22 アニサチンの全合成(口頭発表の部)

抄録

Anisatin (1), isolated as a toxic component of Japanese Star Anise, is a sesquiterpene characterized by eight contifuous stereogenic centers, oxabicyclo[3.3.1] skeleton, and spiro β-lactone. Its challenging structure, as well as the stron bioactivity as a GABA antagonist, has attracted many synthetic organic chemists. Despite numerous synthetic studies reported to date, only one total synthesis has been achieved. Inspired by its challenging structure, we also initiated our own research program directed toward a total synthesis of thi sinteresting molecule. Our synthesis commenced with the synthesis of phenol 7 from the known mono-protected catechol in seven steps. Oxidation of 7 with iodobenzene diacetate yielded orthoquinone monoketal, which upon heating underwent intramolecular Diels-Alder reaction to privide tetracyclic compound 14. After a three-step conversion, the resulting ether 16 was treated with methyllithium in the presence of HMPA, which induced diastereoselective [2,3]-sigmatropic rearrangement. Thus, the quaternary carbon was constructed with complete stereoselectivity. Selective cleavage of the trisubstituted souble bond of 17 by careful ozonolysis, followed by treatment with potassium carbonate provided 19. After a six-step conversion, iodide 22 was subjected to halogen-lithium exchange, which caused intramolecular addition to ketone to provide bicylco[4.3.0] skeleton. The enol ether moiety of 23 was oxidized to α-hydroxylactone, and the allyl alcohol moiety was converted to epoxide to provide 27. Upon ammonolysis of the lactone moiety, intramolecular S_N2 reaction to epoxide took place to give, after acid treatment, the desired lactone 29. Removal of the primary hydroxy group and protection of the resultin g tertiary alcohol afforded 31. The vinyl group of 31 was converted to carboxylic acid, followed by deprotection of the primary hydroxy group. Crucial lactonization was performed with MNBA to yield desired β-lactone successfully. A three-step sequence involving dihydroxylation of the trisubstituted olefin afforded 1. Having achieved total synthesis of racemic anisatin, we turned our attention to asymmetric synthesis. Phenol 35 and epoxyalcohol 36 were condensed by Mitsunobu reaction. Resulting ether 37 was subjected to halogen-lithium exchange. Bis(diethylaluminium)sulfate facilitated intramolecular S_N2 reaction to afford 38. HPLC analysis revealed that 38 was enantiomerically pure. Further synthetic studies toward asymmetric synthesis are currently under way.