Organocatalytic, Enantioselective Synthesis of VNI: A Robust Therapeutic Development Platform for Chagas, a Neglected Tropical Disease

被引：34

作者：

Dobish, Mark C. ^{[1
,2
]}

Villalta, Fernando ^{[3
]}

Waterman, Michael R. ^{[4
]}

Lepesheva, Galina I. ^{[4
]}

Johnston, Jeffrey N. ^{[1
,2
]}

机构：

[1] Vanderbilt Univ, Dept Chem, Nashville, TN 37235 USA

[2] Vanderbilt Univ, Vanderbilt Inst Chem Biol, Nashville, TN 37235 USA

[3] Meharry Med Coll, Dept Microbiol & Immunol, Nashville, TN 37208 USA

[4] Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37232 USA

来源：

ORGANIC LETTERS | 2012年 / 14卷 / 24期

基金：

美国国家卫生研究院;

关键词：

CHIRAL PROTON CATALYSIS; ALPHA-AMIDO SULFONES; MANNICH REACTIONS; CYP51; NITRO; NITROALKANES; INHIBITION; ACTIVATION; REACTIVITY; ADDITIONS;

D O I：

10.1021/ol303092v

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

VNI is a potent inhibitor of CYP51 and was recently shown to achieve a parasitological cure of mice infected with T. cruzi in both acute and chronic stages of infection. T. cruzi is the causative parasite of Chagas disease, a neglected tropical disease. The first enantioselective chemical synthesis of VNI (at a materials cost of less than $0.10/mg) is described. Furthermore, the key enantioselective step is performed at the 10 g scale.

引用

页码：6322 / 6325

页数：4

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