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羟甲芬太尼（Ｉ）是一个新的高强度高选择性阿片μ受体激动剂。本文用ｃｉｓ－Ａ－Ｎ－［１－（２－羟基－２－苯乙基）－３－甲基－４－哌啶基］－苯胺（ＩＩ）或ｃｉｓ－Ｎ－［１－（苯甲酰甲基）－３－甲基－４－哌啶基］－苯胺（ＩＩＩ）作为前体合成了［１１Ｃ］－羟甲芬太尼，以便用正电子发射断层扫描（ＰＥＴ）来观察μ受体。通过水解ｃｉｓ－Ａ－羟甲芬太尼（Ｉ）和ｃｉｓ－Ｎ－［１－（苯甲酰甲基）－３－甲基－４－哌啶］－Ｎ－苯基丙酰胺（ｃｉｓ－ＩＶ）的４－Ｎ－丙酰基分别获得ＩＩ和ＩＩＩ。溴乙烷的格氏试剂与回旋加速器产生的［１１Ｃ］－二氧化碳反应后继而直接加入邻苯二甲酸二酰氯和２，６－二叔丁基吡啶生成同位素标记中间体［１１Ｃ］－丙酰氯。［１１Ｃ］－丙酰氯与ＯＨ－前体（ＩＩ）反应后再经ＨＰＬＣ分离纯化直接得［１１Ｃ］－羟甲芬太尼；［１１Ｃ］－丙酰氯与酮－前体（ＩＩＩ）反应后，再用硼氢化钠甲醇溶液处理，然后进行ＨＰＬＣ分离纯化得［１１Ｃ］－羟甲芬太尼。两种方法均可获得ｌｌ．１～１４．８ＧＢｑ／μｍｏｌ的特异性放射化学纯［１１Ｃ］－羟甲芬太尼。总共耗时为４０～５０ｍｉｎ（ＥＯＢ）。
Hydroxymeta fentanyl (I) is a new high-strength, highly selective opioid μ receptor agonist. In this paper, cis-A-N- [1- (2-hydroxy-2-phenylethyl) -3-methyl-4-piperidinyl] -aniline (II) Acylmethyl) -3-methyl-4-piperidinyl] -aniline (III) was synthesized as a precursor in order to observe μ by positron emission tomography (PET) body. By hydrolysis of cis-A-hydroxymethafentanil and cis-N- [1- (phenacyl) -3-methyl- IV) 4-N-propionyl groups to give II and III, respectively. The Grignard reagent of bromoethane reacts with [11C] -carbon dioxide produced by the cyclotron followed by the direct addition of phthaloyl dichloride and 2,6-di-tert-butylpyridine to the isotopically labeled intermediate [11C] -propionyl chloride. The reaction of [11C] -propionyl chloride with OH-precursor (II) and subsequent purification by HPLC gave [11C] -hydroxymetafentanil. After reaction of [11C] Then treated with sodium borohydride methanol solution, and then purified by HPLC [11C] -hydroxymeta fentanyl. Two methods are available ll. 1 ~ 14.8GBq / μmol of specific radiochemically pure [11C] -hydroxyfenfentanil. The total time is 40 ~ 50min (EOB).