RADICAL INDUCED DEAMINATION OF PRIMARY & SECONDARY AMINES BY TRIBUTYLTIN TRITIDE

一级、二级和三级脂肪族或脂环族 异氰酸酯、异硫氰酸酯和异硫氰酸酯 在自由基反应条件下选择性还原为 使用四叔丁基四氢呋喃作为还原剂的相应碳氢化合物。这些 自由基反应可以在中性条件下进行，而不需要 结构调整的可能性。他们的反应是 在概念上类似于初级和次级的脱氧 醇类化合物(巴顿反应)和伯基的选择性取代 氢原子的氨基功能是一种理想的反应 许多天然产品的标签。由于自由基致脱氨基 TBTH对异氰化物的反应是具有相当大价值的一般反应， 高度标记的技术性贸易壁垒的可获得性意味着该程序可以 被开发为一种氚标记技术。一种新的合成方法 异氰化物底物用于自由基氚反应需要 氨基的甲酰化反应使用乙酸甲酸酐或 对-硝基苯基甲酸酯与磷脱水 二氯甲烷中的氯氧基/三乙胺 前驱体的产率很高。对于羟基化化合物，甲酰化 氨基之后是乙酸酐的O-过乙酰化反应。 据报道，异硫氰酸酯首先被还原成异氰化物 在脱胺之前，与异氰化物相比几乎没有什么优势 路线。然而，异硫氰酸酯在较高的化学产率下形成。 而不是仲异氰酸酯和叔异氰化物，因此可能是 在有限的情况下有利。异氰酸酯与四叔丁基四氢呋喃的反应 需要偶氮二异丁腈(AIBN)作为引发剂， 和热量，相对容易还原的是三级&>二级&>； 主要的。芳香族异氰酸酯在这些反应下不会被还原 条件。标题：自由基诱导的初级和初级脱氨基 三丁基锡的仲胺(续)我们已应用 该技术用于合成2-脱氧葡萄糖和氨基葡萄糖 作为开始的材料。氨基葡萄糖从 盐酸盐转化为游离胺，然后N-甲酰化。这个 以N-甲酰氨基葡萄糖为原料，用醋酸酐进行过乙酰化反应。 产品脱水得到2-氨基葡萄糖异氰酸酯，该产品 分离纯化后用于标记反应。氰化物提取 在苯中与新制的三丁基四氢化锡在2位 在催化量的AIBN存在下，在80oC下反应2小时 生成四-O-乙酰基-[2-2H]-脱氧葡萄糖。~2H核磁共振波谱分析 光谱分析显示有两个重氢峰，分别位于1.5ppm和2ppm。 脱乙酰基得到所需的[2-2H]-脱氧葡萄糖。带着相同的 程序制备了四-O-苯甲酰-[2-2H]-脱氧葡萄糖，但没有 去苯甲酰化，以便于高效液相色谱分析。在一种不同的 应用，同样的方法也适用于色氨酸甲酯。 以生成相应的异氰化物。这种反应是一种模式 关于合成α-氚或氚的一般方法 从氨基酸中标记的羧酸。氚标记法 目前正在建设中，并将于近期完工。 未来。

Primary, secondary, and tertiary aliphatic or alicyclic isocyanides, isothiocyanates and isoselenocyanates are smoothly and selectively reduced under free radical reaction conditions to the corresponding hydrocarbons using TBTH as a reducing agent. These radical reactions can be performed under neutral conditions without the possibility of structural rearrangements. The reaction is conceptually similar to the deoxygenation of primary and secondary alcohols (Barton reaction), and the selective replacement of a primary amino function by a hydrogen atom is a desirable reaction for the labelling of many natural products. Since radical-induced deamination of isocyanides by TBTH is a general reaction of considerable value, the availability of highly labelled TBTT means that this procedure can be developed as a tritium labelling technique. Synthesis of isocyanide substrates for the radical tritiation reaction requires formylation of the amino function using acetic formic anhydride or p-nitrophenyl formate followed by dehydration with phosphorus oxychloride/triethylamine in methylene dichloride to provide the precursor in good yield. For hydroxylated compounds, formylation of the amino group is followed by O-peracetylation with acetic anhydride. It is reported that isothiocyanates are first reduced to isocyanides before deamination, and have little advantage over the isocyanide route. However, isothiocyanates are formed at higher chemical yields than secondary and tertiary isocyanides, and may therefore be advantageous in limited cases. Reaction of isocyanides with TBTH requires the presence of azobisisobutyronitrile (AIBN) as initiator, and heat, and the relative ease of reduction is tertiary > secondary > primary. Aromatic isocyanides are not reduced under these reaction conditions. TITLE: Radical-Induced Deamination of Primary and Secondary Amines by Tributyltin Tritide (Continued) We have applied this technique to the synthesis of 2-deoxyglucose and used glucosamine as the starting material. Glucosamine was liberated from the hydrochloride salt to free amine, and then was N-formylated. The N-formylglucosamine was peracetylated with acetic anhydride and the product was dehydrated to give 2-glucosamine isocyanide, which was isolated and purified for the labelling reaction. Cyanide abstraction at the 2-position with freshly made tributyltin deuteride in benzene at 80oC for 2 hours in the presence of a catalytic amount of AIBN generated tetra-O-acetyl-[2-2H]-deoxyglucose. Analysis by 2H NMR spectroscopy showed 2 deuterium peaks, at 1.5 and 2 ppm. Deacetylation gave the desired [2-2H]-deoxyglucose. With the same procedure tetra-O-benzoyl-[2-2H]-deoxyglucose was prepared, but not debenzoylated, so as to facilitate HPLC analysis. In a different application, the same approach was applied to tryptophan methyl ester to generate the corresponding isocyanide. This reaction is a model for a general approach to the synthesis of a-deuterium or tritium labelled carboxylic acids from amino acids. The deuterium labelling of these compounds is underway and will be completed in the near future.