Concise synthesis of arnottin I and (-)-arnottin II.
Application of the Buchwald protocol to the coupling of o-bromobenzoates and 1-tetralones directly affords benzodihydronaphthopyrones with a fused tetracyclic system. Aromatization of the 7,8-dimethoxy-2,3-methylenedioxy derivative yielded arnottin I, whereas oxidation with dioxirane afforded dihydroarnottin II composed of a spiro phthalide-tetralone system. Sharpless asymmetric dihydroxylation using AD-mix yielded optically active dihydroarnottin II with good enantioselectivity. The absolute stereochemistry of the stereogenic center in the (+)-spiro product was determined to be R by X-ray crystallographic analysis of the dibromo derivative. (+)-Dihydroarnottin II was subjected to successive bromination and dehydrobromination to prepare (-)-arnottin II. The R-configuration of natural (-)-arnottin II, previously assigned by application of the exciton chirality method to the Cotton effects observed in the CD spectrum, was confirmed by asymmetric synthesis.
Konno
Fujiko
F
Graduate School of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi, Inage, Chiba 263-8522, Japan.
Ishikawa
Tsutomu
T
Kawahata
Masatoshi
M
Yamaguchi
Kentaro
K
D001572:Benzofurans / Q000138:chemical synthesis* / Q000737:chemistry; D003374:Coumarins / Q000138:chemical synthesis* / Q000737:chemistry; D018360:Crystallography, X-Ray; D004149:Dioxoles / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D013237:Stereoisomerism
D001572:Benzofurans; D003374:Coumarins; D004149:Dioxoles; C517333:arnottin II; C414400:arnottin I