{"id":35279,"date":"2020-10-06T08:00:44","date_gmt":"2020-10-06T00:00:44","guid":{"rendered":"\/\/www.gsbet888.com\/?p=35279"},"modified":"2020-10-01T14:43:02","modified_gmt":"2020-10-01T06:43:02","slug":"nature%e5%ad%90%e5%88%8a%ef%bc%9a%e8%8a%b3%e5%9f%ba%e5%94%91%e7%9a%84%e5%8c%ba%e5%9f%9f%e9%80%89%e6%8b%a9%e6%80%a7%e5%8a%9f%e8%83%bd%e5%8c%96","status":"publish","type":"post","link":"\/\/www.gsbet888.com\/%e5%8c%96%e5%ad%a6%e6%9d%82%e8%ae%b0\/recentpaper\/2020\/10\/nature%e5%ad%90%e5%88%8a%ef%bc%9a%e8%8a%b3%e5%9f%ba%e5%94%91%e7%9a%84%e5%8c%ba%e5%9f%9f%e9%80%89%e6%8b%a9%e6%80%a7%e5%8a%9f%e8%83%bd%e5%8c%96.html","title":{"rendered":"Nature\u5b50\u520a\uff1a\u82b3\u57fa\u5511\u7684\u533a\u57df\u9009\u62e9\u6027\u529f\u80fd\u5316"},"content":{"rendered":"

\u672c\u6587\u4f5c\u8005\uff1a\u6749\u6749<\/p>\n

\u5bfc\u8bfb<\/strong><\/h4>\n

N<\/em>-\u82b3\u57fa\u5511\u9aa8\u67b6\uff08Aryl azole\uff09\u5e7f\u6cdb\u5b58\u5728\u5404\u7c7b\u836f\u7269\u5206\u5b50\u4e2d\uff0c\u7531\u4e8e\u9178\u6027\u7684\u6742\u73af\u5177\u6709\u7ade\u4e89\u6027\u7684\u91d1\u5c5e\u5316\u4f5c\u7528\uff08metalation\uff09\uff0c\u5bfc\u81f4\u82b3\u73af\u4e0a\u7684\u90bb\u4f4d\u9009\u62e9\u6027\u91d1\u5c5e\u5316\u6781\u5177\u6311\u6218\u3002\u4e3a\u4e86\u5f00\u53d1\u4e00\u79cd\u5173\u952e\u6d3b\u6027\u836f\u7269\u6210\u5206\uff08API\uff09\u4e2d\u95f4\u4f53\u7684\u5b9e\u7528\u9014\u5f84\uff0c\u4f5c\u8005\u7814\u7a76\u4e86\u5177\u6709\u7a7a\u95f4\u4f4d\u963b\u7684\u91d1\u5c5e\u9170\u80fa\u78b1\uff08metal-amide bases\uff09\u4e0e1-\u82b3\u57fa-1H<\/em>-1,2,3-\u4e09\u5511\u548c\u5176\u5b83\u6742\u73af\u7684\u91d1\u5c5e\u5316\u4f5c\u7528\u3002\u5728\u6b64\uff0c\u5fb7\u56fd\u6155\u5c3c\u9ed1\u5927\u5b66Paul Knochel\u6559\u6388\u4e0e\u745e\u58eb\u6768\u68ee\u5236\u836f\u516c\u53f8\uff08Janssen Pharmaceutica\uff09Simon Wagschal\u5171\u540c\u5728Nature Communications<\/em>\u4e0a\u62a5\u9053\u4e86\uff0c\u53ef\u5728\u5ba4\u6e29\u6761\u4ef6\u4e0b\uff0c\u70c3\u7c7b\u6eb6\u5242\u4e2d\u4f7f\u7528\u6c28\u57fa\u5316\u9541\uff08magnesium amide\uff0cTMPMgBu\uff08TMP = 2,2,6,6-\u56db\u7532\u57fa\u54cc\u5576\u57fa\uff09\uff0c\u5b9e\u73b0\u5bf9\u51e0\u79cd\u82b3\u57fa\u5511\u7684\u9ad8\u5ea6\u533a\u57df\u9009\u62e9\u6027\u7684\u90bb\u4f4d\u91d1\u5c5e\u5316\uff0c\u7136\u540e\u6709\u6548\u8fdb\u884c\u4e86Pd\u50ac\u5316\u7684\u82b3\u57fa\u5316\u53cd\u5e94\u3002\u8fd9\u79cd\u53ef\u6269\u5c55\u548c\u9009\u62e9\u6027\u7684\u53cd\u5e94\u5141\u8bb8\u6539\u53d8\u82b3\u57fa\u73af\u7684\u53d6\u4ee3\u6a21\u5f0f\uff0c\u5511\u90e8\u5206\u7684\u6027\u8d28\u4ee5\u53ca\u4eb2\u7535\u8bd5\u5242\u7684\u6027\u8d28\u3002\u8fd9\u79cd\u901a\u7528\u7684\u65b9\u6cd5\u53ef\u4ee5\u5e94\u7528\u4e8e\u751f\u7269\u6d3b\u6027\u5511\u884d\u751f\u7269\u7684\u5408\u6210\uff0c\u5e76\u8865\u5145\u73b0\u6709\u7684\u91d1\u5c5e\u4ecb\u5bfc\u7684\u90bb\u4f4d\u5b98\u80fd\u5316\u53cd\u5e94\u3002<\/p>\n

Regioselective functionalization of aryl azoles aspowerful tool for the synthesis of pharmaceutically relevant targets<\/p>\n

Ferdinand H. Lutter, Lucie Grokenberger, Luca Alessandro Perego , Diego Broggini,<\/p>\n

S\u00e9bastienLemaire, Simon Wagschal& Paul Knochel<\/p>\n

Nat. Commu. <\/em>ASAP DOI:10.1038\/s41467-020-18188-z<\/a><\/p><\/blockquote>\n

\"\"<\/a><\/p>\n

\u524d\u8a00<\/strong><\/h4>\n

N<\/em>-\u82b3\u57fa\u5511\u9aa8\u67b6\u5b58\u5728\u4e8e\u591a\u79cd\u5e02\u552e\u7684\u836f\u7269\u4e2d\uff0c\u5982\u585e\u6765\u6614\u5e03\uff08celecoxib\uff09\u3001\u963f\u54cc\u6c99\u73ed\uff08apixaban\uff09\u3001\u9f50\u6cca\u817e\u5766\uff08zibotentan\uff09\u548c\u5948\u6c99\u5730\u5c14\uff08nesapidil\uff09\uff08Fig. 1a\uff09\u3002\u82e5\u76f4\u63a5\u5b9e\u73b01-\u82b3\u57fa-1H<\/em>-1,2,3-\u4e09\u5511\uff082a<\/strong>\uff09\u7684\u90bb\u4f4dC-H\u529f\u80fd\u5316\uff0c\u5219\u53ef\u76f4\u63a5\u83b7\u76ee\u6807\u4ea7\u72691a<\/strong>\uff08Fig. 1b\uff09\u3002\u5bf9\u4e8e\u6d89\u53ca\u8fc7\u6e21\u91d1\u5c5e\u50ac\u5316\u7684C-H\u82b3\u57fa\u5316\u7684\u65b9\u6cd5\uff0c\u5e38\u9700\u82db\u523b\u7684\u6761\u4ef6\uff0c\u5e76\u4ea7\u751f\u53cc\u82b3\u57fa\u5316\u4ea7\u7269\uff0c\u4ece\u800c\u9650\u5236\u4e86\u5b83\u4eec\u7684\u5b9e\u7528\u6027\u3002\u56e0\u6b64\uff0c\u4f7f\u7528\u5408\u9002\u7684\u78b1\u76f4\u63a5\u53bb\u8d28\u5b50\u5316\uff0c\u662f\u82b3\u57fa\u5511\u9009\u62e9\u6027\u5b98\u80fd\u5316\u7684\u66ff\u4ee3\u65b9\u6848\u3002\u7136\u800c\uff0c\u7531\u4e8eN<\/em>-\u6742\u73af\u672c\u8eab\u5177\u6709\u7ade\u4e89\u6027\u7684\u91d1\u5c5e\u5316\u4f5c\u7528\uff0c\u4e0e\u6742\u73af\u76f8\u8fde\u7684\u82b3\u57fa\u73af\u7684\u533a\u57df\u9009\u62e9\u6027\u91d1\u5c5e\u5316\u6781\u5177\u6311\u6218\u3002<\/p>\n

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\u6b64\u5916\uff0c\u4f5c\u8005\u8fd8\u5c06\u82b3\u57fa\u9541\u8bd5\u52423a<\/strong>\u4e0e\u5176\u5b83\u5e38\u89c1\u7684\u4eb2\u7535\u8bd5\u5242\u53cd\u5e94\uff08Fig. 4b\uff09\u3002\u82e5\u4e0eI2<\/sub>\u53cd\u5e94\u83b7\u5f9798\uff05\u6536\u7387\u76847a<\/strong>\u3002\u82e5\u4e0e\u82ef\u7532\u919b\u6216MeSSO2<\/sub>Me\uff0c\u5206\u522b\u4ee586\uff05\u548c75\uff05\u7684\u4ea7\u7387\u5f97\u5230\u76f8\u5e94\u7684\u91877b<\/strong>\u6216\u786b\u919a7c<\/strong>\u3002\u82e5\u7528CuCN\u22c52LiCl\u8fdb\u884c\u91d1\u5c5e\u8f6c\u79fb\uff0c\u7136\u540e\u4e0e\u82ef\u7532\u9170\u6c2f\u6216\u70ef\u4e19\u57fa\u6eb4\u884d\u751f\u7269\u53cd\u5e94\uff0c\u5f97\u52307d<\/strong>–7e<\/strong>\uff0c\u4ea7\u7387\u4e3a62-77\uff05\u3002<\/p>\n

\"\"<\/a><\/p>\n

\"\"<\/a><\/p>\n

\u540e\u671f\u4fee\u9970<\/strong><\/span><\/p>\n

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\"\"<\/a><\/p>\n

\u53cd\u5e94\u673a\u7406<\/strong><\/span><\/p>\n

\u4e3a\u4e86\u8fdb\u4e00\u6b65\u4e86\u89e3\u53cd\u5e94\u7684\u673a\u7406\uff0c\u4f5c\u8005\u8fdb\u884c\u4e86\u76f8\u5173\u7684\u5bf9\u7167\u5b9e\u9a8c\uff08Fig. 6\uff09\u3002\u5df2\u77e5\u5e02\u552e\u7684Bu2<\/sub>Mg\u6eb6\u6db2\uff08\u6b63\u4e01\u57fa\u548c\u4ef2\u4e01\u57fa\u7684\u6bd4\u4f8b\u4e3a6:4\uff09\uff0c\u800c\u5728TMPMgBu\u4e2d\u7684\u4e24\u8005\u6bd4\u4f8b\u76f8\u540c\u3002\u5f53\u5728\u7532\u82ef\/\u5df1\u70f7\u4e2d\uff0cBu2<\/sub>Mg\u4e5f\u662f\u9009\u62e9\u6027\u8131\u8d28\u5b50\u53162a<\/strong>\u7684\u6781\u597d\u78b1\uff0893\uff05\u4ea7\u7387\uff09\uff0c\u6240\u5f97\u6df7\u5408\u7269\u4e3b\u8981\u5305\u542bArMg(n<\/em>-Bu)\u548cArMg(s<\/em>-Bu)\uff08\u5206\u522b\u4e3a89\uff05\u548c4\uff05\uff09\u3002\u7136\u800c\uff0c\u5728\u7528\u6c2f\u5316\u950c\u8fdb\u884c\u91d1\u5c5e\u8f6c\u79fb\u540e\uff0c\u7531\u4e8e\u6b63\u4e01\u57fa\u7684\u4ea4\u53c9\u5076\u8054\uff0c\u4ec5\u83b7\u5f97\u4e8628\uff05\u7684\u6240\u9700\u4ea4\u53c9\u5076\u8054\u4ea7\u72691b<\/strong>\u548c88\uff05\u76844-\u4e01\u57fa\u8334\u9999\u919a\uff0813a<\/strong>\uff09\u3002\u8be5\u7ed3\u679c\u8bf4\u660e\uff0c\u5728\u91d1\u5c5e\u5316\/\u4ea4\u53c9\u5076\u8054\u7684\u8fc7\u7a0b\u4e2d\uff0cTMPMgBu\u4f18\u4e8eBu2<\/sub>Mg\uff0cTMPMgBu\u7684\u4f7f\u7528\u9650\u5236\u4e86ArMgBu\u7684\u5f62\u6210\uff0c\u56e0\u6b64\u5728ArZnBu\u91cd\u91d1\u5c5e\u5316\u540e\u4f18\u5148\u5c06\u4e01\u57fa\u8f6c\u79fb\u81f3Ar’Br\uff0c\u5f62\u6210\u526f\u4ea7\u7269Ar’Bu\uff0813a<\/strong>\uff09\u3002<\/p>\n

\"\"<\/a><\/p>\n

\u603b\u7ed3<\/strong><\/h4>\n

\u672c\u6587\u4e3b\u8981\u63cf\u8ff0\u4e86\uff0c\u53ef\u5728\u5ba4\u6e29\u6761\u4ef6\u4e0b\uff0c\u5728\u70c3\u7c7b\u6eb6\u5242\u4e2d\u4f7f\u7528\u6c28\u57fa\u5316\u9541\uff08TMPMgBu\uff09\uff0c\u53ef\u5b9e\u73b0\u5bf9\u51e0\u79cd\u82b3\u57fa\u5511\u7684\u9ad8\u5ea6\u533a\u57df\u9009\u62e9\u6027\u7684\u90bb\u4f4d\u91d1\u5c5e\u5316\uff0c\u7136\u540e\u5728\u94af\u50ac\u5316\u53ef\u4e0e\u591a\u79cd\uff08\u6742\uff09\u82b3\u57fa\u6eb4\u5316\u7269\u6216\u4eb2\u7535\u8bd5\u5242\u8fdb\u884c\u82b3\u57fa\u5316\u53cd\u5e94\u3002\u540c\u65f6\uff0c\u8be5\u65b9\u6cd5\u5b66\u53ef\u4ee5\u5e94\u7528\u4e8e\u5173\u952eAPI\u4e2d\u95f4\u4f53\u7684\u5408\u6210\uff0c\u5e76\u4e14\u4ea7\u7269\u7684\u540e\u671f\u4fee\u9970\u8fdb\u4e00\u6b65\u8bc1\u660e\u4e86\u53cd\u5e94\u7684\u5b9e\u7528\u6027\u3002<\/p>\n

\u672c\u6587\u7248\u6743\u5c5e\u4e8e\u00a0Chem-Station\u5316\u5b66\u7a7a\u95f4<\/a>\uff0c<\/strong>\u00a0\u6b22\u8fce\u70b9\u51fb\u6309\u94ae\u5206\u4eab\uff0c\u672a\u7ecf\u8bb8\u53ef\uff0c\u8c22\u7edd\u8f6c\u8f7d\uff01<\/p>\n","protected":false},"excerpt":{"rendered":"\u672c\u6587\u4f5c\u8005\uff1a\u6749\u6749 \u5bfc\u8bfb N-\u82b3\u57fa\u5511\u9aa8\u67b6\uff08Aryl azole\uff09\u5e7f\u6cdb\u5b58\u5728\u5404\u7c7b\u836f\u7269\u5206\u5b50\u4e2d\uff0c\u7531\u4e8e\u9178\u6027\u7684\u6742\u73af\u5177\u6709\u7ade\u4e89\u6027\u7684\u91d1\u5c5e\u5316\u4f5c\u7528\uff08metalation\uff09\uff0c\u5bfc\u81f4\u82b3\u73af\u4e0a\u7684\u90bb\u4f4d\u9009\u62e9\u6027\u91d1\u5c5e\u5316\u6781\u5177\u6311\u6218\u3002\u4e3a\u4e86\u5f00\u53d1\u4e00\u79cd\u5173\u952e\u6d3b\u6027\u836f\u7269\u6210\u5206\uff08API\uff09\u4e2d\u95f4\u4f53\u7684\u5b9e\u7528\u9014\u5f84\uff0c\u4f5c\u8005\u7814\u7a76\u4e86\u5177\u6709\u7a7a\u95f4\u4f4d\u963b\u7684\u91d1\u5c5e\u9170\u80fa\u78b1\uff08metal-amide bases\uff09\u4e0e1-\u82b3\u57fa-1H-1,2,3-\u4e09\u5511\u548c\u5176\u5b83\u6742\u73af\u7684\u91d1\u5c5e\u5316\u4f5c\u7528\u3002\u5728\u6b64\uff0c\u5fb7\u56fd\u6155\u5c3c\u9ed1\u5927\u5b66Paul Knochel\u6559\u6388\u4e0e\u745e\u58eb\u6768\u68ee\u5236\u836f\u516c\u53f8\uff08Janssen Pharmaceutica\uff09Simon Wagschal\u5171\u540c\u5728Nature Communications\u4e0a\u62a5\u9053\u4e86\uff0c\u53ef\u5728\u5ba4\u6e29\u6761\u4ef6\u4e0b\uff0c\u70c3\u7c7b\u6eb6\u5242\u4e2d\u4f7f\u7528\u6c28\u57fa\u5316\u9541\uff08magnesium amide\uff0cTMPMgBu\uff08TMP = 2,2,6,6-\u56db\u7532\u57fa\u54cc\u5576\u57fa\uff09\uff0c\u5b9e\u73b0\u5bf9\u51e0\u79cd\u82b3\u57fa\u5511\u7684\u9ad8\u5ea6\u533a\u57df\u9009\u62e9\u6027\u7684\u90bb\u4f4d\u91d1\u5c5e\u5316\uff0c\u7136\u540e\u6709\u6548\u8fdb\u884c\u4e86Pd\u50ac\u5316\u7684\u82b3\u57fa\u5316\u53cd\u5e94\u3002\u8fd9\u79cd\u53ef\u6269\u5c55\u548c\u9009\u62e9\u6027\u7684\u53cd\u5e94\u5141\u8bb8\u6539\u53d8\u82b3\u57fa\u73af\u7684\u53d6\u4ee3\u6a21\u5f0f\uff0c\u5511\u90e8\u5206\u7684\u6027\u8d28\u4ee5\u53ca\u4eb2\u7535\u8bd5\u5242\u7684\u6027\u8d28\u3002\u8fd9\u79cd\u901a\u7528\u7684\u65b9\u6cd5\u53ef\u4ee5\u5e94\u7528\u4e8e\u751f\u7269\u6d3b\u6027\u5511\u884d\u751f\u7269\u7684\u5408\u6210\uff0c\u5e76\u8865\u5145\u73b0\u6709\u7684\u91d1\u5c5e\u4ecb\u5bfc\u7684\u90bb\u4f4d\u5b98\u80fd\u5316\u53cd\u5e94\u3002 Regioselective functionalization of aryl azoles aspowerful tool for the synthesis of pharmaceutically relevant targets Ferdinand H. Lutter, Lucie Grokenberger, Luca Alessandro Perego , Diego Broggini, S\u00e9bastienLemaire, Simon Wagschal& Paul Knochel Nat. Commu. ASAP DOI:10.1038\/s41467-020-18188-z \u524d\u8a00 N-\u82b3\u57fa\u5511\u9aa8\u67b6\u5b58\u5728\u4e8e\u591a\u79cd\u5e02\u552e\u7684\u836f\u7269\u4e2d\uff0c\u5982\u585e\u6765\u6614\u5e03\uff08celecoxib\uff09\u3001\u963f\u54cc\u6c99\u73ed\uff08apixaban\uff09\u3001\u9f50\u6cca\u817e\u5766\uff08zibotentan\uff09\u548c\u5948\u6c99\u5730\u5c14\uff08nesapidil\uff09\uff08Fig. 1a\uff09\u3002\u82e5\u76f4\u63a5\u5b9e\u73b01-\u82b3\u57fa-1H-1,2,3-\u4e09\u5511\uff082a\uff09\u7684\u90bb\u4f4dC-H\u529f\u80fd\u5316\uff0c\u5219\u53ef\u76f4\u63a5\u83b7\u76ee\u6807\u4ea7\u72691a\uff08Fig. 1b\uff09\u3002\u5bf9\u4e8e\u6d89\u53ca\u8fc7\u6e21\u91d1\u5c5e\u50ac\u5316\u7684C-H\u82b3\u57fa\u5316\u7684\u65b9\u6cd5\uff0c\u5e38\u9700\u82db\u523b\u7684\u6761\u4ef6\uff0c\u5e76\u4ea7\u751f\u53cc\u82b3\u57fa\u5316\u4ea7\u7269\uff0c\u4ece\u800c\u9650\u5236\u4e86\u5b83\u4eec\u7684\u5b9e\u7528\u6027\u3002\u56e0\u6b64\uff0c\u4f7f\u7528\u5408\u9002\u7684\u78b1\u76f4\u63a5\u53bb\u8d28\u5b50\u5316\uff0c\u662f\u82b3\u57fa\u5511\u9009\u62e9\u6027\u5b98\u80fd\u5316\u7684\u66ff\u4ee3\u65b9\u6848\u3002\u7136\u800c\uff0c\u7531\u4e8eN-\u6742\u73af\u672c\u8eab\u5177\u6709\u7ade\u4e89\u6027\u7684\u91d1\u5c5e\u5316\u4f5c\u7528\uff0c\u4e0e\u6742\u73af\u76f8\u8fde\u7684\u82b3\u57fa\u73af\u7684\u533a\u57df\u9009\u62e9\u6027\u91d1\u5c5e\u5316\u6781\u5177\u6311\u6218\u3002 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bases\uff09\u4e2d\uff0c\u5c24\u5176\u662f\u9541\u548c\u950c\u884d\u751f\u7684TMP\u78b1\u4f5c\u4e3a\u5404\u79cd\uff08\u6742\uff09\u82b3\u70c3\u5b98\u80fd\u5316\u7684\u6709\u6548\u8bd5\u5242\uff0c\u8d8a\u6765\u8d8a\u88ab\u91cd\u89c6\u3002Hagadorn\u62a5\u9053\uff0cTMP2Zn\u662f\u5404\u79cd\u7fb0\u57fa\u5316\u5408\u7269\u7684\u03b1-\u950c\u79bb\u5b50\u5316\u53cd\u5e94\u548c\u5421\u5576-N-\u6c27\u5316\u7269\u5728\u7532\u82ef\u4e2d\u91d1\u5c5e\u5316\u53cd\u5e94\u7684\u6700\u4f73\u78b1\u3002\u540c\u6837\uff0cMulvey\u8bfe\u9898\u7ec4\u62a5\u9053\u4e86\u51e0\u79cd\u5728\u975e\u914d\u4f4d\u70c3\u6eb6\u5242\u4e2d\uff0c\u7528\u4e8e\u91d1\u5c5e\u5316\u53cd\u5e94\u7684\u6df7\u5408\u53cc\u91d1\u5c5e\u9170\u80fa\u78b1\u3002\u5728\u6b64\uff0c\u5fb7\u56fd\u6155\u5c3c\u9ed1\u5927\u5b66Paul Knochel\u6559\u6388\u4e0e\u745e\u58eb\u6768\u68ee\u5236\u836f\u516c\u53f8Simon 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