496918-80-0Relevant academic research and scientific papers
Design, synthesis, and biological evaluation of novel C14-C3′BzN- linked macrocyclic taxoids
Sun, Liang,Geng, Xudong,Geney, Raphael,Li, Yuan,Simmerling, Carlos,Li, Zhong,Lauher, Joseph W.,Xia, Shujun,Horwitz, Susan B.,Veith, Jean M.,Pera, Paula,Bernacki, Ralph J.,Ojima, Iwao
scheme or table, p. 9584 - 9593 (2009/04/06)
(Figure Presented) Novel macrocyclic paclitaxel congeners were designed to mimic the bioactive conformation of paclitaxel. Computational analysis of the REDOR-Taxol structure revealed that this structure could be rigidified by connecting the C14 position of the baccatin moiety and the ortho position of C3′N-benzoyl group (C3′BzN), which are ca. 7.5 A apart, with a short linker (4-6 atoms). 7-TES-14β-allyloxybaccatin III and (3R,4S)-1-(2-alkenylbenzoyl)-β-lactams were selected as key components, and the Ojima-Holton coupling afforded the corresponding paclitaxel-dienes. The Ru-catalyzed ring-closing metathesis (RCM) of paclitaxel-dienes gave the designed 15- and 16-membered macrocyclic taxoids. However, the RCM reaction to form the designed 14-membered macrocyclic taxoid did not proceed as planned. Instead, the attempted RCM reaction led to the occurrence of an unprecedented novel Ru-catalyzed diene-coupling process, giving the corresponding 15-membered macrocyclic taxoid (SB-T-2054). The biological activities of the novel macrocyclic taxoids were evaluated by tumor cell growth inhibition (i.e., cytotoxicity) and tubulin-polymerization assays. Those assays revealed high sensitivity of cytotoxicity to subtle conformational changes. Among the novel macrocyclic taxoids evaluated, SB-T-2054 is the most active compound, which possesses virtually the same potency as that of paclitaxel. The result may also indicate that SB-T-2054 structure is an excellent mimic of the bioactive conformation of paclitaxel. Computational analysis for the observed structure-activity relationships is also performed and discussed.
14β-Hydroxy-10-deacetylbaccatin III as a convenient, alternative substrate for the improved synthesis of methoxylated second-generation taxanes
Barboni, Luciano,Giarlo, Guido,Ballini, Roberto,Fontana, Gabriele
, p. 5389 - 5391 (2007/10/03)
This article describes a new, convenient, improved synthesis of the 2-debenzoyl-2-m-methoxybenzoyl-7-triethylsilyl-13-oxo-14β-hydroxybaccatin III 1,14-carbonate, the key intermediate in the synthesis of two new second-generation antitumor taxanes.
Synthesis and evaluation of 14-nor-a-secotaxoids
Appendino, Giovanni,Belloro, Emanuela,Del Grosso, Erika,Minassi, Alberto,Bombardelli, Ezio
, p. 277 - 283 (2007/10/03)
A series of 14-nor-A-secotaxoids has been prepared from 10-deacetyl-14β-hydroxybaccatin III (3a) and some unexpected and new reactivity of the taxane system has been revealed. The observation that the final compounds were considerably less active than taxol and their 1,10-oxygen-bridged ana-logues shows that the 1,10-oxygen tether can partially compensate for the opening of ring A, and suggests that 14-norA-secotaxoids warrant further investigation as simplified taxol mimics. WILEY-VCH Verlag GmbH 2002.
