Pyrrolidine nucleotide analogs with a tunable conformation

• Lenka Poštová Slavětínská,
• Dominik Rejman and
• Radek Pohl

Beilstein J. Org. Chem. 2014, 10, 1967–1980, doi:10.3762/bjoc.10.205

• , nucleosides and nucleobases play an important role in all biological systems. Therefore, it is not surprising that many of their analogs possess interesting biological properties. Potent antiviral drugs based on phosphonate nucleotides 1a–c [1][2], 2a–d and 3a–d (Figure 1) have been reported. Prodrugs of

• successful approach in developing antiviral therapeutics. Our long-term interest in the synthesis and evaluation of biological properties of phosphonate azanucleotides has yielded several potent inhibitors of nucleoside/nucleotide metabolizing enzymes: thymine derivatives 4 and 11 (Figure 1 and Figure 2

• thereof to an active site of a particular enzyme. The knowledge of the conformation of nucleosides, nucleotides and their analogs is therefore essential for the understanding or even prediction of their biological properties. There are several approaches providing information on the conformation of a five

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

• . This led to the development of stereoselective methodologies and the synthesis of compounds with various biological properties [1]. In particular, the high reactivity of the C-3 prochiral carbonyl group allows the easy transformation of isatin into 2-oxindole derivatives, mostly by nucleophilic

Design and synthesis of multivalent neoglycoconjugates by click conjugations

• Feiqing Ding,
• Li Ji,
• Ronny William,
• Hua Chai and
• Xue-Wei Liu

Beilstein J. Org. Chem. 2014, 10, 1325–1332, doi:10.3762/bjoc.10.134

• glycoscience, because triazole-linked glycoconjugates can exhibit very interesting biological properties, offering a convenient access toward oligosaccharides, glycopeptide mimics, or multivalent carbohydrate systems [40][41][42][43][44][45][46][47][48]. Their further application in molcecular biosystems is

Human dendritic cell activation induced by a permannosylated dendron containing an antigenic GM₃-lactone mimetic

• Renato Ribeiro-Viana,
• Elena Bonechi,
• Javier Rojo,
• Clara Ballerini,
• Giuseppina Comito,
• Barbara Richichi and
• Cristina Nativi

Beilstein J. Org. Chem. 2014, 10, 1317–1324, doi:10.3762/bjoc.10.133

• biological properties of the monovalent synthetic antigen as an immunomodulator as well as an anti-adhesive agent in melanoma progression. Taking into account all these data and relying on recent results on the use of mannose-based glycodendrons as vectors for antigen delivery to DCs [34], we report here on

A novel family of (1-aminoalkyl)(trifluoromethyl)- and -(difluoromethyl)phosphinic acids – analogues of α-amino acids

• Natalia V. Pavlenko,
• Tatiana I. Oos,
• Yurii L. Yagupolskii,
• Igor I. Gerus,
• Uwe Doeller and
• Lothar Willms

Beilstein J. Org. Chem. 2014, 10, 722–731, doi:10.3762/bjoc.10.66

• . Incorporation of fluorine or fluorinated moieties can be used for the alteration of physiological properties of many biologically significant substances. The changes of their biological properties caused by this fluorination are influenced by complex factors, however. The similarity of the diameters of fluorine

Integration of enabling methods for the automated flow preparation of piperazine-2-carboxamide

• Richard J. Ingham,
• Claudio Battilocchio,
• Joel M. Hawkins and
• Steven V. Ley

Beilstein J. Org. Chem. 2014, 10, 641–652, doi:10.3762/bjoc.10.56

• database for medicinal chemistry. For example, piperazine-2-carboxamide (1, Figure 2a) is an amino acid derivative with interesting biological properties [17]. At the time of writing, racemic 1 was identified as a notably expensive building block [18] and thus a good target for this transformation. We have

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• , these IMCRs provide linear products, whereas their cyclic analogues are highly desirable as discussed above for potentially improved structural and biological properties. Fortunately, these linear products can be cyclized via post-condensation transformations since a wide range of unreactive functional

• peptidomimetic design, the incorporation of N-protected aldehydes 4 (Scheme 2) is of great importance since deprotection of the α-adduct 5 allows acyl-migration and give access to α-hydroxy-β-amino amide derivatives 7 that possess important biological properties. This Passerini–amine deprotection–acyl migration

• may enhance the biological properties of target molecules and especially CF3-containing amino acids have demonstrated to be hydrolytically more stable as compared to the native amino acids [87]. In addition, the insertion of α-amino phosphonates to peptides has shown enhanced antibacterial, antivirus

Preparation of new alkyne-modified ansamitocins by mutasynthesis

• Kirsten Harmrolfs,
• Lena Mancuso,
• Binia Drung,
• Florenz Sasse and
• Andreas Kirschning

Beilstein J. Org. Chem. 2014, 10, 535–543, doi:10.3762/bjoc.10.49

• after reductive cleavage, ansamitocin derivative 8 still showed sufficient antiproliferative activity. This is in line with our observation that structural changes at the aromatic ring do not affect the biological properties of the ansamitocins to a great extent [13][14][15][16][17][18][19][20][21]. In

Direct and indirect single electron transfer (SET)-photochemical approaches for the preparation of novel phthalimide and naphthalimide-based lariat-type crown ethers

• Dae Won Cho,
• Patrick S. Mariano and
• Ung Chan Yoon

Beilstein J. Org. Chem. 2014, 10, 514–527, doi:10.3762/bjoc.10.47

• provided a solid foundation for the design of new strategies for the preparation of interesting members of the crown ether family. Substances that possess polyheteroatom-containing macrocyclic rings were carefully investigated owing to their interesting chemical and biological properties. Prime examples of

A catalyst-free multicomponent domino sequence for the diastereoselective synthesis of (E)-3-[2-arylcarbonyl-3-(arylamino)allyl]chromen-4-ones

• Pitchaimani Prasanna,
• Pethaiah Gunasekaran,
• Subbu Perumal and
• J. Carlos Menéndez

Beilstein J. Org. Chem. 2014, 10, 459–465, doi:10.3762/bjoc.10.43

• ; Introduction Chromones are widely present in nature, especially in the plant kingdom, and a wide variety of useful biological properties are associated with them [1][2]. Chromone derivatives act as effective tyrosine and protein kinase C inhibitors [3] and display antifungal [4][5], antimycobacterial [6

SF002-96-1, a new drimane sesquiterpene lactone from an Aspergillus species, inhibits survivin expression

• Silke Felix,
• Louis P. Sandjo,
• Till Opatz and
• Gerhard Erkel

Beilstein J. Org. Chem. 2013, 9, 2866–2876, doi:10.3762/bjoc.9.323

• transiently transfected Colo 320 cells. In the current study, the fermentation, structure elucidation, and some biological properties of the compound are described. Results and Discussion Identification and structure elucidation SF002-96-1 was obtained by a bio-guided isolation procedure as a colourless oil

Flow microreactor synthesis in organo-fluorine chemistry

• Hideki Amii,
• Aiichiro Nagaki and
• Jun-ichi Yoshida

Beilstein J. Org. Chem. 2013, 9, 2793–2802, doi:10.3762/bjoc.9.314

• development of materials and biologically active agents. The introduction of fluorine atoms into organic molecules often exerts influences upon physical, chemical, and biological properties [1][2][3][4][5][6][7][8]. Although the fluorine atom is larger than the hydrogen atom, the replacement of hydrogen by

The myxocoumarins A and B from Stigmatella aurantiaca strain MYX-030

• Tobias A. M. Gulder,
• Snežana Neff,
• Traugott Schüz,
• Tammo Winkler,
• René Gees and
• Bettina Böhlendorf

Beilstein J. Org. Chem. 2013, 9, 2579–2585, doi:10.3762/bjoc.9.293

• interesting biological properties are the myxobacteria [9][10][11][12]. These organisms are especially talented in assembling PKS-, NRPS- and PKS/NRPS-hybrid products, often incorporating unusual biochemistry in the respective biosynthetic pathways [13][14][15]. The most well-known myxobacterial natural

Recent advances in transition metal-catalyzed Csp²-monofluoro-, difluoro-, perfluoromethylation and trifluoromethylthiolation

• Grégory Landelle,
• Armen Panossian,
• Sergiy Pazenok,
• Jean-Pierre Vors and
• Frédéric R. Leroux

Beilstein J. Org. Chem. 2013, 9, 2476–2536, doi:10.3762/bjoc.9.287

• -fluorine; transition metal; trifluoromethylation; trifluoromethylthiolation; Review Introduction The incorporation of fluorine or fluorinated moieties into organic compounds plays a key role in Life-Science oriented research as often-profound changes of the physico-chemical and biological properties can

Synthesis of the spiroketal core of integramycin

• Evgeny. V. Prusov

Beilstein J. Org. Chem. 2013, 9, 2446–2450, doi:10.3762/bjoc.9.282

• octalin fragment [4] of integramycin were recently reported by Roush and Floreancig, however, a total synthesis of this rather complex natural product has yet to be accomplished. Intrigued by its biological properties and capitalizing on our previous experience [5] in the total synthesis of natural

Synthesis of enantiopure sugar-decorated six-armed triptycene derivatives

• Paola Bonaccorsi,
• Maria Luisa Di Gioia,
• Antonella Leggio,
• Lucio Minuti,
• Teresa Papalia,
• Carlo Siciliano,
• Andrea Temperini and
• Anna Barattucci

Beilstein J. Org. Chem. 2013, 9, 2410–2416, doi:10.3762/bjoc.9.278

• their biological properties [13][14]. Accordingly, we developed a methodology for obtaining molecules showing a rigid lipophilic core represented by the triptycene skeleton that is linked, by the arene rings, to six sugar moieties through six triazole units as spacers. To the best of our knowledge, this

Synthesis of homo- and heteromultivalent carbohydrate-functionalized oligo(amidoamines) using novel glyco-building blocks

• Felix Wojcik,
• Sinaida Lel,
• Alexander G. O’Brien,
• Peter H. Seeberger and
• Laura Hartmann

Beilstein J. Org. Chem. 2013, 9, 2395–2403, doi:10.3762/bjoc.9.276

• is well understood that the number and spacing of ligands have a tremendous influence on the resulting binding and thus biological properties [5][6][7]. Therefore, in order to understand and explore these interactions and their potential for biomedical applications, a more detailed look at the

Elucidation of the regio- and chemoselectivity of enzymatic allylic oxidations with Pleurotus sapidus – conversion of selected spirocyclic terpenoids and computational analysis

• Verena Weidmann,
• Mathias Schaffrath,
• Holger Zorn,
• Julia Rehbein and
• Wolfgang Maison

Beilstein J. Org. Chem. 2013, 9, 2233–2241, doi:10.3762/bjoc.9.262

• have other interesting biological properties such as phytotoxic activity. A few selected examples are depicted in Figure 2. In this paper, we report biocatalytic allylic oxidations of spirocyclic model compounds and of the natural product vitispirane with the lyophilisate of PSA. A rationalization of

Structure of 1,5-benzodiazepinones in the solid state and in solution: Effect of the fluorination in the six-membered ring

• Marta Pérez-Torralba,
• Rosa M. Claramunt,
• M. Ángeles García,
• Concepción López,
• M. Carmen Torralba,
• M. Rosario Torres,
• Ibon Alkorta and
• José Elguero

Beilstein J. Org. Chem. 2013, 9, 2156–2167, doi:10.3762/bjoc.9.253

• applications in medicinal chemistry [2][3][4][5][6], the most important is clobazam (7-chloro-1-methyl-5-phenyl-1H-1,5-benzodiazepine-2,4(3H,5H)-dione, Figure 1). As a continuation of our research program on the synthesis, spectroscopic and biological properties of 1,5-benzodiazepine derivatives as well as

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• representative members are depicted in Figure 5 [43]. Cyctochalasan alkaloids display a wide range of biological properties, such as cytotoxic, antimicrobial, antiviral and phytotoxic activities and were reviewed in detail by Hertweck in 2010 [44]. Structurally, they consist of one amino acid and a highly

• interesting biological properties, such as high antiviral activity (156) [141], inhibition of the HIV-1 protease (157) [132], antibacterial and antifungal activities (159–160) [133] or neuritogenic properties (161) [134]. So far, only a few total syntheses were accomplished and the exact biosynthetic pathways

A concise enantioselective synthesis of the guaiane sesquiterpene (−)-oxyphyllol

• Martin Zahel and
• Peter Metz

Beilstein J. Org. Chem. 2013, 9, 2028–2032, doi:10.3762/bjoc.9.239

• ; Introduction The hydroazulene framework is present in many natural products that are often associated with interesting biological properties [1][2]. The guaiane sesquiterpene (−)-oxyphyllol (1) has been isolated from the roots of the Thai medicinal plant Phyllanthus oxyphyllus [3]. A recent enantioselective

Structure elucidation of β-cyclodextrin–xylazine complex by a combination of quantitative ¹H–¹H ROESY and molecular dynamics studies

• Syed Mashhood Ali,
• Kehkeshan Fatma and
• Snehal Dhokale

Beilstein J. Org. Chem. 2013, 9, 1917–1924, doi:10.3762/bjoc.9.226

• the cavity is hydrophobic [2][3]. The encapsulation of a guest into the CD cavity has a profound effect on the chemical, physical and biological properties of the guest. The structure establishment of CD inclusion complexes in solution state is a challenging task considering the fact that the

Raman spectroscopy as a tool for monitoring mesoscale continuous-flow organic synthesis: Equipment interface and assessment in four medicinally-relevant reactions

• Trevor A. Hamlin and
• Nicholas E. Leadbeater

Beilstein J. Org. Chem. 2013, 9, 1843–1852, doi:10.3762/bjoc.9.215

• effect on the outcome of the reaction (Table 2, entries 3 and 4). The Claisen–Schmidt condensation We moved next to study the Claisen–Schmidt condensation of benzaldehyde with acetophenone to yield chalcone (Scheme 3). Chalcones display interesting biological properties such as antioxidant, cytotoxic

Synthesis and biological activities of the respiratory chain inhibitor aurachin D and new ring versus chain analogues

• Xu-Wen Li,
• Jennifer Herrmann,
• Yi Zang,
• Philippe Grellier,
• Soizic Prado,
• Rolf Müller and
• Bastien Nay

Beilstein J. Org. Chem. 2013, 9, 1551–1558, doi:10.3762/bjoc.9.176

• powerful inhibitors of the quinol oxidation sites of bacterial cytochromes bo and bd, with dissociation constants in the range of 10 nM. Aurachin D (4) was shown to selectively inhibit the cytochrome bd complex [12]. With such biological properties, aurachins and their analogues are also strong

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

• synthetic molecules, and they also possess potentially useful biological properties [17][18][19][20]. The benzopyran framework has attracted considerable attention because of the importance of chromans and their biological properties. Numerous synthetic routes have been reported over the past few decades