Gao Mingzhang, Wang Min, Green Mark A, Hutchins Gary D, Zheng Qi-Huang
Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 1345 West 16th Street, Room 202, Indianapolis, IN 46202, USA.
Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 1345 West 16th Street, Room 202, Indianapolis, IN 46202, USA.
Bioorg Med Chem Lett. 2015 May 1;25(9):1965-70. doi: 10.1016/j.bmcl.2015.03.021. Epub 2015 Mar 14.
The authentic standards GSK1482160 and its isomer, as well as the radiolabeling precursors desmethyl-GSK1482160 and Boc-protected desmethyl-GSK1482160 were synthesized from L-pyroglutamic acid, methyl L-pyroglutamate and 2-chloro-3-(trifluoromethyl)benzylamine with overall chemical yield 27-28% in 3 steps, 58% in 4 steps, 76% in 1 step and 33% in 2 steps, respectively. [(11)C]GSK1482160 was prepared from either desmethyl-GSK1482160 or Boc-protected desmethyl-GSK1482160 with [(11)C]CH3OTf through N-[(11)C]methylation and isolated by HPLC combined with SPE in 40-50% and 30-40% radiochemical yield, respectively, based on [(11)C]CO2 and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the specific activity at EOB was 370-1110 GBq/μmol with a total synthesis time of ∼40-min from EOB.
真实标准品GSK1482160及其异构体，以及放射性标记前体去甲基-GSK1482160和Boc保护的去甲基-GSK1482160由L-焦谷氨酸、L-焦谷氨酸甲酯和2-氯-3-(三氟甲基)苄胺合成，三步总化学产率分别为27-28%，四步为58%，一步为76%，两步为33%。[(11)C]GSK1482160由去甲基-GSK1482160或Boc保护的去甲基-GSK1482160与[(11)C]CH3OTf通过N-[(11)C]甲基化制备，并通过HPLC结合SPE分离，基于[(11)C]CO2且校正至轰击结束(EOB)时的放射性化学产率分别为40-50%和30-40%。放射性化学纯度>99%，EOB时的比活度为370-1110 GBq/μmol，从EOB开始的总合成时间约为40分钟。
