Synthesis of Deuterium-Labeled Androst-5-ene-17β, 19-diol and Its 4-Ene Isomer as Internal Standards for the Determination of the 19-Oxygenation of Aromatase Inhibitors Using GC-MS
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概要
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[3β, 7,7,17α-^2H_4]Androst-5-ene-17β, 19-diol (6) and [3,3,7,7,-^2H_4]androst-4-ene-17β, 19-diol (15-d_4) were synthesized as internal standards for gas chromatographic-mass spectrometric analysis of the 19-hydroxylation of androst-5-en-17-one (1) and its 4-ene isomer 2,inhibitors of estrogen biosynthesis, using human placental aromatase. Treatment of [7,7-^2H_2]3β-tosylate 3 with Zn-NaI-D_2O, followed by reduction with NaBD_4,gave compound 6 (d_4,79.8 atom%). Compound 15-d_4 was synthesized via 3β, 17β-dihydroxy-5-en-7-one 10 as a key intermediate. Deoxygenation of the 5-en-7-one 10 and [7,7-^2H_2]17β-hydroxy-4-en-3-one 13-d_2,produced from compound 10 in two steps, with AlCl_2D_2 was used for the deuterium labeling reaction, producing compound 15-d_4 (d_4,93.5 atom%). The 19-oxygenation products of aromatase inhibitors 1 and 2 could be analyzed, after NaBH_4 reduction, as the corresponding 17β, 19-diol bis-trimethylsilyl ethers using the internal standards 6 and 15-d_4.
- 公益社団法人日本薬学会の論文
- 1999-02-15
著者
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NUMAZAWA Mitsuteru
Tohoku College of Pharmacy
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Nagaoka Masao
Tohoku College Of Pharmacy
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MORIO Makoto
Tohoku College of Pharmacy
関連論文
- Synthesis and GC-MS of 6-Alkylestradiols, Possible Aromatase Reaction Products of 6-Alkylandrostenediones
- Kinetic Analysis of Reversible Inhibition of 16α-Hydroxyandrostenedione Aromatization in Human Placental Microsomes by Suicide Substrates of Androstenedione Aromatization
- Gas Chromatography-Mass Spectrometric Determination of Activity of Human Placental Aromatase Using 16α-Hydroxyandrostenedione as a Substrate
- Synthesis of 19-Oxygenated 4β, 5β-Epoxy Derivatives of 16α-Hydroxyandrostenedione as Mechanistic and Catalytic Probes for Aromatase Reaction
- C(10)-C(19) Bond Cleavage Reaction of 19-Oxygenated Androst-4-ene-3,6-dione Steroids under Various Conditions
- Improved Synthesis and Molecular Modeling of 4β,19-Dihydroxyandrost-5-en-17-one, an Excellent Inhibitor of Aromatase
- Aromatization of 19-Oxygenated Androst-4-ene-3,6,17-triones with Human Placental Microsomes
- Synthesis and Biochemical Studies of 19-Oxygenated Derivatives of 6α- and 6β-Methylandrostenediones as Catalytic Probes for the Active Site of Aromatase
- 19-Oxygenation of C_-Steroids with an A, B-Ring Enone Structure, Competitive Inhibitors of Estrogen Biosynthesis, with Human Placental Aromatase
- Aromatase Inhibition by 4β, 5β-Epoxides of 16α-Hydroxyandrostenedione and Its 19-Oxygenated Analogs, Potential Precursors of Estriol Production in the Feto-Placental Unit
- Identification of 16α, 19-Dihydroxyandrostenedione in the Serum of Pregnant Women by Gas Chromatography-Mass Spectrometry
- Synthesis of Deuterium-Labeled Androst-5-ene-17β, 19-diol and Its 4-Ene Isomer as Internal Standards for the Determination of the 19-Oxygenation of Aromatase Inhibitors Using GC-MS
- Stereochemistry of NaBH_4 Reduction of a 19-Carbonyl Group of 3-Deoxy Androgens. Synthesis of [19S-^3H]- and [19R-^3H]-Labeled Aromatase Inhibitors Having a 19-Hydroxy Group
- DETERMINATION OF AROMATASE ACTIVITY INVOLVED IN THE FORMATION OF ESTRIOL WITH HUMAN PLACENTAL MICROSOMES AND ITS KINETIC PROPERTIES
- Formation of 17β-Alkoxy-16-keto Steroids by Reaction of 16α-Hydroxy-17-keto and 17β-Hydroxy-16-keto Steroids with Trimethylsilyl Iodide in the Presence of Alkyl Alcohols
- Structure-Activity Relationships of Estrogen Derivatives as Aromatase Inhibitors. Effects of Heterocyclic Substituents
- Mechanistic Studies of Deoxygenation of Steroidal Ring-D 16,17-Ketols with trimethylsilyl Iodide
- Deoxygenation of Steroidal Ring-D 16,17-Ketols with Trimethylsilyl Iodide
- Aromatase Inactivation by a Suicide Substrate, Androst-5-ene-4,7,17-trione : The 5β, 6β-Epoxy-19-oxo Derivative, as a Possible Reactive Electrophile Irreversibly Binding to the Active Site
- 19-Oxygenated Derivatives of Androst-4-ene-6,17-dione and Androst-5-ene-4,17-dione as Catalytic Probes for the Active Site of Aromatase
- Gas Chromatography-Mass Spectrometric Study of 19-Oxygenation of the Aromatase Inhibitor 19-Methylandrostenedione with Human Placental Microsomes(Analytical Biochemistry)
- Reduction of 1,4-Dien-3-one Steroids with LiAl^2H_4 or NaB^2H_4 : Stereospecific Deuterium-Labeling at the C-1α Position of a 4-En-3-one Steroid
- Studies of the Time-Dependent Inactivation of Aromatase by 4β, 5β-Epoxy-6-one and 5β, 6β-Epoxy-4-one Steroids under Various Conditions
- Synthesis and Biochemical Properties of 6-Bromoandrostenedione Derivatives with a 2,2-Dimethyl or 2-Methyl Group as Aromatase Inhibitors(Medicinal Chemistry)