A concise method for the preparation of deuterium-labeled cortisone: Synthesis of [6,7-2H]cortisone

Agnieszka Sulima; Thomas E. Prisinzano; Thomas Spande; Jeffrey R. Deschamps; Noel Whittaker; Zeev Hochberg; Arthur E. Jacobson; Kenner C. Rice

doi:10.1016/j.steroids.2005.04.006

A concise method for the preparation of deuterium-labeled cortisone: Synthesis of [6,7-²H]cortisone

Agnieszka Sulima, Thomas E. Prisinzano, Thomas Spande, Jeffrey R. Deschamps, Noel Whittaker, Zeev Hochberg, Arthur E. Jacobson, Kenner C. Rice

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

A method is described for the synthesis of isotopically labeled cortisone from commercially available cortisone acetate through a Δ^4,6- dieneone. Direct deuteration of the dienone acetate with various catalysts in different solvent systems failed to give an isolable product. Initial hydrolysis of the side-chain ester of the Δ^4,6-dieneone and subsequent derivatization gave the key intermediate, 17α,20;20,21-bismethylenedioxy- pregna-4,6-diene-3,11-dione, which could be satisfactorily deuterated to the desired product. The availability of [6,7-²H]cortisone will provide a tool for the future study of the metabolism of cortisone in human tissues.

Original language	English
Pages (from-to)	763-769
Number of pages	7
Journal	Steroids
Volume	70
Issue number	11
DOIs	https://doi.org/10.1016/j.steroids.2005.04.006
State	Published - Oct 2005

Bibliographical note

Funding Information:
The authors (at LMC, NIDDK, DHHS) thank the National Institute on Drug Abuse, NIH, DHHS, for partial financial support of our research program, and thank Sonja Hess and Victor Livengood (NIDDK, NIH, DHHS) for mass spectral data and Drs. Martin Garaffo (NIDDK, NIH, DHHS) and Henry Fales (NHLI, NIH, DHHS) for discussions about mass spectrometric analyses of deuterated compounds. The X-ray crystallographic work was supported in part by the National Institute on Drug Abuse, NIH, DHHS, and the Office of Naval Research.

Funding

The authors (at LMC, NIDDK, DHHS) thank the National Institute on Drug Abuse, NIH, DHHS, for partial financial support of our research program, and thank Sonja Hess and Victor Livengood (NIDDK, NIH, DHHS) for mass spectral data and Drs. Martin Garaffo (NIDDK, NIH, DHHS) and Henry Fales (NHLI, NIH, DHHS) for discussions about mass spectrometric analyses of deuterated compounds. The X-ray crystallographic work was supported in part by the National Institute on Drug Abuse, NIH, DHHS, and the Office of Naval Research.

Funders	Funder number
Henry Fales
Sonja Hess and Victor Livengood
National Institutes of Health (NIH)
Office of Naval Research Naval Academy
National Institute on Drug Abuse
National Institute of Diabetes and Digestive and Kidney Diseases	Z01DK059501
National Institute of Diabetes and Digestive and Kidney Diseases
Department of Health and Human Services, State Government of Victoria
National Heart and Lung Institute

Keywords

11β-HSD
Cortisol
Cortisone
Deuterium-label
[6,7-H] Cortisone

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Endocrinology
Pharmacology
Clinical Biochemistry
Organic Chemistry

Access to Document

10.1016/j.steroids.2005.04.006

Cite this

@article{2a0c41c018bb4ba7bb9dd538346bc657,

title = "A concise method for the preparation of deuterium-labeled cortisone: Synthesis of [6,7-2H]cortisone",

abstract = "A method is described for the synthesis of isotopically labeled cortisone from commercially available cortisone acetate through a Δ4,6- dieneone. Direct deuteration of the dienone acetate with various catalysts in different solvent systems failed to give an isolable product. Initial hydrolysis of the side-chain ester of the Δ4,6-dieneone and subsequent derivatization gave the key intermediate, 17α,20;20,21-bismethylenedioxy- pregna-4,6-diene-3,11-dione, which could be satisfactorily deuterated to the desired product. The availability of [6,7-2H]cortisone will provide a tool for the future study of the metabolism of cortisone in human tissues.",

keywords = "11β-HSD, Cortisol, Cortisone, Deuterium-label, [6,7-H] Cortisone",

author = "Agnieszka Sulima and Prisinzano, \{Thomas E.\} and Thomas Spande and Deschamps, \{Jeffrey R.\} and Noel Whittaker and Zeev Hochberg and Jacobson, \{Arthur E.\} and Rice, \{Kenner C.\}",

note = "Funding Information: The authors (at LMC, NIDDK, DHHS) thank the National Institute on Drug Abuse, NIH, DHHS, for partial financial support of our research program, and thank Sonja Hess and Victor Livengood (NIDDK, NIH, DHHS) for mass spectral data and Drs. Martin Garaffo (NIDDK, NIH, DHHS) and Henry Fales (NHLI, NIH, DHHS) for discussions about mass spectrometric analyses of deuterated compounds. The X-ray crystallographic work was supported in part by the National Institute on Drug Abuse, NIH, DHHS, and the Office of Naval Research. ",

year = "2005",

month = oct,

doi = "10.1016/j.steroids.2005.04.006",

language = "English",

volume = "70",

pages = "763--769",

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T1 - A concise method for the preparation of deuterium-labeled cortisone

T2 - Synthesis of [6,7-2H]cortisone

AU - Sulima, Agnieszka

AU - Prisinzano, Thomas E.

AU - Spande, Thomas

AU - Deschamps, Jeffrey R.

AU - Whittaker, Noel

AU - Hochberg, Zeev

AU - Jacobson, Arthur E.

AU - Rice, Kenner C.

N1 - Funding Information: The authors (at LMC, NIDDK, DHHS) thank the National Institute on Drug Abuse, NIH, DHHS, for partial financial support of our research program, and thank Sonja Hess and Victor Livengood (NIDDK, NIH, DHHS) for mass spectral data and Drs. Martin Garaffo (NIDDK, NIH, DHHS) and Henry Fales (NHLI, NIH, DHHS) for discussions about mass spectrometric analyses of deuterated compounds. The X-ray crystallographic work was supported in part by the National Institute on Drug Abuse, NIH, DHHS, and the Office of Naval Research.

PY - 2005/10

Y1 - 2005/10

N2 - A method is described for the synthesis of isotopically labeled cortisone from commercially available cortisone acetate through a Δ4,6- dieneone. Direct deuteration of the dienone acetate with various catalysts in different solvent systems failed to give an isolable product. Initial hydrolysis of the side-chain ester of the Δ4,6-dieneone and subsequent derivatization gave the key intermediate, 17α,20;20,21-bismethylenedioxy- pregna-4,6-diene-3,11-dione, which could be satisfactorily deuterated to the desired product. The availability of [6,7-2H]cortisone will provide a tool for the future study of the metabolism of cortisone in human tissues.

AB - A method is described for the synthesis of isotopically labeled cortisone from commercially available cortisone acetate through a Δ4,6- dieneone. Direct deuteration of the dienone acetate with various catalysts in different solvent systems failed to give an isolable product. Initial hydrolysis of the side-chain ester of the Δ4,6-dieneone and subsequent derivatization gave the key intermediate, 17α,20;20,21-bismethylenedioxy- pregna-4,6-diene-3,11-dione, which could be satisfactorily deuterated to the desired product. The availability of [6,7-2H]cortisone will provide a tool for the future study of the metabolism of cortisone in human tissues.

KW - 11β-HSD

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KW - [6,7-H] Cortisone

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