Synthesis of deuterium-labeled 17-hydroxyprogesterone suitable as an internal standard for isotope dilution mass spectrometry

Journal Article · Tue Mar 01 04:00:00 EST 1988 · Steroids; (United States)

DOI:https://doi.org/10.1016/0039-128X(88)90019-0· OSTI ID:6464774

Shimizu, K; Yamaga, N; Kohara, H

A synthesis is reported of 17-hydroxyprogesterone, labeled with four atoms of deuterium at ring C and suitable for use as an internal standard for isotope dilution mass spectrometry. Base-catalyzed equilibration of methyl 3 alpha-acetoxy-12-oxo-cholanate (III) with /sup 2/H/sub 2/O, followed by reduction of the 12-oxo group by the modified Wolff-Kisher method using (/sup 2/H)diethylene glycol and (/sup 2/H)hydrazine hydrate afforded (11,11,12,12,23,23(-2)H)lithocholic acid (V). The Meystre-Miescher degradation of the side chain of V yielded 3 alpha-hydroxy-5 beta-(11,11,12,12(-2)H)pregnan-20-one (X). Oxidation of the 3,20-enol-diacetate of X with perbenzoic acid followed by saponification afforded 3 alpha,17-dihydroxy-5 beta-(11,11,12,12(-2)H)pregnan-20-one (XI). Oxidation of XI with N-bromoacetamide yielded 17-hydroxy-5 beta-(11,11,12,12(-2)H)pregnane-3,20-dione (XII). Bromination of XII followed by dehydrobromination yielded 17-hydroxy-(11,11,12,12(-2)H) progesterone (XIV), consisting of 0.3% /sup 2/H0-, 1.1% /sup 2/H/sub 1/-, 8.6% /sup 2/H/sub 2/-, 37.1% /sup 2/H/sub 3/-, 52.1% /sup 2/H/sub 4/-, and 0.8% /sup 2/H/sub 5/-species.

• Research Organization: Tottori Univ., School of Medicine, Yonago (Japan)
• OSTI ID: 6464774
• Journal Information: Steroids; (United States), Journal Name: Steroids; (United States) Vol. 51:3-4; ISSN STEDA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
CALIBRATION STANDARDS
CHEMICAL PREPARATION
DEUTERIUM
DRUGS
HORMONES
HYDROGEN ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPE DILUTION
ISOTOPES
KETONES
LABELLED COMPOUNDS
LIGHT NUCLEI
MASS SPECTROSCOPY
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
PREGNANES
PROGESTERONE
RADIOPHARMACEUTICALS
SPECTROSCOPY
STABLE ISOTOPES
STANDARDS
STEROID HORMONES
STEROIDS
SYNTHESIS
TRACER TECHNIQUES