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.

我们更新建议的一个主要目标是发展高效的