Difluorination of Furonaphthoquinones

被引：12

作者：

Li, Jie ^{[1
]}

Xue, Yu ^{[2
]}

Fan, Zhoulong ^{[3
,4
,5
]}

Ding, Chunyong ^{[3
,5
]}

Zhang, Ao ^{[1
,3
,4
,5
]}

机构：

[1] ShanghaiTech Univ, Shanghai 201210, Peoples R China

[2] China Pharmaceut Univ, Dept Med Chem, Nanjing 210009, Jiangsu, Peoples R China

[3] Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China

[4] Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China

[5] Univ Chinese Acad Sci, Beijing 100049, Peoples R China

来源：

JOURNAL OF ORGANIC CHEMISTRY | 2017年 / 82卷 / 14期

基金：

中国国家自然科学基金;

关键词：

PRODUCT TANSHINONE IIA; DIFLUOROMETHYL KETONES; MEDICINAL CHEMISTRY; SALVIA-MILTIORRHIZA; CARBONYL-COMPOUNDS; ACID-CHLORIDES; PLASMEPSIN II; DERIVATIVES; INHIBITORS; FLUORINE;

D O I：

10.1021/acs.joc.7b01064

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

An unprecedented difluorination reaction was developed based on the furonaphthoquinone skeleton of natural products tanshinones and their analogues. By using Selectfluor as the fluorinating source and H2O as the hydroxyl source, a wide range of unique polycyclic alpha,alpha-difluoro beta,beta-dihydroxyl para-quinone products were achieved with yields up to 90%. The mechanistic studies revealed that the reaction might undergo tandem multiple electrophilic and nucleophilic substitutions, as well as cleavages of C-O and C-C bonds. This approach not only provides a new method to synthesis of alpha,alpha-difluoro ketones, but also affords a series of unique chemotypes for biological activity screening.

引用

收藏

页码：7388 / 7393

页数：6

相关论文

共 44 条

[1] Synthesis and vasodilative activity of tanshinone IIA derivatives [J].

Bi, Yue-Feng ;

Xu, Hai-Wei ;

Liu, Xiao-Qing ;

Zhang, Xiao-Juan ;

Wang, Zhen-Ji ;

Liu, Hong-Min .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (16) :4892-4894

[2] Tricomponent Catalytic α,α-Difluorination of Acid Chlorides [J].

Bloom, Steven ;

Scerba, Michael T. ;

Erb, Jeremy ;

Lectka, Thomas .

ORGANIC LETTERS, 2011, 13 (19) :5068-5071

[3] Me3SiCF2Br-Self-Assisted Domino Reaction: Catalytic Synthesis of α,α-Difluorocyclopentanones from Methylvinylketones [J].

Chang, Jian ;

Xu, Cong ;

Gao, Jie ;

Gao, Fengyun ;

Zhu, Dongsheng ;

Wang, Mang .

ORGANIC LETTERS, 2017, 19 (07) :1850-1853

[4] New paradigm of an old target: An update on structural biology and current progress in drug design towards plasmepsin II [J].

Dan, Nirnoy ;

Bhakat, Soumendranath .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2015, 95 :324-348

[5] Catalyst-Free sp3 C-H Acyloxylation: Regioselective Synthesis of 1-Acyloxy Derivatives of the Natural Product Tanshinone IIA [J].

Ding, Chunyong ;

Li, Jie ;

Jiao, Mingkun ;

Zhang, Ao .

JOURNAL OF NATURAL PRODUCTS, 2016, 79 (10) :2514-2520

[6] Biosynthesis, total syntheses, and antitumor activity of tanshinones and their analogs as potential therapeutic agents [J].

Dong, Yizhou ;

Morris-Natschke, Susan L. ;

Lee, Kuo-Hsiung .

NATURAL PRODUCT REPORTS, 2011, 28 (03) :529-542

[7] New organofluorine building blocks: inhibition of the malarial aspartic proteases plasmepsin II and IV by alicyclic α,α-difluoroketone hydrates [J].

Faeh, Christoph ;

Hardegger, Leo A. ;

Baitsch, Lukas ;

Schweizer, W. Bernd ;

Meyer, Solange ;

Bur, Daniel ;

Diederich, Francois .

ORGANIC & BIOMOLECULAR CHEMISTRY, 2009, 7 (19) :3947-3957

[8] Pd-Catalyzed α-Arylation of α,α-Difluoroketones with Aryl Bromides and Chlorides. A Route to Difluoromethylarenes [J].

Ge, Shaozhong ;

Chaladaj, Wojciech ;

Hartwig, John F. .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2014, 136 (11) :4149-4152

[9] FLUORO KETONE INHIBITORS OF HYDROLYTIC ENZYMES [J].

GELB, MH ;

SVAREN, JP ;

ABELES, RH .

BIOCHEMISTRY, 1985, 24 (08) :1813-1817

[10] A Chelating Nucleophile Plays a Starring Role: 1,8-Naphthyridine-Catalyzed Polycomponent α,α-Difluorination of Acid Chlorides [J].

Griswold, Andrew ;

Bloom, Steven ;

Lectka, Thomas .

JOURNAL OF ORGANIC CHEMISTRY, 2014, 79 (20) :9830-9834

← 1 2 3 4 5 →