Development of an Effective Scalable Enantioselective Synthesis of the HIV-1 Entry Inhibitor BNM-III-170 as the Bis-trifluoroacetate Salt

被引：17

作者：

Chen, Junhua ^{[1
,2
]}

Park, Jun ^{[1
,2
]}

Kirk, Sharon M. ^{[1
,2
]}

Chen, Hung-Ching ^{[1
,2
]}

Li, Xiangqin ^{[1
,2
]}

Lippincott, Daniel J. ^{[1
,2
]}

Melillo, Bruno ^{[1
,2
]}

Smith, Amos B., III ^{[1
,2
]}

机构：

[1] Univ Penn, Dept Chem, Monell Chem Senses Ctr, Philadelphia, PA 19104 USA

[2] Univ Penn, Res Struct Matter Lab, Philadelphia, PA 19104 USA

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2019年 / 23卷 / 11期

基金：

美国国家卫生研究院;

关键词：

CD4-mimetic; HIV-1 entry inhibitor; dynamic-kinetic resolution; guanidine formation; aminolysis; Gabriel amine synthesis; OPTIMIZATION; CONVERSION; DESIGN;

D O I：

10.1021/acs.oprd.9b00353

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

We report here the development and optimization of a process synthesis for the human immunodeficiency virus-1 entry inhibitor BNM-III-170 bis-trifluoroacetate salt (1). The synthesis features a dynamic-kinetic resolution to establish the initial stereogenicity. By taking advantage of significant sequence modifications of our first-generation synthesis, in conjunction 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.

引用

页码：2464 / 2469

页数：6

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