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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
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, práce podpořená grantem
Grantová podpora
NS10365
MZ0
CEP - Centrální evidence projektů
- MeSH
- chromatografie na tenké vrstvě MeSH
- deuterium chemie MeSH
- glutamáty chemie MeSH
- hydroxyprogesterony chemie MeSH
- izotopové značení metody MeSH
- magnetická rezonanční spektroskopie MeSH
- molekulární struktura MeSH
- oxidace-redukce MeSH
- pregnanolon analogy a deriváty chemická syntéza chemie MeSH
- receptory N-methyl-D-aspartátu antagonisté a inhibitory MeSH
- rozpouštědla chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem 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.
Citace poskytuje Crossref.org
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- $a Synthesis of deuterium labeled NMDA receptor inhibitor - 20-Oxo-5β-[9,12,12-(2)H(3)]pregnan-3α-yl-L-glutamyl 1-ester / $c Vojtech Kapras, Alena Slavickova, Eva Stastna, Ladislav Vyklicky Jr., Karel Vales, Hana Chodounska
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