title: Synthesis and P-388 antitumor properties of the four diastereomeric 1-hydroxy-3,4-diaminocyclohexane-Cl2PtII complexes.
abstract: Synthesis and antileukemic activity in vivo of the four diastereomeric 1-hydroxy-3,4-diaminocyclohexane-Cl2PtII complexes (Cl2PtII-3a-d) are described. Respective bis(phenylmethyl) (1 alpha,2 alpha,4 beta)-, (1 alpha,2 alpha,4 alpha)-, (1 alpha,2 beta,4 beta)-, and (1 alpha,2 beta,4 alpha)-(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 NaBH4 reduction of bis(phenylmethyl) (1 alpha,2 alpha,3 alpha,4 alpha)-(3,4-epoxy-1,2-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-PtII complexes were more effective than the PtII complexes of the related diol diamines 1a-e but were less active than the cisplatin positive control.
authors.affiliation: Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Ohio State University, Columbus 43210.
authors.forename: D T
authors.initials: DT
authors.lastname: Witiak
authors.forename: D P
authors.initials: DP
authors.lastname: Rotella
authors.forename: Y
authors.initials: Y
authors.lastname: Wei
authors.forename: J A
authors.initials: JA
authors.lastname: Filppi
authors.forename: J C
authors.initials: JC
authors.lastname: Gallucci
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D055598:Chemical Phenomena; D002621:Chemistry; D007941:Leukemia P388 / Q000188:drug therapy*; D007942:Leukemia, Experimental / Q000188:drug therapy*; D051379:Mice; D008958:Models, Molecular; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000627:therapeutic use; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C058119:dichloro-1-hydroxy-3,4-diaminocyclohexane platinum complex