Synthesis of antimicrofilament marine macrolides: synthesis and configurational assignment of a C5-C16 degradation fragment of reidispongiolide A.
Reidispongiolide A is a representative member of the sphinxolide/reidispongiolide group of cytotoxic 26-membered macrolides of marine origin. By interacting with actin in the cell cytoskeleton, the reidispongiolides and sphinxolides are potent microfilament destabilizing agents that represent a promising mechanism of action for developing novel anticancer drugs. An aldol-based synthesis of a library of diastereomers of C(8)-C(16) and C(5)-C(16) fragments and detailed NMR comparison with a reported degradation fragment enabled a configurational assignment for a major part of the reidispongiolide macrocyclic core, thus setting a solid foundation for ongoing synthetic efforts.
Paterson
Ian
I
University Chemical Laboratory, Lensfield Road, Cambridge CB2 1EW, United Kingdom. ip100@cam.ac.uk
Britton
Robert
R
Ashton
Kate
K
Knust
Henner
H
Stafford
Jonathan
J
D008841:Actin Cytoskeleton / Q000187:drug effects; D002625:Chemistry, Organic / Q000379:methods; D007659:Ketones / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D008386:Marine Biology; D008968:Molecular Conformation; D019906:Nuclear Magnetic Resonance, Biomolecular; D013237:Stereoisomerism
D007659:Ketones; D018942:Macrolides; C476919:reidispongiolide A