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Synthesis of deuterium labeled cholesterol and steroids and their use for metabolic studies
Author(s) -
Goad L. J.,
Breen M. A.,
Rendell N. B.,
Rose M. E.,
Duncan J. N.,
Wade A. P.
Publication year - 1982
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/bf02534596
Subject(s) - pregnenolone , steroid , chemistry , sterol , yield (engineering) , tritium , stereochemistry , cholesterol , biochemistry , hormone , materials science , physics , nuclear physics , metallurgy
A simple method is described for the preparation of [6,7,7 −2 H 3 ] sterols and steroids. The synthesis starts with a Δ 5 ‐sterol or steroid and involves preparation of the 6‐oxo‐3α,5α‐cyclosteroid, base exchange in the presence of deuterium oxide to introduce two deuteriums at the C‐7 position and sodium borodeuteride reduction of the 6‐oxo group to introduce the third deuterium atom at C‐6. Rearrangement of the [6,7,7 −2 H 3 ]6α‐hydroxy‐3α,5α‐cyclosteroid then gives the desired [6,7,7 ‐2 H 3 ]‐Δ 5 sterol or steroid. [6,7,7 −2 H 3 ]Cholesterol, [6,7,7 −2 H 3 ]pregnenolone and [6,7,7 −2 H 3 ]3β‐hydroxyandrost‐5‐en‐17‐one were synthesized in this fashion and [6,7,7 −2 H 3 ]progesterone was prepared from the [6,7,7 −2 H 3 ]pregnenolone. Three examples of the use of these deuchromatography‐mass spectrometry. The chrysophyte alga, Ochromonas malhamensis , was shown to be capable of introducing an extra methyl or ethyl group at C‐24 of the side chain of [6,7,7 −2 H 3 ]cholesterol to yield brassicasterol and poriferasterol, respectively. The ovary of the echinoderm, Asterias rubens , was demonstrated to metabolize [6,7,7 −2 H 3 ]progesterone to yield mainly the 5α‐isomers of pregnane‐3,20‐dione and 3β‐hydroxypregnan‐20‐one. However, the 5β‐isomers of these compounds were also detected as minor products for the first time as progesterone metabolites in this animal. Isolated oocytes of the frog, Xenopus laevis , produced a number of metabolites of [6,7,7 −2 H 3 ]progesterone. In this report, two of them were shown to be 17α‐hydroxy‐pregn‐4‐en‐3,20‐dione and 20α‐hydroxypregn‐4‐en‐3‐one.