Design and synthesis of a novel ZB716-d6 as a stable isotopically labeled internal standard

• Published in: Synthetic communications Vol. 52; no. 11-12; pp. 1441 - 1447
• Main Authors: Zheng, Shilong, Liu, Jiawang, Kang, Borui, Wang, Guangdi
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 2022; Taylor & Francis Ltd
• Subjects: Deuteration; Deuterium; Estrogens; Internal standard; oral SERD; Purity; stable isotope; ZB716; stable isotope; oral SERD; Internal standard; ZB716
• ISSN: 0039-7911; 1532-2432
• DOI: 10.1080/00397911.2022.2095212

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 H 6 ]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.