Synthesis and P-388 Antitumor Properties of the Four Diastereomeric l-Hydroxy-3,4-diaminocyclohexane-Cl2PtII Complexes

Donald T. Witiak, David Rotella, Yong Wei, Joyce A. Filppi, Judith C. Gallucci

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Abstract

Synthesis and antileukemic activity in vivo of the four diastereomeric l-hydroxy-354-diaminocyclohexane-Cl2PtII complexes (Cl2PtII-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.

Original languageEnglish
Pages (from-to)214-217
Number of pages4
JournalJournal of Medicinal Chemistry
Volume32
Issue number1
DOIs
StatePublished - 1 Jan 1989

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Carbamates
Diamines
Cisplatin
Leukemia
Alcohols
X-Rays

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Witiak, Donald T. ; Rotella, David ; Wei, Yong ; Filppi, Joyce A. ; Gallucci, Judith C. / Synthesis and P-388 Antitumor Properties of the Four Diastereomeric l-Hydroxy-3,4-diaminocyclohexane-Cl2PtII Complexes. In: Journal of Medicinal Chemistry. 1989 ; Vol. 32, No. 1. pp. 214-217.
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abstract = "Synthesis and antileukemic activity in vivo of the four diastereomeric l-hydroxy-354-diaminocyclohexane-Cl2PtII complexes (Cl2PtII-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.",
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Synthesis and P-388 Antitumor Properties of the Four Diastereomeric l-Hydroxy-3,4-diaminocyclohexane-Cl2PtII Complexes. / Witiak, Donald T.; Rotella, David; Wei, Yong; Filppi, Joyce A.; Gallucci, Judith C.

In: Journal of Medicinal Chemistry, Vol. 32, No. 1, 01.01.1989, p. 214-217.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Synthesis and P-388 Antitumor Properties of the Four Diastereomeric l-Hydroxy-3,4-diaminocyclohexane-Cl2PtII Complexes

AU - Witiak, Donald T.

AU - Rotella, David

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AU - Gallucci, Judith C.

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N2 - Synthesis and antileukemic activity in vivo of the four diastereomeric l-hydroxy-354-diaminocyclohexane-Cl2PtII complexes (Cl2PtII-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.

AB - Synthesis and antileukemic activity in vivo of the four diastereomeric l-hydroxy-354-diaminocyclohexane-Cl2PtII complexes (Cl2PtII-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.

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