Photorelease of carboxylic acids from 1-acyl-7-nitroindolines in aqueous solution: Rapid and efficient photorelease of L-glutamate
Photorelease of carboxylic acids from 1-acyl-7-nitroindolines in aqueous solution: Rapid and efficient photorelease of L-glutamate
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DOI：
10.1021/ja990931e
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发表时间：
1999-07-14
影响因子：
15
通讯作者：
Corrie, JET
中科院分区：
文献类型：
--
作者：
Papageorgiou, G;Ogden, DC;Corrie, JET
从可光裂解（笼式）前体中光释放生物活性化合物是研究生物过程的有用工具2，但神经活性氨基酸的快速、有效释放一直难以捉摸。我们和其他人3已经用各种不稳定性保护基团解决了这个问题。其中较好的试剂分别是 Givens4a 和 Hess, 4b 的对羟基苯甲酰甲基酯和 2, 2'-二硝基苯甲基酯。最近的一份报告5描述了 7-羟基香豆素-4-基甲基氨基甲酸酯的光释放，但这些速率受到氨基甲酸盐脱羧作用的限制（k≈ 150 s-1，pH 7，21 C）。 6 我们现在描述了稳定的 1-酰基-7-硝基二氢吲哚，它可以在中性水溶液中快速有效地光释放羧酸盐，包括 L-谷氨酸盐。相关试剂在二恶烷-CH2Cl2 中与~ 1% 水进行清洁光解，生成羧酸和硝基吲哚啉。 7a 显示了水的光解作用，但没有给出反应机理。 7 我们发现反应在水溶液中发生不同的过程。在化合物 8-10 中，5 位取代基确保了 C-7 处的硝化。之前的工作7使用5-溴化合物，但重原子可能会降低光解效率。我们使用了 CH2CO2Me 基团，预计也能增强水溶性。二氢吲哚 3 通过 1, 5-二乙酰二氢吲哚 1 的 Tl (NO3) 3 氧化 8 和 2 的酸性甲醇解制备（方案 1）。根据需要对引入的酰基进行酰化和进一步转化(4 f 6)，然后进行硝化9，同时除去叔丁基保护基团(在6和7中)，得到8-10。该路线避免了 7-硝基二氢吲哚、7b 的困难酰化，尤其是谷氨酸中敏感侧链的酰化。 5-溴化合物11是通过相关路线由1-乙酰基-5-溴二氢吲哚制备的。 8 和 11 在中性水溶液（不排除 O2）中的光解表明 11 的转化效率降低约 2.5 倍
Photorelease of biologically active compounds from photocleavable (caged) precursors is a useful tool to study biological processes2 but rapid, efficient release of neuroactive amino acids has been elusive. We and others3 have approached the problem with various photolabile protecting groups. Among the better reagents are p-hydroxyphenacyl and 2, 2′-dinitrobenzhydryl esters of Givens4a and Hess, 4b respectively. A recent report5 describes photorelease from 7-hydroxycoumarin-4-ylmethyl carbamates, but these are rate-limited by decarboxylation of the carbamate salt (k≈ 150 s-1, pH 7, 21 C). 6 We now describe stable 1-acyl-7-nitroindolines that rapidly and efficiently photorelease carboxylates, including L-glutamate, in neutral aqueous solution. Related reagents undergo clean photolysis in dioxane-CH2Cl2 with∼ 1% water to yield a carboxylic acid and nitroindoline. 7a Photosolvolysis by the water was shown, but no reaction mechanism was given. 7 We found the reaction takes a different course in aqueous solution.In compounds 8-10 a 5-substituent ensured nitration at C-7. Previous work7 used 5-bromo compounds, but a heavy atom might lower the photolysis efficiency. We used a CH2CO2Me group that was also expected to enhance aqueous solubility. Indoline 3 was prepared by Tl (NO3) 3 oxidation8 of 1, 5-diacetylindoline 1 and acidic methanolysis of 2 (Scheme 1). Acylation and further transformation of the introduced acyl group as required (4 f 6) followed by nitration9 concurrently removed tert-butyl protecting groups (in 6 and 7) to give 8-10. The route avoids a difficult acylation of 7-nitroindolines, 7b especially with sensitive side chains as in glutamic acid. 5-Bromo compound 11 was prepared by a related route from 1-acetyl-5-bromoindoline. Photolysis of 8 and 11 in neutral aqueous solution (without excluding O2) showed 11 was converted∼ 2.5-fold less efficiently