Design and synthesis of a novel ZB716-d6 as a stable isotopically labeled internal standard. Issue 11 (18th June 2022)

• Record Type: Journal Article
• Authors: Zheng, Shilong; Liu, Jiawang; Kang, Borui; Wang, Guangdi
• Is Part Of: Synthetic communications. Volume 52:Issue 11/12(2022)
• Page Start: 1441
• Page End: 1447
• Publication Date: 2022-06-18
• Subjects: Internal standard -- oral SERD -- stable isotope -- ZB716; Organic compounds -- Synthesis -- Periodicals; Chemistry, Organic; Synthesis; 547.205
• DOI: 10.1080/00397911.2022.2095212
• Languages: English
• ISSNs: 0039-7911

Abstract

Abstract: ZB716 is a synthetic, steroidal, orally active anti-estrogen agent that is under clinical development for the treatment of estrogen receptor (ER)-positive metastatic breast cancer. The stable isotope-labeled ZB716 was required for use as an internal standard in LC-MS/MS assays. Therefore, a novel deuterated ZB716 (ZB716-d6) as an isotopically labeled internal standard was designed and synthesized through a newly developed route, which prepared ZB716-d6 in eight steps from the commercially available deuterium-labeled starting material [ 2 H6 ]pentafluoropentanol. This procedure is very practicable and gives the final compound in good yield (19% total yield) and high purity (D, >99%, chemical purity 98%). At present, ZB716-d6 has been successfully used as an internal standard in clinical bioanalysis. Graphical Abstract: UF0001