SYNTHESIS OF STABLE ISOTOPE-LABELED STEROIDS FOR THE MEASUREMENT OF ENDOGENOUS S

这份SBIR第二阶段提案详细阐述了在第一阶段取得的成功，在这一阶段，IsoSciences成功地开发了1)区域选择性制备2和4-甲氧基-[13C，2H3]标记雌激素和2)制备睾酮-[1，2，3-13C3]的合成方法。 第一阶段开发的方法将在第二阶段扩大规模，使IsoSciences，LLC将生产100毫克数量的几种稳定同位素标记的关键类固醇激素，包括2-、3-和4-甲氧基雌激素、雌三醇、睾酮、雌酮、雌二醇、雄烯二酮和脱氢表雄酮。选定的化合物被认为在各种癌症中发挥关键作用，因此有可能作为癌症生物标记物。研究领域的一个重大障碍是缺乏用于检测和量化这些关键类固醇的稳定同位素标记标准。这份第二阶段合同将解决这一重大问题。

This SBIR Phase II proposal elaborates on the success achieved during Phase I where IsoSciences was successful in developing synthetic methods for 1) The regioselective preparation of 2 and 4-methoxy-[13C,2H3] labeled estrogens and 2) The preparation of testosterone-[1,2,3-13C3]. The methodology developed in Phase I will be scaled up in Phase II such that IsoSciences, LLC will produce 100mg quantities of several stable-isotope labeled key steroid hormones including 2-, 3-, and 4-methoxyestrogens, estriol, testosterone, estrone, estradiol, and androstenedione and dehydroepiandrosterone. The selected compounds are believed to play critical roles in various cancers and thus have the potential to serve as cancer biomarkers. A significant stumbling block in the research area has been the lack of availability of stable isotope labeled standards for use in detecting and quantifying these key steroids. This Phase II contract will address that significant problem.