{"id":29374,"date":"2019-11-05T08:10:39","date_gmt":"2019-11-05T00:10:39","guid":{"rendered":"\/\/www.gsbet888.com\/?p=29374"},"modified":"2019-11-11T10:17:25","modified_gmt":"2019-11-11T02:17:25","slug":"%e8%89%be%e6%bb%8b%e7%97%85%e7%9a%84%e9%a6%96%e9%80%89%e8%8d%af%e7%89%a9-%e5%a4%9a%e6%9b%bf%e6%8b%89%e9%9f%a6%ef%bc%88dolutegravir%ef%bc%89","status":"publish","type":"post","link":"\/\/www.gsbet888.com\/molecule\/2019\/11\/%e8%89%be%e6%bb%8b%e7%97%85%e7%9a%84%e9%a6%96%e9%80%89%e8%8d%af%e7%89%a9-%e5%a4%9a%e6%9b%bf%e6%8b%89%e9%9f%a6%ef%bc%88dolutegravir%ef%bc%89.html","title":{"rendered":"\u827e\u6ecb\u75c5\u7684\u9996\u9009\u836f\u7269\u2014\u2014\u591a\u66ff\u62c9\u97e6\uff08Dolutegravir\uff09"},"content":{"rendered":"<h4><strong>\u4e00\u3001\u5f15\u8a00<\/strong><\/h4>\n<p>\u827e\u6ecb\u75c5\u662f\u83b7\u5f97\u6027\u514d\u75ab\u7f3a\u9677\u7efc\u5408\u5f81\uff08Acquired Immune Deficiency 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href=\"https:\/\/assets.www.gsbet888.com\/uploads\/2019\/11\/2-10.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter wp-image-29376 \" src=\"https:\/\/assets.www.gsbet888.com\/uploads\/2019\/11\/2-10.jpg\" alt=\"\" width=\"704\" height=\"470\" srcset=\"https:\/\/assets.www.gsbet888.com\/uploads\/2019\/11\/2-10.jpg 975w, https:\/\/assets.www.gsbet888.com\/uploads\/2019\/11\/2-10-300x200.jpg 300w, https:\/\/assets.www.gsbet888.com\/uploads\/2019\/11\/2-10-768x512.jpg 768w, https:\/\/assets.www.gsbet888.com\/uploads\/2019\/11\/2-10-680x453.jpg 680w\" sizes=\"(max-width: 704px) 100vw, 704px\" \/><\/a><\/p>\n<p style=\"text-align: center;\">\u56fe 2 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href=\"https:\/\/assets.www.gsbet888.com\/uploads\/2019\/11\/3-7.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter wp-image-29377 \" src=\"https:\/\/assets.www.gsbet888.com\/uploads\/2019\/11\/3-7.jpg\" alt=\"\" width=\"790\" height=\"405\" srcset=\"https:\/\/assets.www.gsbet888.com\/uploads\/2019\/11\/3-7.jpg 1196w, https:\/\/assets.www.gsbet888.com\/uploads\/2019\/11\/3-7-300x154.jpg 300w, https:\/\/assets.www.gsbet888.com\/uploads\/2019\/11\/3-7-768x393.jpg 768w, https:\/\/assets.www.gsbet888.com\/uploads\/2019\/11\/3-7-680x348.jpg 680w\" sizes=\"(max-width: 790px) 100vw, 790px\" \/><\/a><\/p>\n<p style=\"text-align: center;\">\u56fe 3 \u6cbb\u7597\u827e\u6ecb\u75c5\u7684\u5e38\u89c1\u836f\u7269<\/p>\n<p>2013\u5e74\u7ecfFDA\u6279\u51c6\uff0c\u62c9\u66ff\u62c9\u97e6\uff08Raltegravir\uff0c\u5546\u54c1\u540d\u4e3a\u827e\u751f\u7279\uff09\u4f5c\u4e3a\u7b2c\u4e00\u4ee3\u6574\u5408\u9176\u6291\u5236\u5242\u8fdb\u5165\u4e34\u5e8a\uff0c\u6cbb\u7597\u6548\u679c\u7a81\u51fa\uff0c\u4e0d\u826f\u53cd\u5e94\u548c\u836f\u7269\u76f8\u4e92\u4f5c\u7528\u90fd\u8f83\u5c11\u3002\u968f\u540e\u53e6\u5916\u4e24\u4e2a\u6574\u5408\u9176\u6291\u5236\u5242\u836f\u7269\u57c3\u66ff\u683c\u97e6\uff08Elvitegravir\uff09\u548c\u591a\u66ff\u62c9\u97e6\uff08Dolutegravir\uff09\u88ab\u6279\u51c6\u4e0a\u5e02\uff0c\u540e\u7eed\u7814\u7a76\u8868\u660e\u591a\u66ff\u62c9\u97e6\u66f4\u4e0d\u6613\u4ea7\u751f\u8010\u836f\u6027\u3002\u56e0\u6b64\uff0c\u5305\u62ec\u7f8e\u56fd\u5728\u5185\u7684\u8bb8\u591a\u533b\u7597\u8d44\u6e90\u4e30\u5bcc\u7684\u53d1\u8fbe\u56fd\u5bb6\u8d8a\u6765\u8d8a\u613f\u610f\u63a8\u8350\u4f7f\u7528\u542b\u6574\u5408\u9176\u6291\u5236\u5242\u7684\u6cbb\u7597\u65b9\u6848\u4f5c\u4e3a\u4e00\u7ebf\u6297\u75c5\u6bd2\u836f\u7269\u30022019\u5e747\u6708\uff0c\u4e16\u536b\u7ec4\u7ec7\u66f4\u662f\u5f3a\u70c8\u5efa\u8bae\u5c06\u591a\u66ff\u62c9\u97e6\u4f5c\u4e3a\u827e\u6ecb\u75c5\u9996\u9009\u6cbb\u7597\u65b9\u6848\u3002<sup>[4]<\/sup><\/p>\n<h4><strong>\u56db\u3001\u591a\u66ff\u62c9\u97e6\u7684\u5408\u6210<\/strong><\/h4>\n<p>\u591a\u66ff\u62c9\u97e6\u662f\u7531\u845b\u5170\u7d20\u53f2\u514b\u516c\u53f8\u5f00\u53d1\u7684\u7528\u4e8e\u6cbb\u7597\u827e\u6ecb\u75c5\u7684\u9996\u9009\u4e00\u7ebf\u548c\u4e8c\u7ebf\u836f\u7269\uff0c\u5305\u62ec\u5b55\u5987\u548c\u6709\u751f\u80b2\u80fd\u529b\u7684\u5987\u5973\u3002\u4ece\u5316\u5b66\u89d2\u5ea6\u6765\u770b\uff0c\u5b83\u662f\u4e00\u7c7b\u9ad8\u5ea6\u5b98\u80fd\u56e2\u5316\u7684\u5421\u5576\u916e\uff08pyridone\uff09\u7ed3\u6784\u884d\u751f\u7269\uff0c\u5982\u4f55\u9ad8\u6548\u5408\u6210\u8fd9\u7c7b\u6bcd\u6838\u7ed3\u6784\u65e0\u7591\u4e3a\u540e\u7eed\u76f8\u5173\u836f\u7269\u7814\u53d1\u63d0\u4f9b\u91cd\u8981\u53c2\u8003\u30022018\u5e74\uff0cT. D. Roper\u548cT. F. Jamison\u7b49\u4eba\u62a5\u9053\u4e86\u5229\u7528\u6d41\u52a8\u5316\u5b66\uff08Flow Chemistry\uff09\u7684\u65b9\u6cd57\u6b65\u5408\u6210\u4e86\u591a\u66ff\u62c9\u97e6\uff0c\u603b\u4ea7\u738724%\uff0c\u6d41\u52a8\u5316\u5b66\u63d0\u4f9b\u4e86\u4e00\u79cd\u65b0\u9896\u7684\u5408\u6210\u7b56\u7565\u3002<sup>[5]<\/sup><\/p>\n<p>2019\u5e74\uff0c\u65e5\u672c\u79d1\u5b66\u5bb6T. Yasukata\u7b49\u4eba\u62a5\u9053\u4e86\u53e6\u4e00\u79cd\u7b80\u5355\u7684\u5408\u6210\u65b9\u6cd5\u3002\u4ed6\u4eec\u4ee5\u7b80\u5355\u7684\u9ea6\u82bd\u915a\uff08maltol\uff09\u4e3a\u8d77\u59cb\u539f\u6599\uff0c\u7ecf\u4eb2\u6838\u53d6\u4ee3\u3001\u6d88\u53bb\u3001\u6c27\u5316\u3001\u916f\u5316\u7b49\u8fd1\u5341\u6b65\u53cd\u5e94\u5408\u6210\u4e86\u590d\u6742\u7684\u5421\u5576\u916e\u6bcd\u6838\u4e2d\u95f4\u4f53<strong>A<\/strong>\uff0c\u968f\u540e\u7ecf\u201c\u63d2\u7fb0\u5076\u8054\u201d\u6210\u529f\u5c06\u6c1f\u4ee3\u82c4\u80fa\u5f15\u5165\u6bcd\u6838\uff0c\u50ac\u5316\u52a0\u6c22\u8131\u82c4\u57fa\u4fdd\u62a4\u5373\u53ef\u83b7\u5f97\u6700\u7ec8\u4ea7\u7269\u3002\u5c3d\u7ba1\u8def\u7ebf\u7a0d\u663e\u5197\u957f\uff0c\u4f46\u7531\u4e8e\u6bcf\u6b65\u7684\u4ea7\u7387\u90fd\u5f88\u7406\u60f3\u4e14\u539f\u6599\u5ec9\u4ef7\u6613\u5f97\uff0c\u66f4\u9002\u7528\u4e8e\u5927\u89c4\u6a21\u751f\u4ea7\uff0c\u56e0\u6b64\u4e5f\u4e0d\u77e2\u4e3a\u4e00\u79cd\u4f18\u79c0\u7684\u5408\u6210\u8def\u7ebf\u3002<sup>[6]<\/sup><\/p>\n<p><a href=\"https:\/\/assets.www.gsbet888.com\/uploads\/2019\/11\/4-4.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter wp-image-29378 \" src=\"https:\/\/assets.www.gsbet888.com\/uploads\/2019\/11\/4-4.jpg\" alt=\"\" width=\"829\" height=\"461\" srcset=\"https:\/\/assets.www.gsbet888.com\/uploads\/2019\/11\/4-4.jpg 1212w, https:\/\/assets.www.gsbet888.com\/uploads\/2019\/11\/4-4-300x167.jpg 300w, https:\/\/assets.www.gsbet888.com\/uploads\/2019\/11\/4-4-768x426.jpg 768w, https:\/\/assets.www.gsbet888.com\/uploads\/2019\/11\/4-4-680x378.jpg 680w\" sizes=\"(max-width: 829px) 100vw, 829px\" \/><\/a><\/p>\n<p style=\"text-align: center;\">\u56fe 4 \u591a\u66ff\u62c9\u97e6\u7684\u4ee3\u8868\u6027\u5408\u6210\u8def\u7ebf<\/p>\n<h4><strong>\u4e94\u3001\u7ed3\u675f\u8bed<\/strong><\/h4>\n<p>\u73b0\u5982\u4eca\uff0c\u968f\u7740\u73b0\u4ee3\u533b\u5b66\u6280\u672f\u7684\u4e0d\u65ad\u7a81\u98de\u731b\u8fdb\uff0c\u8d8a\u6765\u8d8a\u591a\u7684\u75be\u75c5\u88ab\u4eba\u7c7b\u514b\u670d\u3002\u8fd9\u4e00\u8fc7\u7a0b\u4e2d\uff0c\u4eba\u4eec\u5bf9\u827e\u6ecb\u75c5\u6bd2\u7684\u81f4\u75c5\u673a\u5236\u3001\u4f20\u64ad\u65b9\u5f0f\u3001\u9884\u9632\u3001\u8bca\u65ad\u4ee5\u53ca\u6cbb\u7597\u7b49\u90fd\u6709\u4e86\u66f4\u52a0\u6e05\u695a\u7684\u8ba4\u8bc6\uff0c\u4e5f\u6709\u8d8a\u6765\u8d8a\u591a\u7684\u836f\u7269\u6295\u5165\u4e34\u5e8a\u4f7f\u7528\uff0c\u5728\u4eba\u7c7b\u4e0e\u75c5\u6bd2\u7684\u4e0d\u61c8\u6597\u4e89\u4e2d\u53d1\u6325\u4e86\u5de8\u5927\u4f5c\u7528\u3002\u7136\u800c\uff0c\u6211\u4eec\u8fd8\u662f\u8981\u6e05\u695a\u5730\u610f\u8bc6\u5230\uff0c\u76ee\u524d\u5168\u7403\u8303\u56f4\u5185\u201c\u6297\u827e\u201d\u5f62\u52bf\u90fd\u5341\u5206\u4e25\u5cfb\uff0c\u591a\u66ff\u62c9\u97e6\u8fd9\u6837\u7684\u836f\u7269\u8fd8\u8fdc\u4e0d\u80fd\u6cbb\u6108\u827e\u6ecb\u75c5\uff0c\u66f4\u4e0d\u80fd\u8ba9\u6211\u4eec\u8fc7\u4e8e\u4e50\u89c2\u3002\u6211\u4eec\u5e94\u5f53\u575a\u4fe1\uff0c\u968f\u7740\u79d1\u5b66\u6280\u672f\u7684\u4e0d\u65ad\u65e5\u65b0\u6708\u5f02\uff0c\u7ec8\u6709\u4e00\u65e5\u4eba\u7c7b\u4f1a\u5728\u8fd9\u573a\u6f2b\u957f\u6218\u6597\u4e2d\u53d6\u5f97\u80dc\u5229\uff01<\/p>\n<h4>\u53c2\u8003\u8d44\u6599<\/h4>\n<ul style=\"list-style-type: disc;\">\n<li>[1] <a href=\"https:\/\/www.who.int\/zh\/news-room\/fact-sheets\/detail\/hiv-aids\">\u91cd\u8981\u4e8b\u5b9e<\/a>. \u4e16\u754c\u536b\u751f\u7ec4\u7ec7.<\/li>\n<li>[2] \u7ef4\u57fa\u767e\u79d1\uff1a<a href=\"https:\/\/en.wikipedia.org\/wiki\/HIV\">https:\/\/en.wikipedia.org\/wiki\/HIV<\/a><\/li>\n<li>[3] \u7f57\u4e3d\u5a1f, \u9ec4\u7490, and \u5f20\u7389\u82b9. &#8220;HIV \u6574\u5408\u9176\u6291\u5236\u5242\u836f\u7269\u7814\u7a76\u4e0e\u5e94\u7528.&#8221; \u4e2d\u56fd\u65b0\u836f\u4e0e\u4e34\u5e8a\u6742\u5fd7 2014, 33, 481-484.<\/li>\n<li>[4] \u8054\u5408\u56fd\u65b0\u95fb\uff1a<a href=\"https:\/\/news.un.org\/zh\/story\/2019\/07\/1038571\">https:\/\/news.un.org\/zh\/story\/2019\/07\/1038571<\/a><\/li>\n<li>[5] T. D. Roper, and T. F. Jamison. et al. &#8220;7\u2010Step Flow Synthesis of the HIV Integrase Inhibitor Dolutegravir.&#8221; <em>Angew. Chem. Int. Ed.<\/em> <strong>2018<\/strong>, <em>57<\/em>, 7181-7185. DOI: <a href=\"https:\/\/onlinelibrary.wiley.com\/doi\/full\/10.1002\/anie.201802256\">10.1002\/anie.201802256<\/a><\/li>\n<li>[6] Y. Tatsuro, et al. &#8220;Practical Synthetic Method for the Preparation of Pyrone Diesters: An Efficient Synthetic Route for the Synthesis of Dolutegravir Sodium.&#8221; <em>Org. Process Res. Dev.<\/em> <strong>2019<\/strong>, <em>23<\/em>, 565-570. DOI: <a href=\"https:\/\/pubs.acs.org\/doi\/abs\/10.1021\/acs.oprd.8b00410\">10.1021\/acs.oprd.8b00410<\/a><\/li>\n<\/ul>\n<p><strong>\u672c\u6587\u7248\u6743\u5c5e\u4e8e\u00a0<\/strong><a href=\"\/\/www.gsbet888.com\/\"><strong>Chem-Station\u5316\u5b66\u7a7a\u95f4<\/strong><\/a><strong>\uff0c \u6b22\u8fce\u70b9\u51fb\u6309\u94ae\u5206\u4eab\uff0c\u672a\u7ecf\u8bb8\u53ef\uff0c\u8c22\u7edd\u8f6c\u8f7d\uff01<\/strong><\/p>\n","protected":false},"excerpt":{"rendered":"\u4e00\u3001\u5f15\u8a00 \u827e\u6ecb\u75c5\u662f\u83b7\u5f97\u6027\u514d\u75ab\u7f3a\u9677\u7efc\u5408\u5f81\uff08Acquired Immune Deficiency Syndrome\uff0cAIDS\uff09\u7684\u97f3\u8bd1\uff0c\u5b83\u6e90\u4e8e\u4e00\u79cd\u540d\u4e3a\u4eba\u7c7b\u514d\u75ab\u7f3a\u9677\u75c5\u6bd2\uff08Human Immunodeficiency Virus\uff0cHIV\uff09\u7684\u9006\u8f6c\u5f55\u75c5\u6bd2\uff0c\u611f\u67d3\u540e\u7834\u574f\u4eba\u4f53\u514d\u75ab\u7cfb\u7edf\uff0c\u4f7f\u5f97\u4eba\u4f53\u6781\u6613\u611f\u67d3\u591a\u79cd\u75be\u75c5\u6216\u56e0\u5404\u79cd\u5e76\u53d1\u75c7\u800c\u6b7b\u4ea1\u3002\u6839\u636e\u4e16\u536b\u7ec4\u7ec7\u548c\u8054\u5408\u56fd\u827e\u6ecb\u75c5\u89c4\u5212\u7f72\u7684\u4f30\u8ba1\uff0c\u622a\u81f32018\u5e74\u5e95\uff0c\u5168\u7403\u7ea6\u67093790\u4e07\u827e\u6ecb\u75c5\u6bd2\u611f\u67d3\u8005\uff0c\u5e76\u4e14\u8fd9\u4e2a\u6570\u5b57\u6bcf\u5e74\u90fd\u5728\u589e\u52a0[1]\uff0c\u66f4\u4e3a\u4e25\u5cfb\u7684\u662f\u76ee\u524d\u827e\u6ecb\u75c5\u6bd2\u611f\u67d3\u4e0d\u53ef\u6cbb\u6108\uff0c\u4ec5\u80fd\u901a\u8fc7\u957f\u671f\u670d\u7528\u836f\u7269\u5c06\u4f53\u5185\u75c5\u6bd2\u6291\u5236\u4e8e\u8f83\u4f4e\u6c34\u5e73\u3002 \u56fe 1 2017\u5e74\u5168\u740315-49\u5c81\u6210\u5e74\u4eba\u4e2d\u827e\u6ecb\u75c5\u6bd2\u7684\u6d41\u884c\u7387\uff08\u56fe\u7247\u6765\u6e90\u4e8eWHO\uff09 \u4e8c\u3001\u827e\u6ecb\u75c5\u6bd2\u7684\u590d\u5236 \u827e\u6ecb\u75c5\u6bd2\u611f\u67d3\u5bbf\u4e3b\u7ec6\u80de\u540e\u9700\u8981\u590d\u5236\u4ea7\u751f\u66f4\u591a\u7684\u540e\u4ee3\uff0c\u590d\u5236\u8fc7\u7a0b\u6d89\u53ca\u591a\u4e2a\u91cd\u8981\u73af\u8282\uff0c\u7406\u8bba\u4e0a\u800c\u8a00\u4e2d\u65ad\u4efb\u4f55\u8fc7\u7a0bHIV\u75c5\u6bd2\u90fd\u4e0d\u80fd\u6210\u529f\u590d\u5236\uff0c\u56e0\u800c\u8fd9\u4e9b\u5173\u952e\u73af\u8282\u4e5f\u6210\u4e86\u7814\u5236\u827e\u6ecb\u836f\u7269\u7684\u91cd\u8981\u9776\u70b9\u3002\u6b64\u5904\uff0c\u6211\u4eec\u4ec5\u5bf9\u827e\u6ecb\u75c5\u6bd2\u5b8c\u6574\u7684\u590d\u5236\u5468\u671f\u8fdb\u884c\u7b80\u8981\u4ecb\u7ecd\u3002 \u9996\u5148\uff0cHIV\u75c5\u6bd2\u548cCD4\u7ec6\u80de\u76f8\u4e92\u8bc6\u522b\u878d\u5408\u540e\u5c06\u81ea\u5df1\u7684RNA\u6ce8\u5165\u5bbf\u4e3b\u7ec6\u80de\uff0c\u968f\u540e\u75c5\u6bd2RNA\u5728\u9006\u8f6c\u5f55\u9176\u7684\u4f5c\u7528\u4e0b\u9006\u8f6c\u5f55\uff08Reverse Transcription\uff09\u6210DNA\uff0c\u7ecf\u9006\u8f6c\u5f55\u800c\u6765\u7684\u75c5\u6bd2DNA\u53ef\u4ee5\u987a\u5229\u8fdb\u5165\u5bbf\u4e3b\u7ec6\u80de\u7684\u7ec6\u80de\u6838\uff0c\u8fd8\u80fd\u5728\u6574\u5408\u9176\uff08Integrase\uff09\u7684\u4f5c\u7528\u4e0b\uff0c\u201c\u5802\u800c\u7687\u4e4b\u201d\u5c06\u81ea\u5df1\u6574\u5408\u5230\u5bbf\u4e3b\u7ec6\u80de\u7684DNA\u5f53\u4e2d\uff0c\u6210\u4e3a\u5bbf\u4e3b\u7ec6\u80de\u7684\u4e00\u90e8\u5206\u3002HIV\u75c5\u6bd2\u7684\u9057\u4f20\u7269\u8d28\u5c31\u8fd9\u6837\u6210\u529f\u4f2a\u88c5\u8fdb\u5bbf\u4e3b\u7ec6\u80de\u57fa\u56e0\u7ec4\uff0c\u63a5\u7740\u5c31\u53ef\u4ee5\u987a\u7406\u6210\u7ae0\u5730\u5229\u7528\u5bbf\u4e3b\u7ec6\u80de\u7684\u8f6c\u5f55\u673a\u5236\uff0c\u6765\u8f6c\u5f55\u5404\u79cd\u75c5\u6bd2RNA\uff0c\u4ee5\u53ca\u5408\u6210\u5404\u79cd\u75c5\u6bd2\u86cb\u767d\uff0c\u5408\u6210\u597d\u7684\u75c5\u6bd2RNA\u548c\u75c5\u6bd2\u86cb\u767d\u8fd8\u8981\u5728\u5bbf\u4e3b\u7ec6\u80de\u5185\u7ec4\u88c5\u6210\u719f\uff0c\u5f62\u6210\u540e\u4ee3\u75c5\u6bd2\u9897\u7c92\u7684\u96cf\u5f62\uff0c\u518d\u7ecf\u86cb\u767d\u9176\u7684\u4fee\u9970\u4f5c\u7528\uff0c\u6700\u7ec8\u6210\u4e3a\u6709\u611f\u67d3\u80fd\u529b\u7684\u5b8c\u6574\u7684HIV\u75c5\u6bd2\u9897\u7c92\u3002[2] \u56fe 2 \u827e\u6ecb\u75c5\u6bd2\u7684\u590d\u5236\u5468\u671f\u793a\u610f\u56fe \u4e09\u3001\u6cbb\u7597\u827e\u6ecb\u75c5\u7684\u5e38\u89c1\u836f\u7269 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[2] \u7ef4\u57fa\u767e\u79d1\uff1ahttps:\/\/en.wikipedia.org\/wiki\/HIV [3] \u7f57\u4e3d\u5a1f, \u9ec4\u7490, and \u5f20\u7389\u82b9. &#8220;HIV \u6574\u5408\u9176\u6291\u5236\u5242\u836f\u7269\u7814\u7a76\u4e0e\u5e94\u7528.&#8221; \u4e2d\u56fd\u65b0\u836f\u4e0e\u4e34\u5e8a\u6742\u5fd7 2014, 33, 481-484. [4] \u8054\u5408\u56fd\u65b0\u95fb\uff1ahttps:\/\/news.un.org\/zh\/story\/2019\/07\/1038571 [5] T. D. Roper, and T. F. Jamison. et al. &#8220;7\u2010Step Flow Synthesis of the HIV Integrase Inhibitor Dolutegravir.&#8221; Angew. Chem. Int. Ed. 2018, 57, 7181-7185. DOI: 10.1002\/anie.201802256 [6] Y. Tatsuro, et al. &#8220;Practical Synthetic Method for the Preparation of Pyrone Diesters: An Efficient Synthetic Route for the Synthesis of Dolutegravir Sodium.&#8221; Org. 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