Chemistry-Switzerland最新文献

筛选

英文中文

The Non-Anhydrous, Minimally Basic Synthesis of the Dopamine D₂ Agonist [18F]MCL-524. 多巴胺D2激动剂[18F]MCL-524的非无水、最低碱性合成。

IF 2.1

Chemistry-Switzerland Pub Date : 2021-09-01 Epub Date: 2021-09-09 DOI: 10.3390/chemistry3030075

James A H Inkster, Anna W Sromek, Vamsidhar Akurathi, John L Neumeyer, Alan B Packard

{"title":"The Non-Anhydrous, Minimally Basic Synthesis of the Dopamine D2 Agonist [18F]MCL-524.","authors":"James A H Inkster, Anna W Sromek, Vamsidhar Akurathi, John L Neumeyer, Alan B Packard","doi":"10.3390/chemistry3030075","DOIUrl":"10.3390/chemistry3030075","url":null,"abstract":"The dopamine D2 agonist MCL-524 is selective for the D2 receptor in the high-affinity state (D2high), and, therefore, the PET analogue, [18F]MCL-524, may facilitate the elucidation of the role of D2high in disorders such as schizophrenia. However, the previously reported synthesis of [18F]MCL-524 proved difficult to replicate and was lacking experimental details. We therefore developed a new synthesis of [18F]MCL-524 using a \"non-anhydrous, minimally basic\" (NAMB) approach. In this method, [18F]F- is eluted from a small (10-12 mg) trap-and-release column with tetraethylammonium tosylate (2.37 mg) in 7:3 MeCN:H2O (0.1 mL), rather than the basic carbonate or bicarbonate solution that is most often used for [18F]F- recovery. The tosylated precursor (1 mg) in 0.9 mL anhydrous acetonitrile was added directly to the eluate, without azeotropic drying, and the solution was heated (150 °C/15 min). The catechol was then deprotected with the Lewis acid In(OTf)3 (10 equiv.; 150 °C/20 min). In contrast to deprotection with protic acids, Lewis-acid-based deprotection facilitated the efficient removal of byproducts by HPLC and eliminated the need for SPE extraction prior to HPLC purification. Using the NAMB approach, [18F]MCL-524 was obtained in 5-9% RCY (decay-corrected, n = 3), confirming the utility of this improved method for the multistep synthesis of [18F]MCL-524 and suggesting that it may applicable to the synthesis of other 18F-labeled radiotracers.","PeriodicalId":53216,"journal":{"name":"Chemistry-Switzerland","volume":"3 3","pages":"1047-1056"},"PeriodicalIF":2.1,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10569134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41219982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0