Total synthesis and biological evaluation of ustiloxin natural products and two analogs.
Synthetic investigations of ustiloxin natural products are described. The first total synthesis of ustiloxin F was completed in 15 steps via ethynyl aziridine ring-opening by a phenol derivative. The results of biological tests of synthetic ustiloxins D and F, and two analogs, O-Me-ustiloxin D and 6-Ile-ustiloxin, demonstrated that the free hydroxyl group ortho to the ether linkage is critical for activity and variations at the Val/Ala site produce changes in the biological activity suggesting the need for further perturbations at this site to more extensively study the tubulin binding.
Li
Pixu
P
Department of Chemistry, University of Pennsylvania, 231 S. 34th Street, Philadelphia, PA 19104, USA.
Evans
Cory D
CD
Forbeck
Erin M
EM
Park
Haengsoon
H
Bai
Ruoli
R
Hamel
Ernest
E
Joullié
M M
MM
D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D009183:Mycotoxins / Q000737:chemistry; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014404:Tubulin / Q000378:metabolism; D009842:Oligopeptides
D001688:Biological Products; D009183:Mycotoxins; D010456:Peptides, Cyclic; D014404:Tubulin; C112875:ustiloxin F; C089079:ustiloxin D; C035753:phomopsin; D009842:Oligopeptides