Synthesis of deuterium labeled NMDA receptor inhibitor - 20-Oxo-5β-[9,12,12-(2)H(3)]pregnan-3α-yl-L-glutamyl 1-ester.

Autor: Kapras V; Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i., Flemingovo nam. 2, Prague 6 - Dejvice, Czech Republic., Slavickova A, Stastna E, Vyklicky L Jr, Vales K, Chodounska H
Jazyk: angličtina
Zdroj: Steroids [Steroids] 2012 Feb; Vol. 77 (3), pp. 282-7. Date of Electronic Publication: 2011 Dec 19.
DOI: 10.1016/j.steroids.2011.12.019
Abstrakt: 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.
(Copyright © 2011 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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