On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site

• Eirinaios I. Vrettos,
• Gábor Mező and
• Andreas G. Tzakos

Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80

• prodrug with enhanced plasma stability and/or cell permeability [27] and in the same time diminished toxicity for normal cells; c) covalent attachment of a drug on a tumor-targeting element (small molecule, peptide or antibody) able to selectively target and permeate cancer cells. The conjugation is being

Electrochemically modified Corey–Fuchs reaction for the synthesis of arylalkynes. The case of 2-(2,2-dibromovinyl)naphthalene

• Fabiana Pandolfi,
• Isabella Chiarotto and
• Marta Feroci

Beilstein J. Org. Chem. 2018, 14, 891–899, doi:10.3762/bjoc.14.76

• reaction under milder conditions. 2-Ethynylnaphthalene (2a) is a small molecule with a high and selective biological activity. In particular, this molecule has been demonstrated to be a selective inactivator of cytochrome P-450 2B4 [26] and an inhibitor also of other cytochrome P-450 isoforms [27]. We thus

Methyl isocyanide as a convertible functional group for the synthesis of spirocyclic oxindole γ-lactams via post-Ugi-4CR/transamidation/cyclization in a one-pot, three-step sequence

• Amarendar Reddy Maddirala and
• Peter R. Andreana

Beilstein J. Org. Chem. 2018, 14, 875–883, doi:10.3762/bjoc.14.74

• chromatography (EtOAc/hexanes) to yield pure compounds 8a–j. ORTEP diagram of compound 7a. Readily and synthetically accessible starting materials. Small molecule library of spiro[indoline-3,2'-pyrrolidine]-2,5'-dione analogs. Previously reported post-Ugi-4CR methods for the synthesis of 2-oxindoles and

Crystal structure of the inclusion complex of cholesterol in β-cyclodextrin and molecular dynamics studies

• Elias Christoforides,
• Andreas Papaioannou and
• Kostas Bethanis

Beilstein J. Org. Chem. 2018, 14, 838–848, doi:10.3762/bjoc.14.69

• XAMDEX [35]) are found to have a 2:1 host/guest stoichiometry. In all these cases, the shift between two successive dimers along the c-axis is 6.017, 6.22 and 6.27 Å, respectively. Thus they crystallize also in the IM packing mode. The first case (ANAXAP), concerns the inclusion of a small molecule model

An uracil-linked hydroxyflavone probe for the recognition of ATP

• Márton Bojtár,
• Péter Zoltán Janzsó-Berend,
• Dávid Mester,
• Dóra Hessz,
• Mihály Kállay,
• Miklós Kubinyi and
• István Bitter

Beilstein J. Org. Chem. 2018, 14, 747–755, doi:10.3762/bjoc.14.63

• made to selectively recognize and detect these analytes, especially ATP using small-molecule fluorescent chemosensors. Despite the various solutions, the selective detection of ATP is still challenging due to the structural similarity of various nucleotides. In this paper, we report the conjugation of

Nanoreactors for green catalysis

• M. Teresa De Martino,
• Loai K. E. A. Abdelmohsen,
• Floris P. J. T. Rutjes and
• Jan C. M. van Hest

Beilstein J. Org. Chem. 2018, 14, 716–733, doi:10.3762/bjoc.14.61

• catalysts are entrapped and physically separated in an isolated compartment has appeared to be an excellent facile approach to enhance performance of reactions in water [31][32][33][34]. Pioneering examples in this field include small molecule host–guest containers such as cavitands [35][36][37], and

• Pd catalyst together with a PAA (poly(acrylic acid)) based polymer self-assembled in water [32]. The catalytic activity of the nanostructures was compared to the results achieved with the small molecule analogues of the pincer Pd complex, in a Suzuki–Miyaura coupling. When the reaction of vinyl

• stabilized by colloidal particles that adsorb at the water–oil interface. They are more stable than classical emulsions and do not require the usage of small molecule surfactants. This is a big advantage in downstream processing and product and catalyst recovery. The enzyme Candida antarctica lipase B (CalB

Continuous multistep synthesis of 2-(azidomethyl)oxazoles

• Thaís A. Rossa,
• Nícolas S. Suveges,
• Marcus M. Sá,
• David Cantillo and
• C. Oliver Kappe

Beilstein J. Org. Chem. 2018, 14, 506–514, doi:10.3762/bjoc.14.36

• 1,4-disubstituted triazoles 8 through click reaction between 2-azidomethyl-4,5-diaryloxazoles and alkynes in the presence of a copper(I) catalyst (Scheme 2). The authors were able to synthesize an array of small-molecule peptidomimetics that inhibited Porphyromonas gingivalis biofilm formation [34

Synthesis and biological evaluation of RGD and isoDGR peptidomimetic-α-amanitin conjugates for tumor-targeting

• Lizeth Bodero,
• Paula López Rivas,
• Barbara Korsak,
• Torsten Hechler,
• Andreas Pahl,
• Christoph Müller,
• Daniela Arosio,
• Luca Pignataro,
• Cesare Gennari and
• Umberto Piarulli

Beilstein J. Org. Chem. 2018, 14, 407–415, doi:10.3762/bjoc.14.29

• α-amanitin activity on the targeted cells. An alternative approach to the antibody targeted therapy is represented by small molecule–drug conjugates (SMDCs), where the small molecule – usually a peptide or peptidomimetic receptor ligand – avoids the drawbacks of ADCs such as high manufacturing costs

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

• reported an effective ylide transfer reagent, which led to sulfonium ylide 6 [35][36][37][38]. As part of our ongoing efforts to discover small molecule modulators of protein–protein interactions (PPIs), we are particularly interested in coplanar compounds that mimic β-strand side-chain distributions [39

Polarization spectroscopy methods in the determination of interactions of small molecules with nucleic acids – tutorial

• Tamara Šmidlehner,
• Ivo Piantanida and
• Gennaro Pescitelli

Beilstein J. Org. Chem. 2018, 14, 84–105, doi:10.3762/bjoc.14.5

• paramount interest because many biological processes, drugs and biochemical tools/probes rely on them [7][8]. Due to the possibly multifaceted nature of the complex formed between a small-molecule ligand and a large receptor (DNA/RNA), several complementary methods are needed for the accurate

• in the UV–vis range of the electromagnetic spectrum, where electronic transitions occur. The application of these polarization spectroscopy methods for the study of a complex between a small molecule (ligand) and DNA or RNA can generally be divided into two wavelength ranges: a) monitoring changes in

• and, in addition, not all potential small-molecule binding sites on DNA-supercoiled fragments are accessible to the small molecule, therefore leading to erroneous site-size evaluation. 2.3. Ligand solution preparation and characterization Preferably, the ligand should be dissolved in aqueous solution

Hydrolysis, polarity, and conformational impact of C-terminal partially fluorinated ethyl esters in peptide models

• Vladimir Kubyshkin and
• Nediljko Budisa

Beilstein J. Org. Chem. 2017, 13, 2442–2457, doi:10.3762/bjoc.13.241

• incorporation of a fluorinated moiety into a modular peptide fragment is highly desirable. Several recent efforts have been made to achieve this goal [9][47]. Fluorinated diazoalkanes have shown particularly promising results in small molecule functionalization [48], and these have a potential to be used for

Exploring mechanochemistry to turn organic bio-relevant molecules into metal-organic frameworks: a short review

• Vânia André,
• Sílvia Quaresma,
• João Luís Ferreira da Silva and
• M. Teresa Duarte

Beilstein J. Org. Chem. 2017, 13, 2416–2427, doi:10.3762/bjoc.13.239

• steps: i) the synthesis of the framework and ii) the encapsulation of the small molecule by soaking and diffusion methods under mild conditions [96]. However, there are some one-pot syntheses reported for the encapsulation of small molecules into ZIF-8. Liédana et al. disclosed the in situ encapsulation

Solid-state mechanochemical ω-functionalization of poly(ethylene glycol)

• Michael Y. Malca,
• Pierre-Olivier Ferko,
• Tomislav Friščić and
• Audrey Moores

Beilstein J. Org. Chem. 2017, 13, 1963–1968, doi:10.3762/bjoc.13.191

• manufacturing, drug development and nanotechnology. PEG derivatives are being increasingly used to covalently modify small molecule and peptide drugs, as well as bioactive nanomaterials in order to improve solubility in biological serum, reduce immunogenicity, and enhance pharmacokinetic profiles. Herein we

• ], leading to significant improvements in blood circulation half-lives, decrease in clearance rates, and prolonged pharmacological effects [12][13][14]. Derivatives of PEG are often used to perform conjugation reactions on small molecule drugs, proteins, or bioactive nanomaterials [15]. Other methods include

• leading to unwanted chain lengthening during the derivatization process. Under mechanochemical conditions, diffusion limitation may favor the reactivity of small molecule reagents over the intermolecular reaction between two polymers to afford the kinetically-favorable end-products, in contrast to solvent

β-Cyclodextrin- and adamantyl-substituted poly(acrylate) self-assembling aqueous networks designed for controlled complexation and release of small molecules

• Liang Yan,
• Duc-Truc Pham,
• Philip Clements,
• Stephen F. Lincoln,
• Jie Wang,
• Xuhong Guo and
• Christopher J. Easton

Beilstein J. Org. Chem. 2017, 13, 1879–1892, doi:10.3762/bjoc.13.183

• , fluconazole [40] and curcumin [37], along with larger species exemplified by RNA and DNA segments [26][32][33][36][39][47]. Some systems are designed to target specific tissues [26][35]. We are particularly interested in the extent to which small molecule guest complexation and release characteristics may be

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

Beilstein J. Org. Chem. 2017, 13, 1828–1849, doi:10.3762/bjoc.13.178

• enabled the quantitative synthesis of (thio)ureas and guanidines without using bulk solvents and the generation of byproducts, but it has also been established as a means to develop "click-type" chemistry for these classes of compounds and the concept of small molecule desymmetrization. Moreover

Bifunctional organocatalysts for the asymmetric synthesis of axially chiral benzamides

• Ryota Miyaji,
• Yuuki Wada,
• Akira Matsumoto,
• Keisuke Asano and
• Seijiro Matsubara

Beilstein J. Org. Chem. 2017, 13, 1518–1523, doi:10.3762/bjoc.13.151

• resolution [42][43][44][45][46][47], desymmetrization [48][49][50][51][52][53][54], de novo annulation [55][56][57][58][59][60][61], and point-to-axial chirality transfer [58][59] (for reviews, see references [31][62][63]), motivated us to expand on the utility of this class of small-molecule catalysts. We

2-Methyl-2,4-pentanediol (MPD) boosts as detergent-substitute the performance of ß-barrel hybrid catalyst for phenylacetylene polymerization

• Julia Kinzel,
• Daniel F. Sauer,
• Marco Bocola,
• Marcus Arlt,
• Tayebeh Mirzaei Garakani,
• Andreas Thiel,
• Klaus Beckerle,
• Tino Polen,
• Jun Okuda and
• Ulrich Schwaneberg

Beilstein J. Org. Chem. 2017, 13, 1498–1506, doi:10.3762/bjoc.13.148

• stabilization agents to solubilize purified transmembrane proteins is crucial for their application in aqueous media. The small molecule 2-methyl-2,4-pentanediol (MPD) was used to stabilize the transmembrane protein Ferric hydroxamate uptake protein component A (FhuA) utilized as host for the construction of a

• selectivity [13]. The membrane protein FhuA ΔCVFtev in MPD shows stability for more than three days under the reaction conditions and therefore is leading to significantly increased yields. Conclusion In conclusion, we successfully demonstrated the use of MPD as small-molecule stabilizer for utilization of

Synthesis of oligonucleotides on a soluble support

• Harri Lönnberg

Beilstein J. Org. Chem. 2017, 13, 1368–1387, doi:10.3762/bjoc.13.134

• phosphotriester chemistry The pioneering syntheses of ONs on a soluble support were carried out by the phosphotriester strategy. Although this coupling chemistry is seldom used on a solid support where small molecule reagents and wastes can be removed by simple washing, the avoidance of the oxidation step due to

• coupling was carried out in dioxane in the presence of NMI. Precipitations were achieved by 10-fold dilution with MeOH. All small-molecule compounds remained in solution. Removal of the 2-chlorophenyl protections with the tetramethylguanidium salt of (E)-2-nitrobenzaldoxime in aqueous dioxane, followed by

• elongation. Ethylthiotetrazole-activated coupling (3 equiv per OH) in MeCN was followed by sulfurization with phenylacetyl disulfide in pyridine. All small molecule compounds were removed by the so-called diafiltration through a polybenzimidazole-based membrane PBI-17DBX [71][72]. In other words, the volume

Biomimetic molecular design tools that learn, evolve, and adapt

• David A Winkler

Beilstein J. Org. Chem. 2017, 13, 1288–1302, doi:10.3762/bjoc.13.125

• purity of a chemical synthesis. Reprinted with permission from [36]; copyright 2016 Macmillan Publishers Ltd. (Top) Photograph of a small-molecule synthesizer comprised of three modules for deprotection, coupling, and purification steps. (Bottom) Natural products, materials, pharmaceuticals, and

• synthesis and analysis under computer control [35]. Another very recent and important step towards general automated chemical synthesis was reported in Science in 2015 (Figure 9) [37]. This platform provided a proof of concept of a general and broadly accessible automated solution to the problems of small

• -molecule synthesis. These technologies have now made practical the autonomous evolution of materials, where the design-synthesis-testing cycle is run by algorithmic evolutionary control and implemented robotically. In order to achieve autonomous algorithmic control, it is necessary to translate the

Glycoscience@Synchrotron: Synchrotron radiation applied to structural glycoscience

• Serge Pérez and
• Daniele de Sanctis

Beilstein J. Org. Chem. 2017, 13, 1145–1167, doi:10.3762/bjoc.13.114

• molecular crystals of micrometric dimensions or in the form of polycrystalline materials. Small molecule crystals In the quest to solve the crystal structures of cello-oligosaccharides, as model compounds of cellulose, several attempts to grow crystals of β-D-cellotetraose of a size suitable for X-ray

From chemical metabolism to life: the origin of the genetic coding process

• Antoine Danchin

Beilstein J. Org. Chem. 2017, 13, 1119–1135, doi:10.3762/bjoc.13.111

• organise and rule the flow of information that is key to life. The synthesis of macromolecules requires an abundant supply of basic building blocks produced by metabolism. Up to this point, we have followed Dyson’s reasoning. We have assumed that small-molecule metabolism progressively improved

Dynamics and interactions of ibuprofen in cyclodextrin nanosponges by solid-state NMR spectroscopy

• Monica Ferro,
• Franca Castiglione,
• Nadia Pastori,
• Carlo Punta,
• Lucio Melone,
• Walter Panzeri,
• Barbara Rossi,
• Francesco Trotta and
• Andrea Mele

Beilstein J. Org. Chem. 2017, 13, 182–194, doi:10.3762/bjoc.13.21

• . Ibuprofen is a small molecule characterized by an interesting internal dynamic behaviour due to two main molecular fragments: the alkyl chain and the aromatic ring. The internal motion was studied in detail using solid-state 13C NMR spectroscopy at different temperatures by Carignani et al. [25]. The

A new class of organogelators based on triphenylmethyl derivatives of primary alcohols: hydrophobic interactions alone can mediate gelation

• Wangkhem P. Singh and
• Rajkumar S. Singh

Beilstein J. Org. Chem. 2017, 13, 138–149, doi:10.3762/bjoc.13.17

• unit which may be further exploited in the design of small molecule based gelators. Keywords: hydrophobic interactions; organogelator; SEM; triphenylmethyl group; xerogel; Introduction Small organic molecules capable of forming gels are called low molecular weight gelators (LMWGs) [1][2][3]. These

New approaches to organocatalysis based on C–H and C–X bonding for electrophilic substrate activation

• Pavel Nagorny and
• Zhankui Sun

Beilstein J. Org. Chem. 2016, 12, 2834–2848, doi:10.3762/bjoc.12.283

• design of small molecule-based catalysts mimicking enzymatic function. A significant number of such efforts has been dedicated to designing new catalysts to enhance the electrophilicity of organic molecules through non-covalent interactions, and many important areas of organocatalysis have emerged from

• examples demonstrate the effectiveness of such interactions for organocatalyst design. While C–H···A hydrogen bonds have been invoked in biological processes, halogen bonding is not commonly observed in natural enzyme-catalyzed reactions. Therefore, application of these new interactions for small molecule

Synthesis of spiro[isoindole-1,5’-isoxazolidin]-3(2H)-ones as potential inhibitors of the MDM2-p53 interaction

• Salvatore V. Giofrè,
• Santa Cirmi,
• Raffaella Mancuso,
• Francesco Nicolò,
• Giuseppe Lanza,
• Laura Legnani,
• Agata Campisi,
• Maria A. Chiacchio,
• Michele Navarra,
• Bartolo Gabriele and
• Roberto Romeo

Beilstein J. Org. Chem. 2016, 12, 2793–2807, doi:10.3762/bjoc.12.278

• overexpression of MDM2 which suppresses the functions of the p53 protein [5][6][7][8]. The design of non-peptide, small-molecule inhibitors that block the MDM2-p53 interaction has been sought as an attractive strategy to activate p53 for the treatment of cancer and other human diseases [9][10][11]. Major

• advances have been made in the design of lipophilic small-molecule inhibitors of the MDM2-p53 interaction in recent years, and several compounds have moved into advanced preclinical development or clinical trials [12][13][14]. Potent MDM2-p53 inhibitors, such as Nutlin-3 [12] and the spirooxindoles, for