532403-03-5Relevant articles and documents
Semisynthesis of 7-deoxypaclitaxel derivatives devoid of an oxetane D-ring, starting from taxine B
Beusker, Patrick H.,Veldhuis, Harald,Brinkhorst, Johan,Hetterscheid, Dennis G. H.,Feichter, Nicolas,Bugaut, Anthony,Scheeren, Hans W.
, p. 689 - 705 (2003)
Six 7-deoxypaclitaxel derivatives have been prepared from taxine B; they contribute to understanding of the effect of the oxetane D-ring in paclitaxel on the cytotoxic activity of paclitaxel. Three of these analogues each contain a double bond instead of a D-ring at the C-4 position, while two others each contain a three-membered ring in place of the oxetane ring. Both the C-4 double bond and the small D-ring in these paclitaxel derivatives were intended to act as substitutes for the paclitaxel oxetane D-ring and were expected to impose on the taxane skeleton and the pendant groups a kind of rigidity and conformation similar to that produced by the oxetane ring in paclitaxel. All the derivatives demonstrated considerably reduced in vitro cytotoxic activity - relative to paclitaxel - against a panel of seven well-characterized human tumor cell lines. The general picture coming out of the structure-activity relationships of the paclitaxel derivatives reported here is that the presence of an oxygen atom at a spatial position resembling that of the oxygen atom in the oxetane ring of paclitaxel is important if a paclitaxel derivative is to retain considerable cytotoxic activity. Wiley-VCH Verlag GmbH & Co, KGaA, 69451 Weinheim, Germany, 2003.
