SYNTHESIS OF A 16-TRIAZOLE PHORBOXAZOLE A ANALOG VIA INTRAMOLECULAR TRIAZOLE FORMATION

摘要

The intramolecular formation of a triazole using a Cu(I)-catalyzed Huisgen [3+2]-cycloaddition between an organic azide and terminal alkyne enabled the preparation of a C16-C18 triazole analog of phorboxazole A.Phorboxazole A (1,Figure 1) and its C13 epimer are natural products isolated from Indian Ocean marine sponges Phorbas sp and Raspailia sp.With a mean GI50< 1.6 nM against the NCI panel of 60 tumor cell lines,phorboxazoles are among the most potent cytostatic agents discovered.