Synthesis of non-racemic 4-nitro-2-sulfonylbutan-1-ones via Ni(II)-catalyzed asymmetric Michael reaction of β-ketosulfones

• Alexander N. Reznikov,
• Anastasiya E. Sibiryakova,
• Marat R. Baimuratov,
• Eugene V. Golovin,
• Victor B. Rybakov and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2019, 15, 1289–1297, doi:10.3762/bjoc.15.127

• cytotoxicity [9]. However, it is of great importance to obtain all stereoisomers for the study of biological activity. Therefore, the development of methods for the asymmetric synthesis of polyfunctional sulfones is valuable. The most notable of them are Ag- and Cu-catalyzed 1,3-dipolar cycloaddition reactions

Doebner-type pyrazolopyridine carboxylic acids in an Ugi four-component reaction

• Maryna V. Murlykina,
• Oleksandr V. Kolomiets,
• Maryna M. Kornet,
• Yana I. Sakhno,
• Sergey M. Desenko,
• Victoriya V. Dyakonenko,
• Svetlana V. Shishkina,
• Oleksandr A. Brazhko,
• Vladimir I. Musatov,
• Alexander V. Tsygankov,
• Erik V. Van der Eycken and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2019, 15, 1281–1288, doi:10.3762/bjoc.15.126

• discovery. The target products containing a heterocyclic core bound to a peptide-like chain also showed a broad spectrum of biological activity: β-secretase (BACE1) inhibitory activity [15]; inducing apoptosis in colorectal cancer cells [16]; antimalarial activity against a chloroquine (CQ) non-resistant

• with potential biological activity" (0119U100716). We thank Dr. E. Muravyouva for measuring the part of LC–MS spectra.

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• lateritium (causal agent of chlorotic leaf distortion in sweet potato) and Fusarium virguliforme (causal agent of sudden death syndrome in soy bean), without exerting in vitro toxicity on mammalian cells. Another interesting result came out from the comparison of the biological activity between homologous

• pairs 18 and 19 [22]. For example, the pair of androstanic and pregnanic derivatives incorporating R1 = Phe and R2 = t-Bu showed significant activity against both fungi tested, but the compounds derived from benzylamine (i.e., R1 = Bn) did exhibit either a low or null biological activity for the fungi

• Passerini and Ugi reactions. 3 Synthesis of steroid-fused heterocycles The modification of the steroidal nucleus by attaching a heterocycle to this hydrophobic scaffold has been traditionally used as an effective way to modulate the biological activity of these biomolecules. In this regard, pentacyclic

Novel (2-amino-4-arylimidazolyl)propanoic acids and pyrrolo[1,2-c]imidazoles via the domino reactions of 2-amino-4-arylimidazoles with carbonyl and methylene active compounds

• Victoria V. Lipson,
• Tetiana L. Pavlovska,
• Nataliya V. Svetlichnaya,
• Anna A. Poryvai,
• Nikolay Yu. Gorobets,
• Erik V. Van der Eycken,
• Irina S. Konovalova,
• Svetlana V. Shiskina,
• Alexander V. Borisov,
• Vladimir I. Musatov and
• Alexander V. Mazepa

Beilstein J. Org. Chem. 2019, 15, 1032–1045, doi:10.3762/bjoc.15.101

• of the projects "Creation of modern bases for obtaining and analyzing substances and components of materials for pharmaceutical purposes" (0119U100727) and "Investigation of structural features of nitrogen containing heterocycles with potential biological activity" (0119U100716).

Synthesis and biological investigation of (+)-3-hydroxymethylartemisinin

• Toni Smeilus,
• Farnoush Mousavizadeh,
• Johannes Krieger,
• Xingzhao Tu,
• Marcel Kaiser and
• Athanassios Giannis

Beilstein J. Org. Chem. 2019, 15, 567–570, doi:10.3762/bjoc.15.51

• artemisinin synthesis that addresses these challenges and pave the way for derivatization of the (+)-artemisinin skeleton at positions not accessible using current methodology [14]. Based on our approach we report here on the synthesis and biological activity of the title compound (+)-3

Synthesis and fluorescent properties of N(9)-alkylated 2-amino-6-triazolylpurines and 7-deazapurines

• Andrejs Šišuļins,
• Jonas Bucevičius,
• Yu-Ting Tseng,
• Irina Novosjolova,
• Kaspars Traskovskis,
• Ērika Bizdēna,
• Huan-Tsung Chang,
• Sigitas Tumkevičius and
• Māris Turks

Beilstein J. Org. Chem. 2019, 15, 474–489, doi:10.3762/bjoc.15.41

• biocompatibility could be applied for the cell staining in fluorescence microscopy. Applications in the cell studies The newly prepared compound library with purine and 7-deazapurine derivatives was submitted to the screening of their biological activity. The compounds of interest were studied on two cancer cell

Reusable and highly enantioselective water-soluble Ru(II)-Amm-Pheox catalyst for intramolecular cyclopropanation of diazo compounds

• Hamada S. A. Mandour,
• Yoko Nakagawa,
• Masaya Tone,
• Hayato Inoue,
• Nansalmaa Otog,
• Ikuhide Fujisawa,
• Soda Chanthamath and
• Seiji Iwasa

Beilstein J. Org. Chem. 2019, 15, 357–363, doi:10.3762/bjoc.15.31

• nature and have excellent biological activity, including strong antibiotic, antihelmetic, antifungal, antitumor, antiviral and anti-inflammatory, which make them interesting lead structures for new drugs [34]. That is why a great deal of attention has been paid to the synthesis of the lactone ring [35

Chemical structure of cichorinotoxin, a cyclic lipodepsipeptide that is produced by Pseudomonas cichorii and causes varnish spots on lettuce

• Hidekazu Komatsu,
• Takashi Shirakawa,
• Takeo Uchiyama and
• Tsutomu Hoshino

Beilstein J. Org. Chem. 2019, 15, 299–309, doi:10.3762/bjoc.15.27

• treatment had no activity, supporting that a macrocyclic peptide would be essential for biological activity. The sequence Z-dhThr17-D-alloThr18 of cichorinotoxin was converted to Z-dhThr17-E-dhThr18 by alkaline hydrolysis. This additional structural modification may have further decreased the activity

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• biological activity. Indeed, the interest in 3-hydroxyglutamic acid started many years ago by the discovery of this amino acid in hydrolysates of an antibiotic peptide S-520 [24]. It has been proved recently that it was actually the isomer (2S,3R)-2 and it is a fragment of a cyclohexapeptide [25]. (2R,3S)-2

• ][44]. Natural occurrence as well as possibilities of glutamate-like biological activity modulated by additional hydrogen bonding with hydroxy groups inspired the interest in the synthesis of stereoisomers of hydroxyglutamic acids 2–4 (Figure 2). Since they contain two or three stereogenic centers

• group in (2S,3S,4R)-127 followed by acidic hydrolysis gave (+)-polyoxamic acid [113]. Conclusion The synthesis of nonracemic hydroxyglutamic acids is an active area of research and it was stimulated by studies on glutamate receptors to modulate the biological activity of L-glutamic acid from one side

Synthesis and biological activity of methylated derivatives of the Pseudomonas metabolites HHQ, HQNO and PQS

• Sven Thierbach,
• Max Wienhold,
• Susanne Fetzner and
• Ulrich Hennecke

Beilstein J. Org. Chem. 2019, 15, 187–193, doi:10.3762/bjoc.15.18

Mn-mediated sequential three-component domino Knoevenagel/cyclization/Michael addition/oxidative cyclization reaction towards annulated imidazo[1,2-a]pyridines

• Olga A. Storozhenko,
• Alexey A. Festa,
• Delphine R. Bella Ndoutoume,
• Alexander V. Aksenov,
• Alexey V. Varlamov and
• Leonid G. Voskressensky

Beilstein J. Org. Chem. 2018, 14, 3078–3087, doi:10.3762/bjoc.14.287

• the redox potentials of three or more reactants at a time and employment of a sequential one-pot strategy may become one of the reasonable solutions. The vast biological activity of the compounds, bearing the imidazo[1,2-a]pyridine scaffold makes this heterocycle of great importance to the fields of

N-Acylated amino acid methyl esters from marine Roseobacter group bacteria

• Hilke Bruns,
• Lisa Ziesche,
• Nargis Khakin Taniwal,
• Laura Wolter,
• Thorsten Brinkhoff,
• Jennifer Herrmann,
• Rolf Müller and
• Stefan Schulz

Beilstein J. Org. Chem. 2018, 14, 2964–2973, doi:10.3762/bjoc.14.276

• of water, an intense ion due to loss of methanol, and loss of the carbomethoxy group [24]. Often the amino acid ion can also be observed. These features indicate the presence of an amino acid methyl ester. Biological activity Several of the synthesized compounds were tested in a broader screening

Protein–protein interactions in bacteria: a promising and challenging avenue towards the discovery of new antibiotics

• Laura Carro

Beilstein J. Org. Chem. 2018, 14, 2881–2896, doi:10.3762/bjoc.14.267

• features of the ligands, the discovery strategy, the characterization assay, the biological activity, and, if applicable, the SAR are discussed. Review Protein–protein interactions Due to the fact that protein–protein interactions (PPIs) play a pivotal role in many cellular processes, they have

Synthesis of mono-functionalized S-diazocines via intramolecular Baeyer–Mills reactions

• Miriam Schehr,
• Daniel Hugenbusch,
• Tobias Moje,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2018, 14, 2799–2804, doi:10.3762/bjoc.14.257

• field in medicine aiming at the development of drugs whose biological activity can be controlled with light [1][2][3][4]. There are several reported pharmacologically active compounds containing azobenzenes as photoswitchable units [5][6][7]. In most cases these drugs are active in the more stable trans

Synthesis and biological evaluation of 1,2-disubstituted 4-quinolone analogues of Pseudonocardia sp. natural products

• Stephen M. Geddis,
• Teodora Coroama,
• Suzanne Forrest,
• James T. Hodgkinson,
• Martin Welch and
• David R. Spring

Beilstein J. Org. Chem. 2018, 14, 2680–2688, doi:10.3762/bjoc.14.245

• transposition, whilst 4, 7 and 8 were derivatised from 1. In this current work, we turn to the further elucidation of the biological activity of this class of compounds. In order to gain additional insight into the associated structure–activity relationships (SAR), it was desired to generate analogues of the

• heterocyclisation with concomitant N–>N’ methyl transfer. With the library of natural products and analogues in hand, our attention turned to their biological activity. It was desired to further explore the growth defects which had been previously noted for natural products 1–4 against E. coli and S. aureus, and so

• replacement of the N-Me of 4 with the methylthiomethylene substituent of 7, nor epoxidation of 4’s side chain to give 8, offered any improvement in the biological activity. The result for 8 is particularly intriguing, as this natural product was noted to have the strongest effect upon the growth of H. pylori

Comparative cell biological study of in vitro antitumor and antimetastatic activity on melanoma cells of GnRH-III-containing conjugates modified with short-chain fatty acids

• Eszter Lajkó,
• Sarah Spring,
• Rózsa Hegedüs,
• Beáta Biri-Kovács,
• Sven Ingebrandt,
• Gábor Mező and
• László Kőhidai

Beilstein J. Org. Chem. 2018, 14, 2495–2509, doi:10.3762/bjoc.14.226

• GnRH-III(Dau=Aoa) (Figure 1) – were investigated in respect of their cell biological activity and their applicability for targeted melanoma therapy. The significance of the above-described modification in position 4 of GnRH-III was evaluated by characterization of the cellular uptake, the

Synergistic approach to polycycles through Suzuki–Miyaura cross coupling and metathesis as key steps

• Sambasivarao Kotha,
• Milind Meshram and
• Chandravathi Chakkapalli

Beilstein J. Org. Chem. 2018, 14, 2468–2481, doi:10.3762/bjoc.14.223

• -dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) to generate nitronaphthalene 15 (60%, Scheme 2). Due to their useful biological activity and intricate structural features of angucyclines such as 16–19 (Figure 2), several approaches have been reported for their assembly. In this context, de Koning and co

Investigation of the electrophilic reactivity of the biologically active marine sesquiterpenoid onchidal and model compounds

• Melissa M. Cadelis and
• Brent R. Copp

Beilstein J. Org. Chem. 2018, 14, 2229–2235, doi:10.3762/bjoc.14.197

• model protein lysozyme, forming covalent adducts and leading to protein cross-linking. These results provide preliminary evidence supporting the molecular mechanism of biological activity exhibited by onchidal. Keywords: dialdehyde; lysozyme; mollusc; onchidal; pyrrole; Introduction More than 80

• terpenoid natural products containing the 1,4-dialdehyde moiety have been isolated from sources such as fungi, algae, sponges and molluscs [1]. Many of these natural products exhibit biological activity, ranging from anti-inflammatory to antimicrobial and antifeedant activities [1]. The prototypical

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

• of palmarumycin CP1 were synthesized later which were showing good thioredoxin–thioredoxin reductase (Trx-1/TrxR) inhibitory activity [129]. It was observed that the introduction of enone functionality in naphthoquinone spiroketal enhances the biological activity of palmarumycin 138. Furthermore, Ley

Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates

• Yuichi Yoshimura,
• Hideaki Wakamatsu,
• Yoshihiro Natori,
• Yukako Saito and
• Noriaki Minakawa

Beilstein J. Org. Chem. 2018, 14, 1595–1618, doi:10.3762/bjoc.14.137

• unique biological activity of 4’-thionucleosides triggered the synthesis of their chalcogen isosters, 4’-selenonucleosides, the activity of which were reported. The first synthesis of 4’-selenonucleosides was reported by Jeong and co-workers in 2008 [48][49]. As in the case of the 4’-thioribonucleoside

Drug targeting to decrease cardiotoxicity – determination of the cytotoxic effect of GnRH-based conjugates containing doxorubicin, daunorubicin and methotrexate on human cardiomyocytes and endothelial cells

• Livia Polgár,
• Eszter Lajkó,
• Pál Soós,
• Orsolya Láng,
• Marilena Manea,
• Béla Merkely,
• Gábor Mező and
• László Kőhidai

Beilstein J. Org. Chem. 2018, 14, 1583–1594, doi:10.3762/bjoc.14.136

• showed no significant differences in the biological activity of Mtx isomers in conjugated form [24]. Fmoc-protected Dox was reacted with glutaric anhydride in DMF. The prepared Fmoc-Dox-14-O-hemiglutarate was used for conjugation using PyBOP in the presence of NMM, followed by the removal of Fmoc group

Novel unit B cryptophycin analogues as payloads for targeted therapy

• Eduard Figueras,
• Adina Borbély,
• Mohamed Ismail,
• Marcel Frese and
• Norbert Sewald

Beilstein J. Org. Chem. 2018, 14, 1281–1286, doi:10.3762/bjoc.14.109

• -52 and to better understand the fundamental structure for biological activity, numerous structure–activity relationship studies have been carried out [24][25][26][27][28][29][30][31][32][33][34][35]. However, like cryptophycin-52, the new analogues were not selective against cancer cells making them

• to investigate whether the high biological activity of the parent compound is retained and thus, construction of ADCs and PDCs would be feasible. This preparation could be done using traceless cleavable linkers that are sensitive to the distinct physiology of the tumour with enhanced level and

• column chromatography. The allyl ether in 23 was cleaved using Pd(PPh3)4 as Pd(0) source and phenylsilane as scavenger to obtain the cryptophycin analogue 24 in good purity. Biological evaluation The biological activity of the modified unit B analogues was determined in a cell viability assay using the

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• and in a number of other natural compounds that have shown a highly diverse range of biological activity [1][2][3][4][5][6][7][8][9], like the inhibitory activity of inositol monophosphatase [10][11], antitumor [12], antibiotic [12][13], and antibacterial activity [14] and lipoxygenase inhibitor

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

• -28). Both SST-14 and SST-28 exhibit biological activity through high-affinity membrane receptors (somatostatin receptor 1–5; SSTR1–5), that are widely distributed throughout the human body in various tissues like the nervous, pituitary, kidney, lung and immune cells [65][66]. SSTRs are overexpressed

• keeping only the peptide epitope responsible for the biological activity. The most widely known analogs of somatostatin are cyclic peptides named octreotide (d-Phe-c[Cys-Phe-d-Trp-Lys-Thr-Cys]-Thr-ol), lanreotide (d-2Nal-c[Cys-Tyr-d-Trp-Lys-Val-Cys]-Thr-NH2) and vapreotide (d-Phe-c[Cys-Tyr-d-Trp-Lys-Val

• intrinsic functional group for direct conjugation with the peptide/linker (Figure 4) or a functional group able to be derivatized for further conjugation (i.e., click chemistry [86]). In the latter case, the site of derivatization has to be carefully selected so that the biological activity of the drug and

Development of novel cyclic NGR peptide–daunomycin conjugates with dual targeting property

• Andrea Angelo Pierluigi Tripodi,
• Szilárd Tóth,
• Kata Nóra Enyedi,
• Gitta Schlosser,
• Gergely Szakács and
• Gábor Mező

Beilstein J. Org. Chem. 2018, 14, 911–918, doi:10.3762/bjoc.14.78

• CD13+ HT-1080 human fibrosarcoma and CD13− but integrin positive HT-29 human colon adenocarcinoma cells. However, it seems that the free ε-amino group of Lys in the cycle is not necessary for the biological activity. Therefore, we developed novel cyclic NGR peptide–daunomycin conjugates in which Lys

• characterization of novel cyclic NGR peptides and their corresponding NGR-drug conjugates. Special attention was paid on the chemostability and in vitro biological activity of the compounds [17][18]. Daunomycin (Dau) was used as cytotoxic agent, attached to the NGR-derivatives via oxime linkage. The prepared

• the use of orthogonal protecting groups (Figure 1A). Previous studies indicated that the free ε-amino group of Lys does not have an impact on the biological activity [15][17]. To prove our assumption, a set of novel cyclic NGR peptide–Dau conjugates were developed in which the Lys was replaced by