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The resolution and improved synthesis of the naturallyoccurring,adamantane-type, tetraarsenical (±)-Arsenicin A is reported.The five-step synthesis of (±)-Arsenicin A from methylenebis(phenylarsinicacid) affords (±)-Arsenicin A as air-stable, colorless crystalshaving an mp of 182–184 °C after column chromatographyand recrystallization from benzene (overall yield: 36%). The resolutionof (±)-Arsenicin A was achieved by preparative HPLC on a ChiralpakIA column with the use of dichloromethane as eluent to give both enantiomersin >99% enantiomeric purity (HPLC); the isolated enantiomers had[α]58920= −60.2and .3 (0.01% NEt3/CH2Cl2). (S)-(−)-Arsenicin A, having an mp of 241–242°C from dichloromethane, crystallizes in the space group P212121with one moleculehaving the (SAs,SAs,SAs,SAs) or overall Sconfiguration in the asymmetric unit.The adamantane-type structure of (±)-Arsenicin A is reminiscentof arsenic(III) oxide (As4O6), but where threeof the oxygen atoms in the inorganic oxide have been replaced by methylenegroups in a chiral C2arrangement. ((±)-ArsenicinA, mp 182–184 °C, crystallizes from benzene in the centrosymmetricalspace group P1̅: the unit cell of the crystalcontains two independent pairs of molecules, the molecules in eachpair being related by an inversion center.) The individual enantiomersof (±)-Arsenicin A racemize in the presence of traces of acid,and high-level ab initio calculations have been performed to examinethe mechanism of the process. (±)-Arsenicin A exhibits a 21-foldgreater inhibition of the induction of proliferation arrest and inducescell death at a 27-fold lower concentration in the acute promyelocyticleukemia cell line than the current “arsenical gold standard”,arsenic(III) oxide (Trisenox). (±)-Arsenicin A is also more potentthan arsenic(III) oxide for the induction of proliferation arrestin two other cancers with particularly bad prognoses: pancreatic adenocarcinomaand glioblastoma. [ABSTRACT FROM AUTHOR]