Synthesis and P-388 Antitumor Properties of the Four Diastereomeric l-Hydroxy-3,4-diaminocyclohexane-Cl₂Pt^II Complexes

Synthesis and antileukemic activity in vivo of the four diastereomeric l-hydroxy-3₅4-diaminocyclohexane-Cl₂Pt^II complexes (Cl₂Pt^II-3a-d) are described. Respective bis(phenylmethyl) (lα,2α,4β)-, (lα,2α,4α)-, (lα,2β,4β)-, and (lα, 2β 4α)- (4-hydroxy- 1,2-cyclohexanediyl) bis (carbamates) (5a, 5b, 7a, 7b) were prepared by hydroboration-oxidation of the bis(carbobenzoxyamino) derivatives (4, 5) of cis- and trans-4,5-diaminocyclohexene. The relative stereochemistry of intermediates 5a and 5b was established by correlation with the alcohol obtained by NaBH₄reduction of bis(phenylmethyl) (lα,2α,3α,4α)-(3,4-epoxy-l,2-cyclohexanediyl)bis(carbamate) (8), the all-cis stereochemistry of which was unambiguously determined by X-ray crystallographic analysis. In the P-388 murine leukemia model these monohydroxycyclohexanediamine-Pt¹¹ complexes were more effective than the Pt¹¹ complexes of the related diol diamines la-e but were less active than the cisplatin positive control.