Synthesis of deuterium labeled NMDA receptor inhibitor - 20-Oxo-5¦Â-[9,12,12-²H₃]pregnan-3¦Á-yl-l-glutamyl 1-ester

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• 作者：Vojtech Kapras^a ; ^b ; Alena Slavickova^a ; Eva Stastna^a ; ^{stastna@uochb.cas.cz} ; Ladislav Vyklicky Jr.^c ; Karel Vales^c ; Hana Chodounska^a ; ^d
• 关键词：NMDA receptor ; Neuroprotection ; Deuterium labeling
• 刊名：Steroids
• 出版年：2012
• 出版时间：February 2012
• 年：2012
• 卷：77
• 期：3
• 页码：282-287
• 全文大小：258 K

文摘

20-Oxo-5¦Â-[9,12,12-²H₃]pregnan-3¦Á-yl-l-glutamyl 1-ester 11 was synthesized as an internal standard for quantification of a neuroprotective NMDA receptor ligand, 20-oxo-5¦Â-pregnan-3¦Á-yl-l-glutamyl 1-ester 18 and its metabolites, in plasma and tissue. 11¦Á-Hydroxy-progesterone (1) was reduced under basic conditions to yield the corresponding 5¦Â-steroid. Protection of the 3- and 20-oxo groups and oxidation of the 11¦Á-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 11¦Á-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 [9,12,12-²H₃]-pregnanolone glutamate (11) with >99 % isotopic purity.