Studies on macrocyclic lactone antibiotics. XIII. Anti-tubulin 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 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.
Kato
Y
Y
Institute of Applied Microbiology, University of Tokyo, Japan.
Ogawa
Y
Y
Imada
T
T
Iwasaki
S
S
Shimazaki
N
N
Kobayashi
T
T
Komai
T
T
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D007536:Isomerism; D007783:Lactones / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D007941:Leukemia P388 / Q000188:drug therapy*; D018942:Macrolides; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D050257:Tubulin Modulators; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D007783:Lactones; D018942:Macrolides; D050257:Tubulin Modulators; C041443:rhizoxin