Synthesis of 1,4-imino-L-lyxitols modified at C-5 and their evaluation as inhibitors of GH38 α-mannosidases

• Maroš Bella,
• Sergej Šesták,
• Ján Moncoľ,
• Miroslav Koóš and
• Monika Poláková

Beilstein J. Org. Chem. 2018, 14, 2156–2162, doi:10.3762/bjoc.14.189

• ; inhibitors; pyrrolidines; synthesis; Introduction Carbohydrates as chiral templates for a construction of bioactive compounds are of steady interest in medicinal chemistry [1][2][3]. The polyfunctional nature of carbohydrate units offers many possibilities for the design of a wide variety of new compounds

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• , 4070 Basel, Switzerland 10.3762/bjoc.14.179 Abstract The focus of this review is to provide an overview of the field of organocatalysed photoredox chemistry relevant to synthetic medicinal chemistry. Photoredox transformations have been shown to enable key transformations that are important to the

• value of these methods to medicinal chemistry is considered. An overview of the general characteristics of the photocatalysts as well as some electrochemical data is presented. In addition, the general reaction mechanisms for organocatalysed photoredox transformations are discussed and some individual

• mechanistic considerations are highlighted in the text when appropriate. Keywords: C–H functionalisation; heterocycles; late-stage functionalisation; medicinal chemistry; organic dyes; organic photocatalysts; peptide chemistry; photoredox catalysis; Review 1 Introduction 1.1 Main advantages of

Diazirine-functionalized mannosides for photoaffinity labeling: trouble with FimH

• Femke Beiroth,
• Tomas Koudelka,
• Thorsten Overath,
• Stefan D. Knight,
• Andreas Tholey and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1890–1900, doi:10.3762/bjoc.14.163

• ) of bacteria to the glycosylated surface of their target cells and constitute important virulence factors in bacterial infection such as urinary tract infection [13][14][15][16]. Hence, FimH is an interesting target protein in medicinal chemistry and proteomics [17][18]. It is a two-domain protein

Synthesis of spirocyclic scaffolds using hypervalent iodine reagents

• Fateh V. Singh,
• Priyanka B. Kole,
• Saeesh R. Mangaonkar and
• Samata E. Shetgaonkar

Beilstein J. Org. Chem. 2018, 14, 1778–1805, doi:10.3762/bjoc.14.152

• established research area of organic and medicinal chemistry [1][2][3][4][5]. These scaffolds are common structural motifs found in various classes of naturally occurring systems [6][7][8]. More importantly, various natural and synthetic products containing a spirocyclic ring are currently used as commercial

DFT calculations on the mechanism of copper-catalysed tandem arylation–cyclisation reactions of alkynes and diaryliodonium salts

• Tamás Károly Stenczel,
• Ádám Sinai,
• Zoltán Novák and
• András Stirling

Beilstein J. Org. Chem. 2018, 14, 1743–1749, doi:10.3762/bjoc.14.148

• , Hungary Servier Research Institute of Medicinal Chemistry, Záhony utca 7, H-1031, Budapest, Hungary Research Centre for Natural Sciences of the Hungarian Academy of Sciences, Institute of Organic Chemistry, Budapest, Hungary 10.3762/bjoc.14.148 Abstract We present a computational mechanistic study on the

Synthesis of pyrimido[1,6-a]quinoxalines via intermolecular trapping of thermally generated acyl(quinoxalin-2-yl)ketenes by Schiff bases

• Svetlana O. Kasatkina,
• Ekaterina E. Stepanova,
• Maksim V. Dmitriev,
• Ivan G. Mokrushin and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2018, 14, 1734–1742, doi:10.3762/bjoc.14.147

• ; Introduction Quinoxaline is a 4-aza isostere of quinoline, which rarely occurs in structures of natural products. Its derivatives are gaining popularity in medicinal chemistry and pharmacology because many of them exhibit various biological activities [1][2]. Quinoxaline-based 6/6/6-angularly fused scaffolds

Visible light-mediated difluoroalkylation of electron-deficient alkenes

• Vyacheslav I. Supranovich,
• Vitalij V. Levin,
• Marina I. Struchkova,
• Jinbo Hu and
• Alexander D. Dilman

Beilstein J. Org. Chem. 2018, 14, 1637–1641, doi:10.3762/bjoc.14.139

• organofluorine compounds in medicinal chemistry and related fields [1][2] have stimulated intensive developments of methods for their synthesis [3][4]. Though the major emphasis has long been placed on trifluoromethylated molecules, compounds bearing the difluoromethylene fragment have attracted increasing

Synthesis of trifluoromethylated 2H-azirines through Togni reagent-mediated trifluoromethylation followed by PhIO-mediated azirination

• Jiyun Sun,
• Xiaohua Zhen,
• Huaibin Ge,
• Guangtao Zhang,
• Xuechan An and
• Yunfei Du

Beilstein J. Org. Chem. 2018, 14, 1452–1458, doi:10.3762/bjoc.14.123

• -dimethyl-1,2-benziodoxole (1’, Figure 2), are effective and efficient hypervalent iodine reagents for trifluoromethylation reactions of a variety of substrates [22][23]. These reagents have found wide applications in the area of organofluorine chemistry, synthetic method development as well as medicinal

• chemistry [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40]. For example, the Togni reagents have been successfully applied to introduce the CF3 group into pharmaceutical agents such as the fluoxetine derivative D (Figure 1), the mefloquine derivative E [41] and compound F [42] – a

Three-component coupling of aryl iodides, allenes, and aldehydes catalyzed by a Co/Cr-hybrid catalyst

• Kimihiro Komeyama,
• Shunsuke Sakiyama,
• Kento Iwashita,
• Itaru Osaka and
• Ken Takaki

Beilstein J. Org. Chem. 2018, 14, 1413–1420, doi:10.3762/bjoc.14.118

• ; Introduction Carbon–carbon bond formation is the fundamental and central transformation of synthetic organic chemistry. The elaboration and extension of a carbon framework via a series of carbon–carbon bond-forming reactions are extremely important for medicinal chemistry and agrochemical and natural product

Synthesis of chiral 3-substituted 3-amino-2-oxindoles through enantioselective catalytic nucleophilic additions to isatin imines

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 1349–1369, doi:10.3762/bjoc.14.114

• them, chiral 3-substituted 3-amino-2-oxindoles constitute privileged candidates in medicinal chemistry [1][2][3][4][5][6][7][8]. Consequently, the development of novel catalytic routes to produce these compounds is highly desired [9][10][11][12][13][14][15][16][17][18][19] with a special mention for

Oligonucleotide analogues with cationic backbone linkages

• Melissa Meng and
• Christian Ducho

Beilstein J. Org. Chem. 2018, 14, 1293–1308, doi:10.3762/bjoc.14.111

• Melissa Meng Christian Ducho Department of Pharmacy, Pharmaceutical and Medicinal Chemistry, Saarland University, Campus C2 3, 66123 Saarbrücken, Germany 10.3762/bjoc.14.111 Abstract Their unique ability to selectively bind specific nucleic acid sequences makes oligonucleotides promising

A survey of chiral hypervalent iodine reagents in asymmetric synthesis

• Soumen Ghosh,
• Suman Pradhan and
• Indranil Chatterjee

Beilstein J. Org. Chem. 2018, 14, 1244–1262, doi:10.3762/bjoc.14.107

• challenging and application-oriented conversions that can be applied for the total synthesis of natural products as well as in industry related to pharmaceutical and medicinal chemistry. These environmentally friendly, cheap and readily available reagents will surely attract the attention of scientists

Rhodium-catalyzed C–H functionalization of heteroarenes using indoleBX hypervalent iodine reagents

• Erwann Grenet,
• Ashis Das,
• Paola Caramenti and
• Jérôme Waser

Beilstein J. Org. Chem. 2018, 14, 1208–1214, doi:10.3762/bjoc.14.102

• Nitrogen-containing heteroaromatic compounds have valuable properties in medicinal chemistry, pharmacology and functional materials. Among those, pyridinone, sometimes called pyridone, is a key structural motif of well-known active compounds and natural products (Figure 1) [1]. For example, the 2

• C-8 position of quinoline N-oxides, whereas formation of the quinolinone had been observed in our previous work (Scheme 1B). The obtained products combine up to three classes of privileged heterocycles in medicinal chemistry in a single compound, and are therefore expected to be highly useful

• -oxide function, we were able to access 6-(indol-3-yl)pyridinone and 8-(indol-3-yl)quinolone. The developed transformations give access to important heterocyclic building blocks for synthetic and medicinal chemistry and set the stages for the development of other C–H heteroarylation processes based on

Hypervalent iodine-mediated Ritter-type amidation of terminal alkenes: The synthesis of isoxazoline and pyrazoline cores

• Sang Won Park,
• Soong-Hyun Kim,
• Jaeyoung Song,
• Ga Young Park,
• Darong Kim,
• Tae-Gyu Nam and
• Ki Bum Hong

Beilstein J. Org. Chem. 2018, 14, 1028–1033, doi:10.3762/bjoc.14.89

• of pharmaceutical and medicinal chemistry [6][7][8][9][10][11]. Not surprisingly, the construction of diverse heterocyclic cores including isoxazolines and pyrazolines has garnered much attention from synthetic chemists [12][13][14][15]. Among precedent synthetic methods, the functionalization of

The first Pd-catalyzed Buchwald–Hartwig aminations at C-2 or C-4 in the estrone series

• Ildikó Bacsa,
• Dávid Szemerédi,
• János Wölfling,
• Gyula Schneider,
• Lilla Fekete and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 998–1003, doi:10.3762/bjoc.14.85

• Ildiko Bacsa David Szemeredi Janos Wolfling Gyula Schneider Lilla Fekete Erzsebet Mernyak Department of Organic Chemistry, University of Szeged, Dóm tér 8, H-6720 Szeged, Hungary Department of Medicinal Chemistry, University of Szeged, Dóm tér 8, H-6720 Szeged, Hungary 10.3762/bjoc.14.85 Abstract

An efficient and facile access to highly functionalized pyrrole derivatives

• Meng Gao,
• Wenting Zhao,
• Hongyi Zhao,
• Ziyun Lin,
• Dongfeng Zhang and
• Haihong Huang

Beilstein J. Org. Chem. 2018, 14, 884–890, doi:10.3762/bjoc.14.75

• substrates. It is conceivable that this efficient construction method for privileged pyrrole scaffolds could deliver more active compounds for medicinal chemistry research. Keywords: azomethine ylides; 1,3-dipolar cycloaddition; one-pot synthesis; polysubstituted pyrroles; pyrrolo[3,4-c]pyrrole-1,3-diones

• in medicinal chemistry (Figure 1), such as analgesic agent 1 [1], BET bromodomain inhibitor 2 [2], selective PARP-1 inhibitor 3 [3], histone deacetylase inhibitor with antitumor activity 4 [4], Flavivirus inhibitor 5 [5], and for treating cardiovascular diseases (atorvastatin, 6) [6]. A number of

Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

• Kartik Temburnikar and
• Katherine L. Seley-Radtke

Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65

Syn-selective silicon Mukaiyama-type aldol reactions of (pentafluoro-λ⁶-sulfanyl)acetic acid esters with aldehydes

• Anna-Lena Dreier,
• Andrej V. Matsnev,
• Joseph S. Thrasher and
• Günter Haufe

Beilstein J. Org. Chem. 2018, 14, 373–380, doi:10.3762/bjoc.14.25

• years, the pentafluoro-λ6-sulfanyl (SF5) substituent has come into the focus of chemists because of the remarkable effects of this substituent on the physical and chemical properties of compounds, which are important for agricultural and medicinal chemistry as well as for materials sciences. While

One-pot sequential synthesis of tetrasubstituted thiophenes via sulfur ylide-like intermediates

• Jun Ki Kim,
• Hwan Jung Lim,
• Kyung Chae Jeong and
• Seong Jun Park

Beilstein J. Org. Chem. 2018, 14, 243–252, doi:10.3762/bjoc.14.16

• Jun Ki Kim Hwan Jung Lim Kyung Chae Jeong Seong Jun Park Research Center for Medicinal Chemistry, Korea Research Institute of Chemical Technology (KRICT), 141 Gajeong-ro, Yuseong-gu, Daejeon 34114, Korea Department of Chemistry, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134

Progress in copper-catalyzed trifluoromethylation

• Guan-bao Li,
• Chao Zhang,
• Chun Song and
• Yu-dao Ma

Beilstein J. Org. Chem. 2018, 14, 155–181, doi:10.3762/bjoc.14.11

• functional group and copper(I). Benzamides were widely used building blocks in medicinal chemistry. In 2014, Dai and Yu [54] achieved an elegant copper-mediated ortho-selective trifluoromethylation of benzamides assisted by an N-phenyloxazoline group. But one major problem was the low selectivity, and that

The photodecarboxylative addition of carboxylates to phthalimides as a key-step in the synthesis of biologically active 3-arylmethylene-2,3-dihydro-1H-isoindolin-1-ones

• Ommid Anamimoghadam,
• Saira Mumtaz,
• Anke Nietsch,
• Gaetano Saya,
• Cherie A. Motti,
• Jun Wang,
• Peter C. Junk,
• Ashfaq Mahmood Qureshi and
• Michael Oelgemöller

Beilstein J. Org. Chem. 2017, 13, 2833–2841, doi:10.3762/bjoc.13.275

• ; arylmethylenedihydroisoindolinones; photochemistry; photodecarboxylation; phthalimide; Introduction Phthalimides and their related 3-alkyl- and 3-arylmethylene-2,3-dihydro-1H-isoindolin-1-ones play an important role in medicinal chemistry due to their biological activities for a wide range of therapeutic applications [1][2][3][4

Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• of the geometry of the fluoroalkene (i.e., Z vs E) was important. Finally, as the monofluoroalkene is of interest in medicinal chemistry as a non-hydrolyzable peptide bond isostere, some applications have been presented. Selected amide bond isosteres. Monofluoroalkene as an amide bond isostere

Palladium-catalyzed Heck-type reaction of secondary trifluoromethylated alkyl bromides

• Tao Fan,
• Wei-Dong Meng and
• Xingang Zhang

Beilstein J. Org. Chem. 2017, 13, 2610–2616, doi:10.3762/bjoc.13.258

• past decade, investigations mainly focused on direct fluorination or fluoroalkylation of aromatics [1][2][3][4][5]. Fluoroalkylated alkenes are a kind of important fluorinated structural motifs and have wide applications in medicinal chemistry and advanced functional materials [6][7][8][9]. However

A novel synthetic approach to hydroimidazo[1,5-b]pyridazines by the recyclization of itaconimides and HPLC–HRMS monitoring of the reaction pathway

• Dmitry Yu. Vandyshev,
• Khidmet S. Shikhaliev,
• Andrey Yu. Potapov,
• Michael Yu. Krysin,
• Fedor I. Zubkov and
• Lyudmila V. Sapronova

Beilstein J. Org. Chem. 2017, 13, 2561–2568, doi:10.3762/bjoc.13.252

• ], antitumor agents [9], and are stimulators of guanylate cyclase [10], whereas imidazo[1,5-c]pyrimidines demonstrate anti-infectious effects in the treatment of brucellosis [11], etc. However, the chemistry, medicinal chemistry and pharmacology of imidazo[1,5-b]pyridazines, with the imidazole ring connected

¹⁵N-Labelling and structure determination of adamantylated azolo-azines in solution

• Sergey L. Deev,
• Alexander S. Paramonov,
• Tatyana S. Shestakova,
• Igor A. Khalymbadzha,
• Oleg N. Chupakhin,
• Julia O. Subbotina,
• Oleg S. Eltsov,
• Pavel A. Slepukhin,
• Vladimir L. Rusinov,
• Alexander S. Arseniev and
• Zakhar O. Shenkarev

Beilstein J. Org. Chem. 2017, 13, 2535–2548, doi:10.3762/bjoc.13.250

• natural compounds is a widely used approach in medicinal chemistry [1]. The increased lipophilicity of adamantane-containing compounds compared with non-adamantylated derivatives [2] leads to considerably higher solubility of these compounds in blood plasma and their easier penetration through cell

• -azine core with a bridgehead nitrogen atom is found in many natural products [5][6] and biologically active synthetic compounds [7][8]. The purine-like scaffold of these nitrogen-containing heterocycles is frequently used in medicinal chemistry and drug design. For example, 6-nitro-1,2,4-triazolo[5,1-c