Synthesis and stereochemistry of the terminal spiroketal domain of the phosphatase inhibitor dinophysistoxin-2.
An expedient synthesis of both axially and equatorially C35 methyl substituted spiroketals representing the C28-C38 domain of the potent and selective protein serine/threonine phosphatase inhibitor dinophysistoxin-2 (DTX-2) was developed to enable comparative stereochemical analyses and a stereochemically correct total synthesis of DTX-2. Comparison of proton and carbon NMR data of the synthetic diastereomers with those published for DTX-2 indicates that DTX-2 possesses the (30S *,34R *,35S *)-relative configuration with an axial C35 methyl substituent.
Forsyth
Craig J
CJ
Department of Chemistry, The Ohio State University, 100 W. 18th Avenue, Columbus, OH 43210, USA. forsyth@chemistry.ohio-state.edu
Wang
Ce
C
D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008387:Marine Toxins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D019319:Okadaic Acid / Q000031:analogs & derivatives; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D011714:Pyrans / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism
D004791:Enzyme Inhibitors; D005663:Furans; D008387:Marine Toxins; D011714:Pyrans; D013141:Spiro Compounds; C520774:spiroketal; D019319:Okadaic Acid; D010744:Phosphoric Monoester Hydrolases; C076221:dinophysistoxin 2