STUDIES ON MACROCYCLIC LACTONE ANTIBIOTICS .13. ANTITUBULIN ACTIVITY AND CYTOTOXICITY OF RHIZOXIN DERIVATIVES - SYNTHESIS OF A PHOTOAFFINITY DERIVATIVE

Chemical modification of the side chain in rhizoxin, a potent antimitotic agent, was attempted in order to study structure-activity relationships and also to devise a probe for photoaffinity labeling of tubulin. An OsO4/NaIO4 oxidation gave a nor-rhizoxin 20-al (5) which was converted to 20-ol (6) by a NaBH3CN reduction. Starting from these two compounds as key intermediates, a series of Witting reaction products 7 approximately 12, and of 20-OMICRON-acylates 13 approximately 21 were prepared and their anti-tubulin activity and cytotoxicity were determined. An aryl azide derivative 23 was synthesized as a photoaffinity analogue.