Synthesis of deuterium‐labeled d₃‐androstenone and d₃‐skatole for boar taint analysis

Abstract

The steroidal pig pheromone androstenone (5α-androst-16-en-3-one) as well as the indole derivate skatole are known to be the major compounds contributing to boar taint. The preparation of 2 H-labeled internal standards of androstenone and skatole for stable isotope dilution assay-gas chromatography-mass spectrometry analysis of pig back fat samples is presented. The synthesis of d 3 -androstenone is highlighted by a palladium catalyzed deuteration of a Δ5,6-double bond of a hydrophobic steroid in a polar, D 2 O-containing solvent mixture. Moreover, the utilization of D 2 O as a deuterium source with in situ formation of D 2 by means of Mg 0 was found to be a very feasible and convenient alternative with respect to costs and technical effort.

The Deuterated “Magic Methyl” Group: A Guide to Site‐Selective Trideuteromethyl Incorporation and Labeling by Using CD3Reagents

“…Following the pioneering work of Grigg and co‐workers, who first reported the BH strategy , Cai and his colleagues reported a simple and straightforward methylation approach in the synthesis of biologically important alkylated indoles and pyrroles with cyclopentadienyl iridium catalyst (Scheme 6a) [36] . [D 3 ]methylation of indole delivered [D 3 ]skatole, which is widely used to study metabolic kinetics, in 81 % yield [37] . Although noble metal catalysts such as Ir and Ru are well known to be effective for the BH alkylation, they have limitations due to the price, toxicity and difficulty of recovery.…”

“…[36] [D 3 ]methylation of indole delivered [D 3 ]skatole, which is widely used to study metabolic kinetics, in 81 % yield. [37] Although noble metal catalysts such as Ir and Ru are well known to be effective for the BH alkylation, they have limitations due to the price, toxicity and difficulty of recovery. To address this issue, Morrill entered the topic of indole alkylation and suggested an inexpensive and benign Knölker‐type (cyclopentadienone)iron carbonyl complex precatalyst [Fe1] (Scheme 3 ), activated with trimethylamine N‐oxide for the C‐methylation of a broad range of substrates, including indole.…”

Development of a Candidate Reference Method for the Simultaneous Quantitation of the Boar Taint Compounds Androstenone, 3α-Androstenol, 3β-Androstenol, Skatole, and Indole in Pig Fat by Means of Stable Isotope Dilution Analysis–Headspace Solid-Phase Microextraction–Gas Chromatography/Mass Spectrometry

“…All chemicals were obtained from Sigma-Aldrich (Steinheim, Germany), Roth (Karlsruhe, Germany), VWR (Darmstadt, Germany), or Alfa Aesar (Karlsruhe, Germany) in analytical grade and were used without further purification unless stated otherwise. The deuterium-labeled internal standards (Figure ) androstenone- d 3 ( 1 , ANON- d 3 ), 3β-androstenol- d 3 ( 2 , 3β-OL- d 3 ), and skatole- d 3 ( 3 , SK- d 3 ) were prepared and characterized in our laboratory as previously reported . In brief, ANON- d 3 was prepared from commercially available 3β-hydroxyandrost-5-en-17-one by selective deuteration of its B-ring double bond using Pd/C and a Mg 0 /D 2 O/dioxane system, followed by a Shapiro reaction of the ketone to provide 3β-OL- d 3 , which was finally oxidized using PDC to obtain ANON- d 3 in 32% overall yield.…”

Frontispiece: The Deuterated “Magic Methyl” Group: A Guide to Site‐Selective Trideuteromethyl Incorporation and Labeling by Using CD3 Reagents

“…[36] [D 3 ] methylation of indole delivered [D 3 ]skatole, which is widely used to study metabolic kinetics, in 81 % yield. [37] Although noble metal catalysts such as Ir and Ru are well known to be effective for the BH alkylation, they have limitations due to the price, toxicity and difficulty of recovery. To address this issue, Morrill entered the topic of indole alkylation and suggested an inexpensive and benign Knölker-type (cyclopentadienone)iron carbonyl complex precatalyst [Fe1] (Scheme 3), activated with trimethylamine N-oxide for the C-methylation of a broad range of substrates, including indole.…”