Kato Y, Ogawa Y, Imada T, Iwasaki S, Shimazaki N, Kobayashi T, Komai T
Institute of Applied Microbiology, University of Tokyo, Japan.
J Antibiot (Tokyo). 1991 Jan;44(1):66-75. doi: 10.7164/antibiotics.44.66.
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 Wittig reaction products 7-2, and of 20-O-acylates 13-21 were prepared and their anti-tubulin activity and cytotoxicity were determined. An aryl azide derivative 23 was synthesized as a photoaffinity analogue.
