Studies toward Taxuspine X, a potent multidrug-resistance reversing agent, via ring closing metathesis strategy

A pharmacophore modeling approach to design new taxol® mimics: towards the synthesis of potential anticancer and MDR-reversing agent

“…Table 1. Structural and biological properties of taxanes (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) and epothilones (15,16,(18)(19)(20)(21) used in this study location of paclitaxel binding site in the β subunit but lacked the resolution to exactly define the whole ligand conformation. As a consequence, not all the amino acid residues were well solved and paclitaxel was replaced by the X-ray structure of docetaxel.…”

“…19 Compounds 24 offers several points of disconnection and an interesting challenge for an original synthesis, since no many procedures for preparing this constrained 12 membered macrocycle have been reported in literature. 20 Moreover, the delivery of enantiomerically pure molecules was not our priority at the moment, as the biological data for these modified taxuspine-like compounds are yet not available. Thus in the retrosynthetic analysis of 24, after appropriate protections, removal of the Taxol ® 's phenylisoserine side chain 21 and deoxygenation at the C-13 position 22 afforded a naked carbocyclic core (25), which was further simplified, leading to models 28 and 29, more easily accessible for our preliminary studies via RCM-based macrocyclization reaction and useful to optimize the synthetic procedures, as outlined in Scheme 2.…”

Second Joint Italian – Swiss Meeting on Medicinal Chemistry (ITCHMC 2005) Modena, September 12-16, 2005

“…An elegant approach to simplified 12membered macroyclic compounds via ring closure metathesis was presented (Scheme 6) [46]. In particular, taxuspine X exhibits a remarkable multidrug resistance (MDR)-reversing activity.…”

Oxygenated verticillene derivatives from Bursera suntui

“…These metabolites have been isolated from diverse sources such as the conifer Sciadopitys verticillata (Karlsson et al, 1978), the yew trees Taxus canadensis (Zamir et al, 1995(Zamir et al, , 1998, T. cuspidata (Renzulli et al, 2004), T. chinensis (Fang et al, 1995), T. chinensis var. mairei (Shi et al, 1998), and T. mairei (Shi et al, 2005), as well as the soft corals Cespitularia hypotentaculata (Duh et al, 2002) and C. taeniata (Shen et al, 2005), antipodal structures have also been found in the liverworts Jackiella javanica and Jungermannia infusca (Nagashima et al, 1997(Nagashima et al, , 2005.…”