SYNTHESIS OF LABELED PRECURSORS

我们更新提案的一个主要目标是开发高效的 在氧化态合成有用前体的途径[ 13C]甲醛。如下所述，我们已经开发出高效的 三个重要的新前兆的产生。第一次使用二乙基 以乙醚为溶剂，我们开发了生成 叔丁基[3C]甲基醚(II)的钾阴离子 一种亲核的甲醛当量。例如，阴离子可以是 用二氧化碳捕获乙醇酸的叔丁基保护衍生物 只需两步反应，总收率可达70%。如图所示 下面，我们开发了一条合成氯[13C]甲基叔丁基的两步路线 乙醚(总收率80%)，可用作亲电剂 甲醛当量。最后，我们处理了阴离子叔丁基 [13C]甲醚与苯二硫醚合成叔丁氧基[13C]甲基 苯硫醚(产率85%)。这种化合物是合成的当量化合物。 并提供了一条直接标记的途径 醛和酮。这些[~(13)C]甲醛的可用性 可以显著缩短合成路线，使其在生物医学上具有重要意义 化合物。例如，叔丁基[13C]甲醚的可用性 使我们能够将合成[13C31甘油]缩短到4步 从13CO.

A major goal of our renewal proposal was to develop efficient routes to synthetically useful precursors at the oxidation state of [ 13C]formaldehyde. As described below, we have developed efficient generation of three important new precursors. First using diethyl ether as a solvent, we have developed conditions for the generation of the potassium anion of t-butyl [ 3C]methyl ether (II) which can act as a nucleophilic formaldehyde equivalent. For example, the anion can be trapped withC02 to yield the t-butyl protected derivative of glycolic acid in just two steps with an overall yield of 70%. As diagrammed below, we have developed a two step route to chloro[13C]methyl t-butyl ether (overall 80% yield) which can serve as an electrophilic formaldehyde equivalent. Finally, we have treated the anion t-butyl [13C]methyl ether with phenyl disulfide to yield t-butoxy [13C]methyl phenyl sulfide (85% yield). This compound is the synthetic equivalent of Corey's dithiane reagent and provide a direct route to labeling aldehydes and ketones. The availability of these [13C]fonnaldehyde can significantly shorten synthetic routes to biornedically important compounds. For example, the availability of t-butyl [13C]methyl ether has allowed us to shorten the synthesis of [13C31glycerol to 4 steps from 13CO.