1278. Deuterium and tritium exchange reactions of phenols and the synthesis of labelled 3,4-dihydroxyphenylalanines
1278. Deuterium and tritium exchange reactions of phenols and the synthesis of labelled 3,4-dihydroxyphenylalanines
复制标题
1278. 酚的氘和氚交换反应以及标记的3,4-二羟基苯丙氨酸的合成
DOI：
10.1039/jr9650006914
复制
发表时间：
1965
期刊：
影响因子：
--
通讯作者：
L. Ogunkoya
中科院分区：
文献类型：
--
作者：
G. W. Kirby;L. Ogunkoya
概述了通过在碱性溶液中交换用氘和氚标记酚的制备程序。讨论了在邻位和对位用氚标记的酚在生物合成研究中的使用。所开发的方法通过合成在每个核和侧链位置进行特异性标记的 (&)-3, 4-二羟基苯丙氨酸来说明。 Ingold、Raisin 和 Wilson 在他们的早期研究中表明，当在碱性氧化氘中加热时，酚类会将芳基氢交换为氘。例如，在苯酚本身中，三个芳基氢在这些条件下进行交换。这些和后来的两项研究证实，交换主要发生在酚羟基的邻位和对位位置。在更强制的条件下，例如液氨中的钾酰胺，也观察到了元交换。必须牢记即使在水系统中也可能发生某些元交换的可能性（见下文）。近年来，人们对复杂酚类化合物，特别是酚类生物碱的生物合成表现出了很大的兴趣。^ 对于这项工作，有必要合成放射性标记的酚来测试作为天然物质的生物前体。似乎在碱性氚水中交换酚类前体将提供一种方便且廉价的标记程序。考虑到这一点，本次研究的目的是建立可用于制备规模的通用氚化方法。这些实验室的最新经验表明 6 $7 一元酚和儿茶酚不会在生物系统中交换正氚和对氚，并且以这种方式标记的酚确实可以成功地用于生物合成研究。然而，已知间苯二酚和间苯三酚衍生物会极其迅速地发生核变化。这将严重限制相应标记材料在生物合成工作中的使用。首先将描述各种简单酚的氘化和氚化，特别关注交换反应的特异性。然后将通过合成在每个不同的核和侧链位置上进行特异性标记的(&)-3, 4-二羟基苯丙氨酸来说明一般方法。
Preparative procedures are outlined for the labelling of phenols with deuterium and tritium by exchange in alkaline solution. The use of phenols, labelled with tritium at the ortho and para positions, in biosynthetic investigations is discussed. The methods developed are illustrated by the synthesis of (&)-3, 4-dihydroxyphenylalanine labelled specifically at each of the nuclear and side-chain positions.IN their early investigations Ingold, Raisin, and Wilson showed that phenols, when heated in alkaline deuterium oxide, exchanged aryl hydrogens for deuterium. For example, in phenol itself three aryl hydrogens were exchanged under these conditions. These and later 2 studies established that exchange occurred predominantly at positions ortho and para to phenolic hydroxyl groups. Under more forcing conditions, for example with potassamide in liquid ammonia, meta exchange has also been ob~ erved.~ The possibility that some meta exchange might take place even in aqueous systems must be kept in mind (see below). In recent years much interest has been shown in the biosynthesis of complex phenolic compounds, especially the phenolic alkaloid^.^ For this work it was necessary to synthesise radio-labelled phenols to test as biological precursors of the natural substances. It seemed that the exchange of phenolic precursors in alkaline tritiated water would provide a convenient and inexpensive labelling procedure. With this in mind, the present investigation was undertaken to establish general tritiation methods which could be applied on a preparative scale. Recent experience in these laboratories has shown 6 $7 that monohydric phenols and catechols do not exchange ortho and para tritium in biological systems, and that phenols labelled in this way may indeed be used successfully in biosynthetic studies. Resorcinol and phloroglucinol derivatives are, however, known to undergo nuclear ex: change extremely rapidly. This would seriously limit the use of the correspondingly labelled materials in biosynthetic work. The deuteration and tritiation of a variety of simple phenols will first be described, special attention being paid to the specificity of the exchange reaction. The general methods will then be illustrated by the synthesis of (&)-3, 4-dihydroxyphenylalanine labelled specifically in each of the different nuclear and sidechain positions.