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Radiolabeling by trifluoromethyl group is an attractive method to synthesize a useful PET probe. Recently, Haskali et al. have developed the synthetic method of [11C]fluoroform from [11C]CH4 with a CoF3 column and the application route of [11C]fluoroform for various trifluoromethylation reactions [1]. However, those application reactions were not automated and the synthesis of [11C]CF3-aryl derivatives is difficult because preparation of [11C]CuCF3 as a trifluoromethylation reagent was conducted in a glove box to avoid air and moisture. Herein, we developed a synthetic method of [11C]CF3-aryl derivatives using a fully-automated system equipped with [11C]CuCF3 without glove box.\nMethods: [11C]Trifluoromethylation of aryl precursor was performed by using a fully-automated synthesis system (Scheme 1). [11C]Fluoroform was produced by passing [11C]CH4 through a column that was precoated with cobalt(III) fluoride (24 g) and heated at 350 oC. CuOtBu was generated by mixing t-BuOK (15 mol) with CuBr (5 mol) in DMF (0.3 mL) in a sealed vial under N2. Preparation of [11C]CuCF3 was performed by bubbling [11C]fluoroform into the CuOtBu solution at -45 oC. After the radioactivity of [11C]fluoroform reached a plateau, the reaction mixture was warmed to room temperature for 2 min and then added Et3N-3HF (0.82 L) in DMF (0.2 mL). The trifluoromethylation was performed by the reaction of [11C]CuCF3 with aryl precursor (10 mg) at room temperature or 130 oC for 5 min. After the preparative HPLC mobile phase (1.0 mL) was added, the reaction mixture was applied to the HPLC system for separation. The HPLC fraction of [11C]1 was directly collected in a vial. The radioactive product was analyzed by HPLC with radioactivity and UV-VIS detectors. \n\n \nScheme 1. Preparation of [11C]CuCF3 and synthesis of [11C]CF3-aryl derivatives\n\nResults: We prepared CuOtBu without a glove box by carefully treating the all reaction reagents under N2. Reaction of aryl precursor and [11C]CuCF3 did not proceed because HF that was produced by the decomposition of CoF3 prevented the [11C]trifluoromethylation reaction. To solve this problem, we tested various Sep-Pak cartridges to trap HF. Of them, silica plus Sep-Pak cartridge completely removed HF. When using aryl boronic acid as a precursor, [11C]1 was synthesized in 3 ± 1% (n = 5) radiochemical yield from [11C]CH4 at the end of irradiation, with \u003e 99% radiochemical purity. The average total synthesis time from the end of bombardment was 35 min.. On the other hand, when using aryl iodide as a precursor, [11C]1 was only obtained in trace amount. The application scope of [11C]trifluoromethylation is under investigation.\n\nConclusions: We succeeded in the [11C]trifluoromethylation of aryl precursors with [11C]CuCF3 using a full-automated system. We are currently optimizing reaction conditions to improve the radiochemical yield of [11C]1.\nAcknowledgements: This research is supported by QST President’s Strategic Grant Exploratory Research.\n", "subitem_description_type": "Abstract"}]}, "item_10003_publisher_8": {"attribute_name": "出版者", "attribute_value_mlt": [{"subitem_publisher": "Elsevier Ltd."}]}, "item_10003_source_id_9": {"attribute_name": "ISSN", "attribute_value_mlt": [{"subitem_source_identifier": "0969-8051", "subitem_source_identifier_type": "ISSN"}]}, "item_access_right": {"attribute_name": "アクセス権", "attribute_value_mlt": [{"subitem_access_right": "metadata only access", "subitem_access_right_uri": "http://purl.org/coar/access_right/c_14cb"}]}, "item_creator": {"attribute_name": "著者", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "Masayuki, Fujinaga"}], "nameIdentifiers": [{"nameIdentifier": "1055381", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Masanao, Ogawa"}], "nameIdentifiers": [{"nameIdentifier": "1055382", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Nobuki, Nengaki"}], "nameIdentifiers": [{"nameIdentifier": "1055383", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Katsushi, Kumata"}], "nameIdentifiers": [{"nameIdentifier": "1055384", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Wakana, Mori"}], "nameIdentifiers": [{"nameIdentifier": "1055385", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Zhang, Ming-Rong"}], "nameIdentifiers": [{"nameIdentifier": "1055386", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Masayuki, Fujinaga", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "1055387", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Masanao, Ogawa", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "1055388", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Nobuki, Nengaki", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "1055389", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Katsushi, Kumata", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "1055390", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Wakana, Mori", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "1055391", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Zhang, Ming-Rong", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "1055392", "nameIdentifierScheme": "WEKO"}]}]}, "item_language": {"attribute_name": "言語", "attribute_value_mlt": [{"subitem_language": "eng"}]}, "item_resource_type": {"attribute_name": "資源タイプ", "attribute_value_mlt": [{"resourcetype": "conference paper", "resourceuri": "http://purl.org/coar/resource_type/c_5794"}]}, "item_title": "The fully-automated synthesis of [11C]CF3-aryl derivatives with [11C]fluoroform", "item_titles": {"attribute_name": "タイトル", "attribute_value_mlt": [{"subitem_title": "The fully-automated synthesis of [11C]CF3-aryl derivatives with [11C]fluoroform"}]}, "item_type_id": "10003", "owner": "1", "path": ["2"], "permalink_uri": "https://repo.qst.go.jp/records/86453", "pubdate": {"attribute_name": "公開日", "attribute_value": "2022-05-06"}, "publish_date": "2022-05-06", "publish_status": "0", "recid": "86453", "relation": {}, "relation_version_is_last": true, "title": ["The fully-automated synthesis of [11C]CF3-aryl derivatives with [11C]fluoroform"], "weko_shared_id": -1}
The fully-automated synthesis of [11C]CF3-aryl derivatives with [11C]fluoroform
https://repo.qst.go.jp/records/86453
https://repo.qst.go.jp/records/8645381c9dc14-ca99-4b83-a890-9b6f8f9955ec
Item type | 会議発表論文 / Conference Paper(1) | |||||
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公開日 | 2022-05-06 | |||||
タイトル | ||||||
タイトル | The fully-automated synthesis of [11C]CF3-aryl derivatives with [11C]fluoroform | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_5794 | |||||
資源タイプ | conference paper | |||||
アクセス権 | ||||||
アクセス権 | metadata only access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
著者 |
Masayuki, Fujinaga
× Masayuki, Fujinaga× Masanao, Ogawa× Nobuki, Nengaki× Katsushi, Kumata× Wakana, Mori× Zhang, Ming-Rong× Masayuki, Fujinaga× Masanao, Ogawa× Nobuki, Nengaki× Katsushi, Kumata× Wakana, Mori× Zhang, Ming-Rong |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Objectives: The trifluoromethyl group can improve physicochemical properties, such as metabolic stability, lipophilicity and pharmacokinetics of targeted probes. Radiolabeling by trifluoromethyl group is an attractive method to synthesize a useful PET probe. Recently, Haskali et al. have developed the synthetic method of [11C]fluoroform from [11C]CH4 with a CoF3 column and the application route of [11C]fluoroform for various trifluoromethylation reactions [1]. However, those application reactions were not automated and the synthesis of [11C]CF3-aryl derivatives is difficult because preparation of [11C]CuCF3 as a trifluoromethylation reagent was conducted in a glove box to avoid air and moisture. Herein, we developed a synthetic method of [11C]CF3-aryl derivatives using a fully-automated system equipped with [11C]CuCF3 without glove box. Methods: [11C]Trifluoromethylation of aryl precursor was performed by using a fully-automated synthesis system (Scheme 1). [11C]Fluoroform was produced by passing [11C]CH4 through a column that was precoated with cobalt(III) fluoride (24 g) and heated at 350 oC. CuOtBu was generated by mixing t-BuOK (15 mol) with CuBr (5 mol) in DMF (0.3 mL) in a sealed vial under N2. Preparation of [11C]CuCF3 was performed by bubbling [11C]fluoroform into the CuOtBu solution at -45 oC. After the radioactivity of [11C]fluoroform reached a plateau, the reaction mixture was warmed to room temperature for 2 min and then added Et3N-3HF (0.82 L) in DMF (0.2 mL). The trifluoromethylation was performed by the reaction of [11C]CuCF3 with aryl precursor (10 mg) at room temperature or 130 oC for 5 min. After the preparative HPLC mobile phase (1.0 mL) was added, the reaction mixture was applied to the HPLC system for separation. The HPLC fraction of [11C]1 was directly collected in a vial. The radioactive product was analyzed by HPLC with radioactivity and UV-VIS detectors. Scheme 1. Preparation of [11C]CuCF3 and synthesis of [11C]CF3-aryl derivatives Results: We prepared CuOtBu without a glove box by carefully treating the all reaction reagents under N2. Reaction of aryl precursor and [11C]CuCF3 did not proceed because HF that was produced by the decomposition of CoF3 prevented the [11C]trifluoromethylation reaction. To solve this problem, we tested various Sep-Pak cartridges to trap HF. Of them, silica plus Sep-Pak cartridge completely removed HF. When using aryl boronic acid as a precursor, [11C]1 was synthesized in 3 ± 1% (n = 5) radiochemical yield from [11C]CH4 at the end of irradiation, with > 99% radiochemical purity. The average total synthesis time from the end of bombardment was 35 min.. On the other hand, when using aryl iodide as a precursor, [11C]1 was only obtained in trace amount. The application scope of [11C]trifluoromethylation is under investigation. Conclusions: We succeeded in the [11C]trifluoromethylation of aryl precursors with [11C]CuCF3 using a full-automated system. We are currently optimizing reaction conditions to improve the radiochemical yield of [11C]1. Acknowledgements: This research is supported by QST President’s Strategic Grant Exploratory Research. |
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書誌情報 |
Nuclear Medicine and Biology 発行日 2022-06 |
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出版者 | ||||||
出版者 | Elsevier Ltd. | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 0969-8051 |