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

• and complex natural products and also of biologically active compounds. The phosphonamide anions are derived from a small number of common motifs as shown in Figure 1. Diazaphospholidine 2 was introduced by Hanessian and co-workers, and represents the most commonly used phosphonamide in organic

• on the application of phosphonamide reagents in the total synthesis of natural products and biologically active compounds. An overview of the molecules synthesized by phosphonamide technology is shown in Figure 2. Each molecule shown will be discussed in detail later in this review. First, relevant

Synthesis of trifluoromethyl-substituted pyrazolo[4,3-c]pyridines – sequential versus multicomponent reaction approach

• Barbara Palka,
• Angela Di Capua,
• Maurizio Anzini,
• Gyté Vilkauskaité,
• Algirdas Šačkus and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2014, 10, 1759–1764, doi:10.3762/bjoc.10.183

• -substituted pyrazolo[4,3-c]pyridines. The latter heterocyclic system represents the core of several biologically active compounds, acting, for instance, as SSAO inhibitors [10], or inhibitors of different kinases (LRRK2 [11][12], TYK2 [13], JAK [14][15]). Results and Discussion Chemistry The construction of

Streptopyridines, volatile pyridine alkaloids produced by Streptomyces sp. FORM5

• Ulrike Groenhagen,
• Michael Maczka,
• Jeroen S. Dickschat and
• Stefan Schulz

Beilstein J. Org. Chem. 2014, 10, 1421–1432, doi:10.3762/bjoc.10.146

• unique compounds may thus be used as a method to select microbial strains for the detection of non-volatile biologically active compounds. Alternatively, two independent gene clusters may be responsible for streptazolin and streptopyridines. The production of strain specific compounds connected to, e.g

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

4-Hydroxy-6-alkyl-2-pyrones as nucleophilic coupling partners in Mitsunobu reactions and oxa-Michael additions

• Michael J. Burns,
• Thomas O. Ronson,
• Richard J. K. Taylor and
• Ian J. S. Fairlamb

Beilstein J. Org. Chem. 2014, 10, 1159–1165, doi:10.3762/bjoc.10.116

• , which are found embedded in a number of natural products. Keywords: heterocycles; Mitsunobu reaction; oxa-Michael addition; 2-pyrone; vinyl ethers; Introduction The 2-pyrone motif is a prevalent structural feature of many complex natural products and biologically active compounds [1][2]. Various

Synthesis of (2S,3R)-3-amino-2-hydroxydecanoic acid and its enantiomer: a non-proteinogenic amino acid segment of the linear pentapeptide microginin

• Rajendra S. Rohokale and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2014, 10, 667–671, doi:10.3762/bjoc.10.59

• -hydroxy-β-amino acid) in 2a is present in several biologically active compounds such as taxol, balanol and bestatin. Therefore, this methodology could be potentially exploited for the synthesis of the chiral segment of these compounds. Microginin (1) and (2S,3R)-AHDA (2a). Retrosynthetic analysis of AHDA

Visible-light photoredox catalysis enabled bromination of phenols and alkenes

• Yating Zhao,
• Zhe Li,
• Chao Yang,
• Run Lin and
• Wujiong Xia

Beilstein J. Org. Chem. 2014, 10, 622–627, doi:10.3762/bjoc.10.53

• ; visible light; Introduction Bromophenols serve as important synthetic intermediates for a variety of naturally occurring biologically active compounds and are also important constituents of industrial chemicals [1][2][3][4][5]. Thus, numerous methods were developed for the electrophilic bromination of

The Flögel-three-component reaction with dicarboxylic acids – an approach to bis(β-alkoxy-β-ketoenamides) for the synthesis of complex pyridine and pyrimidine derivatives

• Mrinal K. Bera,
• Moisés Domínguez,
• Paul Hommes and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 394–404, doi:10.3762/bjoc.10.37

• dihydropyrimidinones or the corresponding dihydropyrimidinethiones. Due to their general importance (e.g. as biologically active compounds) the development of efficient protocols for the preparation of functionalized pyridine [10][11][12][13][14][15][16][17][18][19][20] and pyrimidine derivatives [21][22][23][24][25

One-pot synthesis of cyanohydrin derivatives from alkyl bromides via incorporation of two one-carbon components by consecutive radical/ionic reactions

• Shuhei Sumino,
• Akira Fusano,
• Hiroyuki Okai,
• Takahide Fukuyama and
• Ilhyong Ryu

Beilstein J. Org. Chem. 2014, 10, 150–154, doi:10.3762/bjoc.10.12

• formylation. Thus, we thought that the two step radical/ionic reactions can be extended to the consecutive C–C bond forming reactions. Cyanohydrins are important subunits frequently found in biologically active compounds and are also versatile building blocks for further synthetic transformations [20][21

Multicomponent reactions II

• Thomas J. J. Müller

Beilstein J. Org. Chem. 2014, 10, 115–116, doi:10.3762/bjoc.10.7

• . Biologically active compounds and photonic properties are addressed as well as mechanistic studies and models. The interested reader – whether an expert in the field or a newcomer – will find exciting reports from the current realm of MCR chemistry. As the guest editor of this Thematic Series I cordially thank

Diastereoselectivity in the Staudinger reaction of pentafluorosulfanylaldimines and ketimines

• Alexander Penger,
• Cortney N. von Hahmann,
• Alexander S. Filatov and
• John T. Welch

Beilstein J. Org. Chem. 2013, 9, 2675–2680, doi:10.3762/bjoc.9.303

• number of different ylides [16]. The reactions of α-pentafluorosulfanyl carbonyl compounds are governed by a combination of the substantial dipole moment and unique steric effects of the octahedral SF5 group. Aliphatic SF5-containing derivatives of biologically active compounds are not well-known. One

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

Synthesis and characterization of novel bioactive 1,2,4-oxadiazole natural product analogs bearing the N-phenylmaleimide and N-phenylsuccinimide moieties

• Catalin V. Maftei,
• Elena Fodor,
• Peter G. Jones,
• M. Heiko Franz,
• Gerhard Kelter,
• Heiner Fiebig and
• Ion Neda

Beilstein J. Org. Chem. 2013, 9, 2202–2215, doi:10.3762/bjoc.9.259

• heterocyclic 1,2,4-oxadiazole motif is of synthetic and pharmacological interest. It also forms an important constituent of biologically active compounds including natural products [1]. Sawyer et al. have described such compounds as bioisosteres for amides and esters [2], with the 1,2,4-oxadiazoles showing

Synthesis of enantiomerically pure N-(2,3-dihydroxypropyl)arylamides via oxidative esterification

• Akula Raghunadh,
• Satish S More,
• T. Krishna Chaitanya,
• Yadla Sateesh Kumar,
• Suresh Babu Meruva,
• L. Vaikunta Rao and
• U. K. Syam Kumar

Beilstein J. Org. Chem. 2013, 9, 2129–2136, doi:10.3762/bjoc.9.250

• purity was observed. Keywords: N-(2,3-dihydroxypropyl)arylamide; nitrogen heterocyclic carbenes (NHC); oxidative esterification of aromatic aldehyde; Introduction Chiral structures with three carbons are an integral part of many biologically active compounds including alkaloids, pharmaceuticals and

Synthesis of enantiomerically pure (2S,3S)-5,5,5-trifluoroisoleucine and (2R,3S)-5,5,5-trifluoro-allo-isoleucine

• Holger Erdbrink,
• Elisabeth K. Nyakatura,
• Susanne Huhmann,
• Ulla I. M. Gerling,
• Dieter Lentz,
• Beate Koksch and
• Constantin Czekelius

Beilstein J. Org. Chem. 2013, 9, 2009–2014, doi:10.3762/bjoc.9.236

• , extremely low polarizability and the strongest inductive effect among all chemical elements [1], fluorine substitution has become a powerful tool for modulating the properties of pharmaceuticals and biologically active compounds. In this respect, the incorporation of amino acids with fluorinated side chains

The first example of the Fischer–Hepp type rearrangement in pyrimidines

• Inga Cikotiene,
• Mantas Jonusis and
• Virginija Jakubkiene

Beilstein J. Org. Chem. 2013, 9, 1819–1825, doi:10.3762/bjoc.9.212

• preparation of condensed pyrimidine derivatives [27][28], have an interesting crystal structures [29][30][31], can be useful as bidentate ligands [32][33][34], and represent a class of biologically active compounds [35][36][37][38][39]. Results and Discussion The starting compounds 1 were prepared by the

Coupling of C-nitro-NH-azoles with arylboronic acids. A route to N-aryl-C-nitroazoles

• Marta K. Kurpet,
• Aleksandra Dąbrowska,
• Małgorzata M. Jarosz,
• Katarzyna Kajewska-Kania,
• Nikodem Kuźnik and
• Jerzy W. Suwiński

Beilstein J. Org. Chem. 2013, 9, 1517–1525, doi:10.3762/bjoc.9.173

• of cancer [7], or as antiphlogistic drugs [8]. Many derivatives of C-nitroazoles, particularly N-alkylnitroimidazoles being the most often repeating subunit in biologically active compounds, suffer from mutagenic and carcinogenic properties [9]. Therefore the efforts of several research groups are

Efficient continuous-flow synthesis of novel 1,2,3-triazole-substituted β-aminocyclohexanecarboxylic acid derivatives with gram-scale production

• Sándor B. Ötvös,
• Ádám Georgiádes,
• István M. Mándity,
• Lóránd Kiss and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2013, 9, 1508–1516, doi:10.3762/bjoc.9.172

• synthesis of a series of novel 1,2,3-triazole-modified β-aminocyclohexanecarboxylic acid derivatives as potential biologically active compounds. Gram-scale production is also reported, which predicts a possible usefulness for the pharmaceutical industry. Results and Discussion Several approaches are to be

Diastereoselective radical addition to γ-alkyl-α-methylene-γ-butyrolactams and the synthesis of a chiral pyroglutamic acid derivative

• Tomoko Yajima,
• Eriko Yoshida and
• Masako Hamano

Beilstein J. Org. Chem. 2013, 9, 1432–1436, doi:10.3762/bjoc.9.161

• acid derivative; radical alkylation; Introduction γ-Lactams exist in many natural products and biologically active compounds and are one of the most important classes of compounds for drug discovery [1][2][3]. Substituted γ-lactams, in particular, have potential application in drug synthesis, but the

Anionic cascade reactions. One-pot assembly of (Z)-chloro-exo-methylenetetrahydrofurans from β-hydroxyketones

• István E. Markó and
• Florian T. Schevenels

Beilstein J. Org. Chem. 2013, 9, 1319–1325, doi:10.3762/bjoc.9.148

• addition of 9 then affords the intermediate 10, which undergoes a 5-exo-dig cyclisation, ultimately yielding the observed (Z)-chloro-exo-methylenetetrahydrofuran 6. This structural motif constitutes the core of several biologically active compounds, including antimicrobial agents, fungicides and

• some of these dimeric products form the core of interesting biologically active compounds and of unique natural products. Experimental General procedure for the synthesis of chloromethylenefurans To 40 mL of anhydrous THF, cooled to 0 °C, 1.2 mL (15.0 mmol, 2.5 equiv) of dichloroethylene and 3.37 g of

Mild and efficient cyanuric chloride catalyzed Pictet–Spengler reaction

• Ashish Sharma,
• Mrityunjay Singh,
• Nitya Nand Rai and
• Devesh Sawant

Beilstein J. Org. Chem. 2013, 9, 1235–1242, doi:10.3762/bjoc.9.140

• . We demonstrated application of this methodology for the synthesis of tetrahydro-β-carbolines 3 and indolo[1,2-a]quinoxalines 8. These scaffolds are present in numerous biologically active compounds. Nevertheless, TCT is inexpensive and readily available. Therefore, this methodology can be easily

Catalytic asymmetric tandem Friedel–Crafts alkylation/Michael addition reaction for the synthesis of highly functionalized chromans

• Jiahuan Peng and
• Da-Ming Du

Beilstein J. Org. Chem. 2013, 9, 1210–1216, doi:10.3762/bjoc.9.137

• stereogenic centers [1][2][3][4][5][6][7][8][9][10][11][12][13]. Newly developed tandem/domino reactions are increasingly applied in the synthesis of natural products and other biologically active compounds [14][15][16]. Dihydrocoumarins, chromans, and chromenes can be found in many natural products and

Tandem dinucleophilic cyclization of cyclohexane-1,3-diones with pyridinium salts

• Mostafa Kiamehr,
• Firouz Matloubi Moghaddam,
• Satenik Mkrtchyan,
• Volodymyr Semeniuchenko,
• Linda Supe,
• Alexander Villinger,
• Peter Langer and
• Viktor O. Iaroshenko

Beilstein J. Org. Chem. 2013, 9, 1119–1126, doi:10.3762/bjoc.9.124

• ring is an essential building block for numerous natural products, synthetic pharmaceuticals, and various biologically active compounds [17]. The tetrahydropyridine scaffold is inherent for pharmacologically relevant representatives [18][19][20][21][22][23][24]. At the same time, heterocyclic systems

Use of 3-[¹⁸F]fluoropropanesulfonyl chloride as a prosthetic agent for the radiolabelling of amines: Investigation of precursor molecules, labelling conditions and enzymatic stability of the corresponding sulfonamides

• Reik Löser,
• Steffen Fischer,
• Achim Hiller,
• Martin Köckerling,
• Uta Funke,
• Aurélie Maisonial,
• Peter Brust and
• Jörg Steinbach

Beilstein J. Org. Chem. 2013, 9, 1002–1011, doi:10.3762/bjoc.9.115

• address biomolecular targets in vivo, requires a carefully developed methodology as the carbon–fluorine bond is rather difficult to tie [3][4]. Furthermore, as fluorine appears less frequently in biologically active compounds, molecules that show the potential to interact with certain imaging targets have

Simple synthesis of pyrrolo[3,2-e]indole-1-carbonitriles

• Adam Trawczyński,
• Robert Bujok,
• Zbigniew Wróbel and
• Krzysztof Wojciechowski

Beilstein J. Org. Chem. 2013, 9, 934–941, doi:10.3762/bjoc.9.107

• position 2 with electron-withdrawing groups. Keywords: alkylation; ketones; nitriles; pyrroloindole; reduction; trimethylchlorosilane; Introduction Indole and its analogues bearing condensed arene and heteroarene rings are privileged structures amongst biologically active compounds. The 1,2