Organophosphorus chemistry

• Paul R. Hanson

Beilstein J. Org. Chem. 2014, 10, 2087–2088, doi:10.3762/bjoc.10.217

• heights. This Thematic Series highlights and details some of the novel methods that are advancing the field of organophosphorus chemistry. The Thematic Series covers topics that range from new synthetic methods and phosphorus-based ligands in asymmetric catalysis to bisphosphonates as promising enzyme

• inhibitors. More specifically, the Thematic Series spans new methods in C–P bond formation, chiral phosphines in nucleophilic organocatalysis, chiral N-phosphinyl auxiliaries, cyclic phosphonamide reagents in the total synthesis of natural products, phosphinate-containing heterocycles, new routes to

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

The search for new amphiphiles: synthesis of a modular, high-throughput library

• George C. Feast,
• Thomas Lepitre,
• Xavier Mulet,
• Charlotte E. Conn,
• Oliver E. Hutt,
• G. Paul Savage and
• Calum J. Drummond

Beilstein J. Org. Chem. 2014, 10, 1578–1588, doi:10.3762/bjoc.10.163

• delivery. Many other fields have utilised the copper-catalysed azide–alkyne cycloaddition (CuAAC) ‘click’ reaction [16][17] to generate libraries of compounds, including enzyme inhibitors [18][19][20], catalysis ligands [21][22][23] and metal frameworks [24][25]. We have recently demonstrated that a

Carbohydrate PEGylation, an approach to improve pharmacological potency

• M. Eugenia Giorgi,
• Rosalía Agusti and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2014, 10, 1433–1444, doi:10.3762/bjoc.10.147

• PEGylation of carbohydrates show improvement of some properties such as bioavailability of drugs, in particular enzyme inhibitors, or creation of polymers with encapsulating properties for drugs. Apparently, the benefits of PEGylation were yet not extended to carbohydrate based drugs in the market. In

Asymmetric Ugi 3CR on isatin-derived ketimine: synthesis of chiral 3,3-disubstituted 3-aminooxindole derivatives

• Giordano Lesma,
• Fiorella Meneghetti,
• Alessandro Sacchetti,
• Mattia Stucchi and
• Alessandra Silvani

Beilstein J. Org. Chem. 2014, 10, 1383–1389, doi:10.3762/bjoc.10.141

• additions or spiroannulation [2][3]. Oxindoles represent a common structural element in various natural products and biologically active compounds. Diverse oxindole derivatives act as non-peptide scaffolds [4] in peptidomimetic chemistry, either as enzyme inhibitors or as ligands of G-protein-coupled

Deoxygenative gem-difluoroolefination of carbonyl compounds with (chlorodifluoromethyl)trimethylsilane and triphenylphosphine

• Fei Wang,
• Lingchun Li,
• Chuanfa Ni and
• Jinbo Hu

Beilstein J. Org. Chem. 2014, 10, 344–351, doi:10.3762/bjoc.10.32

• precursors for organic synthesis, but also act as bioisosteres for enzyme inhibitors. Among various methods for their preparation, the carbonyl olefination with difluoromethylene phosphonium ylide represents one of the most straightforward methods. Results: The combination of (chlorodifluoromethyl

• used in the design of potential enzyme inhibitors [4][5][6], since difluoromethylene functionality (CF2) is known to be isosteric and isopolar to an oxygen atom [7][8][9], and the gem-difluorovinyl functionality is believed to be a bioisostere for a carbonyl group [10]. More commonly, 1,1

Stereoselectively fluorinated N-heterocycles: a brief survey

• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2013, 9, 2696–2708, doi:10.3762/bjoc.9.306

• model [74][75]. The 3,3-difluoropyrrolidine moiety (e.g. 78) is found in a variety of enzyme inhibitors such as thrombin inhibitors and cathepsin inhibitors, and so this synthetic methodology (Scheme 10) is likely to have valuable future applications in medicinal chemistry. 6.6 Chemoenzymatic synthesis

Consecutive cross-coupling reactions of 2,2-difluoro-1-iodoethenyl tosylate with boronic acids: efficient synthesis of 1,1-diaryl-2,2-difluoroethenes

• Ju Hee Kim,
• Su Jeong Choi and
• In Howa Jeong

Beilstein J. Org. Chem. 2013, 9, 2470–2475, doi:10.3762/bjoc.9.286

• compounds [1][2][3][4], and their biological activity, such as mechanism-based enzyme inhibitors, in the area of medicinal chemistry [5][6][7][8]. The 1,1-difluoroethenylidene functionality in these compounds is also known to act as a bioisostere for the carbonyl group of many biologically active compounds

A one-pot synthesis of 3-trifluoromethyl-2-isoxazolines from trifluoromethyl aldoxime

• Raoni S. B. Gonçalves,
• Michael Dos Santos,
• Guillaume Bernadat,
• Danièle Bonnet-Delpon and
• Benoit Crousse

Beilstein J. Org. Chem. 2013, 9, 2387–2394, doi:10.3762/bjoc.9.275

• causes remarkable changes of their physicochemical properties, which allows the development of substances with improved pharmacological characteristics. Some examples are the synthesis of modified amino acids and peptides, carbohydrates, natural products and the development of more selective enzyme

• inhibitors [17][18][19][20][21]. Another powerful area, yet a somewhat less utilised role for fluorine is as a tag for 19F NMR that offers several analytical advantages including speed, sensitivity and selectivity [22][23]. Fluorinated molecules have served as valuable 19F NMR probes in high-throughput

Efficient regio- and stereoselective access to novel fluorinated β-aminocyclohexanecarboxylates

• Loránd Kiss,
• Melinda Nonn,
• Reijo Sillanpää,
• Santos Fustero and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2013, 9, 1164–1169, doi:10.3762/bjoc.9.130

• exhibit higher bioactivities than the nonfluorinated counterparts. The fluorinated α- or acyclic β-amino acids have acquired significance as antibacterial or antifungal agents, enzyme inhibitors or as antitumoral compounds. Introduction of a fluorinated amino acid into a peptide may generate specific

Conformational analysis and intramolecular interactions in monosubstituted phenylboranes and phenylboronic acids

• Josué M. Silla,
• Rodrigo A. Cormanich,
• Roberto Rittner and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2013, 9, 1127–1134, doi:10.3762/bjoc.9.125

• ; monosubstituted phenylboranes; phenylboronic acids; Introduction Boronic acid derivatives have been widely studied because of their good performance as pharmaceutical agents, serving in the development of enzyme inhibitors of peptidases/proteases, proteasomes, arginase, nitric oxide synthase (NOS), and

Methylidynetrisphosphonates: Promising C₁ building block for the design of phosphate mimetics

• Vadim D. Romanenko and
• Valery P. Kukhar

Beilstein J. Org. Chem. 2013, 9, 991–1001, doi:10.3762/bjoc.9.114

• heteroatom substituent at the bridged carbon atom permits both modulation of pKa values and hydrogen bonding, there is a need for profound study of α-functionalized trisphosphonate systems. Such compounds can be promising building blocks for the synthesis of false substrates or enzyme inhibitors involved in

Appel-reagent-mediated transformation of glycosyl hemiacetal derivatives into thioglycosides and glycosyl thiols

• Tamashree Ghosh,
• Abhishek Santra and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2013, 9, 974–982, doi:10.3762/bjoc.9.112

• enzymatic hydrolysis, several thioglycosides have been evaluated as enzyme inhibitors [13][14]. As a consequence a large number of reports have appeared in the past for the preparation of thioglycosides. Conventionally, thioglycosides are prepared by the reaction of glycosyl acetates with thiols or

A new synthetic access to 2-N-(glycosyl)thiosemicarbazides from 3-N-(glycosyl)oxadiazolinethiones and the regioselectivity of the glycosylation of their oxadiazolinethione precursors

• El Sayed H. El Ashry,
• El Sayed H. El Tamany,
• Mohy El Din Abdel Fattah,
• Mohamed R. E. Aly,
• Ahmed T. A. Boraei and
• Axel Duerkop

Beilstein J. Org. Chem. 2013, 9, 135–146, doi:10.3762/bjoc.9.16

• ]. Glycosylamines are used also as enzyme inhibitors and vaccine precursors [18][19][20][21], and in glycopeptide synthesis [22][23] and in glycodendrimers and glycoclusters [24][25]. There are four structural isomers of glycosyl-thiosemicarbazides according to the location of the glycosyl residue on the

Synthesis of chiral sulfoximine-based thioureas and their application in asymmetric organocatalysis

• Marcus Frings,
• Isabelle Thomé and
• Carsten Bolm

Beilstein J. Org. Chem. 2012, 8, 1443–1451, doi:10.3762/bjoc.8.164

• from medicinal chemistry where sulfoximines show potential as enzyme inhibitors [10][11][12][13][14], and from materials science where they were evaluated as functional building blocks [15]. In addition, sulfoximines are most present in synthetic organic chemistry for various reasons and recent

Low-generation dendrimers with a calixarene core and based on a chiral C₂-symmetric pyrrolidine as iminosugar mimics

• Marco Marradi,
• Stefano Cicchi,
• Francesco Sansone,
• Alessandro Casnati and
• Andrea Goti

Beilstein J. Org. Chem. 2012, 8, 951–957, doi:10.3762/bjoc.8.107

• occasionally, and their properties as multivalent enzyme inhibitors gave contrasting results. Early findings indicated in fact that poor multivalent phenomena take place [4][5][6], but more recently moderate [7] to remarkable [8][9] effects have been reported on glycosidases. Unlike lectin-mediated

Synthesis and biological evaluation of nojirimycin- and pyrrolidine-based trehalase inhibitors

• Davide Bini,
• Francesca Cardona,
• Matilde Forcella,
• Camilla Parmeggiani,
• Paolo Parenti,
• Francesco Nicotra and
• Laura Cipolla

Beilstein J. Org. Chem. 2012, 8, 514–521, doi:10.3762/bjoc.8.58

• the adjacent carbon, affords compounds less active than 9, but with reversed specificity (9 is twice more active on porcine trehalase, while 14, 16 and 20 are more active on insect enzyme). Conclusion The design and synthesis of enzyme inhibitors can often provide information about the mechanism of

α,β-Aziridinylphosphonates by lithium amide-induced phosphonyl migration from nitrogen to carbon in terminal aziridines

• David. M. Hodgson and
• Zhaoqing Xu

Beilstein J. Org. Chem. 2010, 6, 978–983, doi:10.3762/bjoc.6.110

• , antibacterial agents, enzyme inhibitors and herbicides [1][2][3]. α,β-Aziridinylphosphonates 3, while possessing biological activity themselves, can be converted into aminophosphonic acids using various ring-opening processes [4][5][6]. Aziridinylphosphonates 3 have previously been prepared by a variety of

Synthesis and binding studies of two new macrocyclic receptors for the stereoselective recognition of dipeptides

• Ana Maria Castilla,
• M. Morgan Conn and
• Pablo Ballester

Beilstein J. Org. Chem. 2010, 6, No. 5, doi:10.3762/bjoc.6.5

• of protein–protein interactions is gaining interest as they are known to play a critical role in important biological processes such as the normal function of cellular/organelle structure, immune response, enzyme inhibitors, signal transduction, and apoptosis. Rational protein surface recognition