SYNTHESIS OF LABELED PRECURSORS

标记前体的合成

• 批准号: 6309028
• 负责人: RODOLFO MARTINEZ
• 金额: $ 2.74万
• 依托单位: UNIVERSITY OF CALIF-LOS ALAMOS NAT LAB
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-02-01 至 2002-01-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6309028
• 关键词: biological products; biomedical resource; enzymes; nucleic acids

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.

我们更新提案的一个主要目标是开发高效的 在[的氧化态下合成有用的前体的路线 13C]甲醛。 如下所述，我们开发了高效的 产生了三个重要的新先驱。 首先使用二乙基 乙醚作为溶剂，我们开发了生成的条件 叔丁基[3C]甲基醚(II)的钾阴离子，可充当 亲核甲醛等价物。 例如，阴离子可以是 用CO 2 捕集以产生叔丁基保护的乙醇酸衍生物 仅需两步即可得到酸，总产率为70%。 如图所示 下面，我们开发了一种生产氯[13C]甲基叔丁基的两步路线 乙醚（总收率 80%），可作为亲电子试剂 甲醛当量。 最后，我们处理了阴离子叔丁基 [13C]甲基醚与二硫苯基反应生成叔丁氧基[13C]甲基 苯硫醚（85%产率）。 该化合物是合成等效物 Corey 的二噻烷试剂并提供直接标记途径 醛和酮。 这些[13C]甲醛的可用性 可以显着缩短具有生物医学重要性的合成路线 化合物。 例如，叔丁基[13C]甲基醚的可用性 使我们能够将[13C31甘油的合成缩短至4步 来自13CO。