Synthesis and Structures of 9‑Oxabispidine Analogues of Cisplatin, Carboplatin, and Oxaliplatin

The literature synthesis of 9-oxabispidine
[OC6H10(NH)2, C] has
been revisited and optimized, which includes determination of the
crystal structures of C, the secondary component trans-(PhSO2)­NC4H6O­(CH2I)2 (trans-III), and the unexpected
solute intermediate OC6H10(NSO2Ph)2·1/2py (V·1/2py). The reaction of (1,5-hexadiene)­platinum
dichloride with C yields {OC6H10(NH)2}­PtCl2 (C1), which is converted
to {OC6H10(NH)2}­Pt­(cbdca)·5H2O (C2) and {OC6H10(NH)2}­Pt­(C2O4) (C3). In the
crystal, C1 forms a planar 2D network by N–H··Cl
and N–H··O hydrogen bonding. In the crystal structure
of C2, which is isomorphous to the parent bispidine compound
(A2), all complex molecules are encapsulated by a water
shell. While complexes C1 and C3 are virtually
insoluble in water, C2 dissolves quite well. The low
cytotoxicity of compounds C1–C3 is
explained by an increased polarity of the bonds in the C skeleton as a consequence of the electronegative O atom.