D-ring substituted rhazinilam analogues: semisynthesis and evaluation of antitubulin activity.
Novel (-)- and (+)-rhazinilam derivatives substituted on the D-ring (compounds 3, 4, 5 and 6) have been prepared from (+)-vincadifformine 7 and (-)-tabersonine and evaluated against the disassembly of microtubules into tubulin. Along with this study, a reproducible 'one pot' semisynthesis of (-)-rhazinilam 1 from (+)-1,2-didehydroaspidospermidine 2 was performed allowing the easy preparation of these new compounds.
Dupont
C
C
Institut de Chimie des Substances Naturelles, Centre National de la Recherche Scientifique, Gif-sur-Yvette, France.
Guénard
D
D
Tchertanov
L
L
Thoret
S
S
Guéritte
F
F
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D018360:Crystallography, X-Ray; D066298:In Vitro Techniques; D007212:Indolizines; D007769:Lactams; D009682:Magnetic Resonance Spectroscopy; D008870:Microtubules / Q000187:drug effects; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D050257:Tubulin Modulators
D000470:Alkaloids; D007212:Indolizines; D007769:Lactams; D050257:Tubulin Modulators; C009170:rhazinilam