作为双三氟乙酸盐的HIV-1进入抑制剂BNM-III-170的有效可扩展对映选择性合成方法的开发。
Development of an Effective Scalable Enantioselective Synthesis of the HIV-1 Entry Inhibitor BNM-III-170 as the Bis-Trifluoroacetate Salt.
作者信息
Chen Junhua, Park Jun, Kirk Sharon M, Chen Hung-Ching, Li Xiangqin, Lippincott Daniel J, Melillo Bruno, Smith Amos B
机构信息
Department of Chemistry, Monell Chemical Senses Center and Laboratory for Research on the Structure of Matter, University of Pennsylvania, Philadelphia, PA 19104.
出版信息
Org Process Res Dev. 2019 Nov 15;23(11):2464-2469. doi: 10.1021/acs.oprd.9b00353. Epub 2019 Oct 7.
Abstract
We report here the development and optimization of a process synthesis for the HIV-1 entry inhibitor BNM-III-170 bis-TFA salt (). The synthesis features a dynamic-kinetic resolution (DKR) to establish the initial stereogenicity. By taking advantage of significant sequence modifications of our first generation synthesis, inconjunction with the low solubility of late-stage intermediates, the overall efficiency of the synthesis has been significantly improved, now to proceed in an overall yield of 9.64% for the 16-steps, requiring only a single chromatographic separation.
摘要
我们在此报告了HIV-1进入抑制剂BNM-III-170双三氟乙酸盐（）的工艺合成的开发与优化。该合成的特点是采用动态动力学拆分（DKR）来建立初始立体化学。通过利用我们第一代合成中显著的序列修饰，并结合后期中间体的低溶解度，合成的整体效率得到了显著提高，现在16步反应的总收率为9.64%，仅需一次色谱分离。
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Development of an Effective Scalable Enantioselective Synthesis of the HIV-1 Entry Inhibitor BNM-III-170 as the Bis-Trifluoroacetate Salt.作为双三氟乙酸盐的HIV-1进入抑制剂BNM-III-170的有效可扩展对映选择性合成方法的开发。
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