Intramolecular radical cyclization-ring-closing metathesis approach to fused polycyclic ethers. Convergent synthesis and conformational analysis of the (E)FGH ring system of ciguatoxin.
A convergent synthetic route to the (E)FGH ring system 4 of ciguatoxins, the causative toxins for ciguatera fish poisoning, has been developed. The synthesis features convergent coupling to form dioxane acetal, regioselective acetal cleavage by diethylaluminum phenylthiolate or diisobutylaluminum phenylselenolate followed by intramolecular radical cyclization to construct the oxepane ring G, and a ring-closing metathesis reaction to form the hexahydrooxonine ring F. The hexahydrooxonine ring F of tetracyclic model system 4 existed as a 5:1 equilibrium mixture of two conformers (UP and DOWN conformers), with the UP one predominating. This is the first illustration that reproduces the preference for the UP conformer over the DOWN one, which preference was observed for natural ciguatoxins.
Sasaki
Makoto
M
Department of Chemistry, Graduate School of Science, The University of Tokyo, and CREST, Japan Science and Technology Corporation (JST), Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. msasaki@chem.s.u-tokyo.ac.jp
Noguchi
Tetsuji
T
Tachibana
Kazuo
K
D000080:Acetals; D000438:Alcohols; D000475:Alkenes; D000480:Alkynes; D000818:Animals; D002384:Catalysis; D002625:Chemistry, Organic / Q000379:methods*; D002922:Ciguatoxins / Q000138:chemical synthesis / Q000737:chemistry*; D003500:Cyclization; D004524:Eels; D004988:Ethers, Cyclic / Q000737:chemistry*; D007783:Lactones; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D013237:Stereoisomerism
C466859:51-hydroxyciguatoxin 3C; D000080:Acetals; D000438:Alcohols; D000475:Alkenes; D000480:Alkynes; D004988:Ethers, Cyclic; D007783:Lactones; C466858:ciguatoxin 3C; D002922:Ciguatoxins