402827-33-2Relevant academic research and scientific papers
Synthesis of novel simplified sarcodictyin/eleutherobin analogs with potent microtubule-stabilizing activity, using ring closing metathesis as the key-step
Beumer, Raphael,Bayón, Pau,Bugada, Piergiuliano,Ducki, Sylvie,Mongelli, Nicola,Sirtori, Federico Riccardi,Telser, Joachim,Gennari, Cesare
, p. 8803 - 8820 (2007/10/03)
The synthesis of a number of novel simplified eleutheside analogs with potent tubulin-assembling and microtubule-stabilizing properties is described, using ring closing metathesis as the key-step for obtaining the 6-10 fused bicyclic ring system. The RCM precursors were synthesized starting from aldehyde 3 [prepared in 6 steps on a multigram scale from R-(-)-carvone in 30% overall yield] via multiple stereoselective Brown allylations. Second generation RCM catalyst 13 gave the desired ring closed 10-membered carbocycles as single Z stereoisomers in good yields. The RCM stereochemical course (100% Z) likely reflects thermodynamic control. The crucial role of the protecting groups of the homoallylic and allylic substituents for the efficiency of the RCM reactions is discussed. These simplified analogs of the natural product (lacking inter alia the C-4/C-7 ether bridge) retain potent microtubule-stabilizing activity. However, the cytotoxicity tests did not parallel the potent tubulin-assembling and microtubule-stabilizing properties: limited cytotoxicity was observed against three common tumor cell lines (human ovarian carcinoma and human colon carcinoma cell lines, IC50 in the μM range given in Table 2), three orders of magnitude less than paclitaxel (IC50 in the nM range).
Synthesis of a simplified sarcodictyin analogue which retains microtubule stabilising properties
Telser, Joachim,Beumer, Raphael,Bell, Andrew A.,Ceccarelli, Simona M.,Monti, Diego,Gennari, Cesare
, p. 9187 - 9190 (2007/10/03)
A strategy featuring ring-closing metathesis as key reaction is applied to the synthesis of the sarcodictyin analogue 15. The precursor diene is accessed via a brief and efficient protocol, employing multiple stereoselective allylations. Simplified analog
