Concise synthesis of arnottin I and (-)-arnottin II
Fujiko Konno1, Tsutomu Ishikawa, Masatoshi Kawahata
1Graduate School of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi, Inage, Chiba 263-8522, Japan.
Abstract:
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.
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