8 In contrast, structural modification in the southern region [C(2), C(4)] and the side chain [C (13)] can dramatically alter activity. 6 Recent studies on structural modifications of 1-deoxybaccatin VI 9 along with resulting conformational changes in our laboratory 10,11 revealed that removal of 4-acetyl or 2,4-diacyl moiety has a decisive impact on the conformation of ring A.…”

“…These derivatives contain a diversity of substituents external to ring and thus offer a broad view of flexibility in the tetracyclic ring system. 1 H NMR and 13 C NMR spectra were recorded on a Bruker DM-500MHz spectrometer at 500.134 MHz and 125.771 MHz, respectively, with TMS as an internal standard. HPLC analysis was performed on an Agilent 1100 series LC system connected to a G1322A vacuum degasser, a G1311A quaternary pump, a G1313A autosampler, a G1316A thermostatted column compartment, a G1314A variable wavelength detector and Agilent chemostation software.…”

A New Method for Synthesis of 7-Deoxytaxane Analogues by Hydrogenation of .DELTA.6,7-Taxane Derivatives.

“…14) On the other hand, our novel analogues, 9b-isomer, showed stronger activity against several tumor cell lines than did docetaxel. 10,15) Therefore, we applied this newly developed method to the synthesis of their 7-deoxy analogues. 9,10-O-Acetonide 9 10) was treated with triflic anhydride in CH 2 Cl 2 in the presence of DMAP, elimination of 7-O-triflate occurred to afford the 6,7-olefin 10.…”