Sulfur Derivatives of the Natural Polyarsenical Arsenicin A: Biologically Active,
Organometallic Arsenic–Sulfur Cages Related to the Minerals
Realgar and Uzonite
(±)-Arsenicin A (AsA), (±)-<b>1</b>, the first
natural polyarsenical to be isolated, has the adamantane-type structure
of the mineral arsenolite (As<sub>4</sub>O<sub>6</sub>), in which
three of the oxygen atoms have been replaced by methylene groups to
give an organometallic, arsenic–oxygen cage of <i>C</i><sub>2</sub> symmetry. Heating of a benzene solution of AsA with
aqueous sodium sulfide produces, by reductive desulfurization of the
intermediate sulfur analog (±)-<b>2</b>, the monosulfide
cage (±)-<b>4</b>, which contains two As–As bonds
and which has a <i>C</i><sub>2</sub>-chiral cage structure
related to the mineral realgar (α-As<sub>4</sub>S<sub>4</sub>). At room temperature the reaction affords a chiral disulfide derivative
that exists as a pair of separable diastereomers, (±)-<b>3a</b> and (±)-<b>3b</b>, each of which contains a single As–As
bond and is structurally related to the mineral uzonite (As<sub>4</sub>S<sub>5</sub>). The crystal structures of the monosulfide (±)-<b>4</b> and the diastereomeric disulfides (±)-<b>3a</b> and (±)-<b>3b</b> have been determined. As for AsA, the
sulfur derivatives exhibit strong UV absorptions and can be resolved
on a Chiralpak IA column. The monosulfur cage (±)-<b>4</b> is considerably more potent and more selective than AsA and the
current “arsenical gold standard”, arsenic(III) oxide
as Trisenox, against the acute promelocytic leukemia cells (NB4) and
certain solid cancer cell lines
