SYNTHESIS OF LABELED PRECURSORS

我们更新提案的一个主要目标是开发高效的 合成有用的氧化态前体的途径[ 13C]甲醛。 如下文所述，我们开发了高效的 三个重要的前体的产生。 首先使用二乙基 醚作为溶剂，我们已经开发了生成 叔丁基[ 3C]甲基醚（II）的钾阴离子，其可以作为 亲核甲醛等价物。 例如，阴离子可以是 用CO2捕集以产生乙醇酸的叔丁基保护的衍生物 酸，总收率为70%。 如图所示 下面，我们开发了一种两步法合成氯[13C]甲基叔丁基 醚（总收率80%），其可用作亲电剂。 甲醛当量 最后，我们处理了阴离子叔丁基 [13C]甲基醚与苯基二硫化物反应，得到叔丁氧基[13C]甲基 苯硫醚（产率85%）。 这种化合物是人工合成的 的科里的二噻烷试剂，并提供了一个直接的路线标记 醛和酮。 这些[13 C]甲醛的可用性 可以显著缩短合成路线， 化合物. 例如，叔丁基[13 C]甲基醚的可用性 使我们能够将[13C31]甘油的合成缩短为4步 13CO的。

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.