Two syntheses of the C(7)–C(16)-fragment 41 of epothilone D 2 were developed that were based on tin(IV) bromide mediated reactions of 5,6-difunctionalised hex-2-enylstannanes with aldehydes. In the first synthesis, (5S)-6-tert-butyldimethylsilyloxy-5-hydroxy-2-methylhex-2-enyl(tributyl)stannane 20 was reacted with (E)-but-2-enal to give (2S,7R,4Z,8E)-1-tert-butyldimethylsilyloxy-5-methyldeca-4,...

[reaction: see text] A short synthesis of epothilone B and D is reported. The key step for generating the C12-13-trisubstituted Z-double bond uses a ring-closing metathesis reaction of a disiloxane to form a nine-membered silicon-tethered ring.

Previous work has shown that laulimalide, a sponge-derived natural product, resembles paclitaxel in enhancing tubulin assembly and in its effects on cellular microtubules. The two compounds, however, seem to have distinct binding sites on tubulin polymer. Nearly equimolar amounts of tubulin, laulimalide, and paclitaxel are recovered from microtubules formed with both drugs. In the present study...

Tumor resistance to chemotherapeutic agents ultimately leads to treatment failure in the majority of cancer patients. The identification of new agents that are less susceptible to mechanisms of tumor resistance could, therefore, bring significant clinical benefits to patients with advanced cancer. One new drug class of great interest in this respect is the epothilones and their analogues, which...

background: tubulin protein being the fundamental unit of microtubules is actively involved in cell division thus making them a potential anti-cancer drug target. in spite of many reported drugs against tubulin, few of them have started developing resistance in human β-tubulin due to amino acid substitutions. methods: in this study we generated three mutants (f270v, a364t and q292e) using model...

The progress in first-line chemotherapy in non-small cell lung cancer with efficient and often well-tolerated combinations has progressively led to the proposal of second-line chemotherapy for the patients. Docetaxel provides significantly enhanced survival compared with palliative treatments. Various phase II studies with vinorelbine, gemcitabine and paclitaxel have been reported. Pemetrexed h...