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Synthesis of deuterium labeled NMDA receptor inhibitor - 20-Oxo-5β-[9,12,12-(2)H(3)]pregnan-3α-yl-L-glutamyl 1-ester
Vojtech Kapras, Alena Slavickova, Eva Stastna, Ladislav Vyklicky Jr., Karel Vales, Hana Chodounska
Language English Country United States
Document type Journal Article, Research Support, Non-U.S. Gov't
Grant support
NS10365
MZ0
CEP Register
- MeSH
- Chromatography, Thin Layer MeSH
- Deuterium chemistry MeSH
- Glutamates chemistry MeSH
- Hydroxyprogesterones chemistry MeSH
- Isotope Labeling methods MeSH
- Magnetic Resonance Spectroscopy MeSH
- Molecular Structure MeSH
- Oxidation-Reduction MeSH
- Pregnanolone analogs & derivatives chemical synthesis chemistry MeSH
- Receptors, N-Methyl-D-Aspartate antagonists & inhibitors MeSH
- Solvents chemistry MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
20-Oxo-5β-[9,12,12-(2)H(3)]pregnan-3α-yl-l-glutamyl 1-ester 11 was synthesized as an internal standard for quantification of a neuroprotective NMDA receptor ligand, 20-oxo-5β-pregnan-3α-yl-l-glutamyl 1-ester 18 and its metabolites, in plasma and tissue. 11α-Hydroxy-progesterone (1) was reduced under basic conditions to yield the corresponding 5β-steroid. Protection of the 3- and 20-oxo groups and oxidation of the 11α-hydroxy group was then followed by a deuterium exchange, conducted under basic conditions using deuterated methanol. Next, the carbonyl moiety at C-11 was reduced and the 11α-hydroxyl group removed through utilization of the Barton-McCombie reaction. Subsequent deprotection of the 3- and 20-acetals and stereoselective reduction of the 3-oxo group gave the desired trideuterated pregnanolone (8). This was coupled with protected glutamic acid, which was then deprotected to yield [9,12,12-(2)H(3)]-pregnanolone glutamate (11) with >99% isotopic purity.
References provided by Crossref.org
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