PHOTOCHEMISTRY OF ARYL HALIDES AND ITS APPLICATIONS

在初步调查中，我们发现(I)间氟苯酚和 4-氟色氨酸的衍生物经历了一种新的亲光性 含氟基团的置换反应，(Ii) 4-氯色氨酸和4-氯吲哚经历了同样有趣的 完全不同的光化学解离作用来产生吲哚自由基， 和(Iii)间氯苯酚根据极性的不同经历任一过程 溶剂的含量。此前有报道称，邻氯苯酚 经历了Photo-Wolff重排，即环收缩形成 乙烯酮中间体。我们建议对……进行系统的调查 卤代苯酚、4-卤代吲哚、卤代酪氨酸和 4-卤素甲藻，以实现与 关于反应中间体在这些反应中的依赖性 关于芳基卤化物的结构和实验条件。自.以来 卤代酪氨酸和4-卤代色氨酸可以结合到蛋白质和 固相合成多肽和/或多肽的常规方法 通过分子生物学的方法，虽然现有的光亲和标记 不能，而且所有的蛋白质都含有芳香氨基酸，光化学 卤代酪氨酸和卤色胺可能被开发成新的强大的 蛋白质化学中的光亲和标记方法。因此，我们也 建议探索将这些化合物用作光亲和标记在 与芝加哥大学和 在其他地方，建议的系统包括胰凝乳酶、芳基硫酸酯酶、色氨酸 抑制物，维甲酸结合蛋白和胰岛素：受体相互作用。 随着我们工作的进展，可能会开发更多的系统。 此外，由于蛋白质与其底物之间的共价结合 或受体可能导致其生物学上的深刻改变 功能，我们的研究可能会导致新药的设计和其他 生物活性物质。

In a preliminary investigation, we have found that (i) m-fluorophenol and derivatives of 4-fluorotryptophan undergo a novel photonucleophilic displacement reaction of the fluoro group, (ii) derivatives of 4-chlorotryptophan and 4-chloroindoles undergo an equally interesting but entirely different photochemical dissociation to generate indolyl radicals, and (iii) m-chlorophenol undergoes either process depending on the polarity of the solvent. It has been reported previously that o-chlorophenol undergoes a Photo-Wolff Rearrangement, i.e., a ring-contraction to form a ketene intermediate. We propose to carry out a systematic investigation on the photochemistry of halophenols, 4-haloindoles, halotyrosines and 4-halotrytophans in order to achieve a mechanistic understanding with regard to the dependence of the reactive intermediate in these reactions on the structure of the aryl halide and experimental conditions. Since halotyrosines and 4-halotryptophans may be incorporated into proteins and peptides by conventional methods of solid-phase peptide synthesis and/or by methods of molecular biology, while existing photoaffinity labels cannot, and all proteins contain aromatic amino acids, photochemistry of halotyrosines and halotryptophans may be developed into new powerful methods of photoaffinity labelling in protein chemistry. Therefore, we also propose to explore the use of these compounds as photoaffinity labels in collaboration with scientists both at the University of Chicago and elsewhere, systems proposed include chymotrypsin, arylsulfatases, Trp repressor, retinoid binding proteins and insulin:receptor interaction. Additional systems may be developed as our work progresses. Furthermore, since covalent binding between proteins and their substrates or receptors may cause a profound modification of their biological functions, our study may lead to the design of new drugs and other biologically active agents.