Bispidin-9,9-diol Analogues of Cisplatin, Carboplatin, and Oxaliplatin: Synthesis, Structures, and Cytotoxicity

3,7-Diallyl-bispidin-9-one (6) (bispidin-9-one = 3,7-diazabicyclo[3.3.1]­nonan-9-one) is converted to N-unsubstituted spiro­[bispidin-9,2′-[1,3]­dioxolane] (12; 35%). The ketal crystallizes in the forms of anhydrous 12a and the dihydrate 12b. The molecules in anhydrous 12a are linked to each other, forming N1–H1···N2–H2···N1* hydrogen-bond chiral helices of alternating chirality. In the dihydrate 12b, the ketal molecules are connected to a central string of water molecules by O3–H···O1 and O4–H···N1 hydrogen bonds, but not to themselves. Reaction of 12 with (1,5-hexadiene)­PtCl2 affords almost quantitatively spiro­[bispidin-9,2′-[1,3]­dioxolane]­PtCl2 (13). Cleavage of the ketal to retrieve the ketone produces the geminal diol (bispidin-9,9-diol)­PtCl2 (14; 85%). Compound 14 reacts with Ag2cbdca (cbdca = 1,1-cyclobutanedicarboxylate) to give the dihydrate (bispidin-9,9-diol)­Pt­(cbdca)·2H2O (15b), which can be dehydrated to obtain anhydrous (bispidin-9,9-diol)­Pt­(cbdca) (15a). Similarly, anhydrous (bispidin-9,9-diol)­Pt­(oxalate) (16) is obtained. Crystal structures of 14 and 15b reveal association by various forms of O–H···O, O–H···Cl, N–H···Cl, and N–H···O hydrogen bonds. Biological studies showed a moderate cytotoxic activity of the bispidin-9,9-diol complexes 14–16, compared to the 9,9-unsubstituted bispidine complexes. No unspecific cytotoxicity of 14–16 up to 316 μM was found against the noncancer cell line HEK293.