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

• byproducts – likely due to the poor reactivity of the substituted anilines as amino components of the Ugi-4CR. Nonetheless, the Passerini products were also evaluated and provided important information of the structure–activity relationship [24]. An additional library was built by performing the Ugi-4CR at a

New sesquiterpenoids from the South China Sea soft corals Clavularia viridis and Lemnalia flava

• Qihao Wu,
• Yuan Gao,
• Meng-Meng Zhang,
• Li Sheng,
• Jia Li,
• Xu-Wen Li,
• Hong Wang and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2019, 15, 695–702, doi:10.3762/bjoc.15.64

• 1, 2 and 4 exhibited considerable PTP1B inhibitory activity with IC50 values of 18.8, 21.8, and 15.6 μM, respectively. Compounds 1, 2 and 4 also showed strong NF-κB inhibitory activity with IC50 values of 19.9, 6.8 and 7.3 μM, respectively. With regard to their structure–activity relationship, the

Synthesis and SAR of the antistaphylococcal natural product nematophin from Xenorhabdus nematophila

• Frank Wesche,
• Hélène Adihou,
• Thomas A. Wichelhaus and
• Helge B. Bode

Beilstein J. Org. Chem. 2019, 15, 535–541, doi:10.3762/bjoc.15.47

• Frankfurt, Max-von-Laue-Str. 15, D-60438 Frankfurt am Main, Germany 10.3762/bjoc.15.47 Abstract The repeated and improper use of antibiotics had led to an increased number of multiresistant bacteria. Therefore, new lead structures are needed. Here, the synthesis and an expanded structure–activity

• relationship of the simple and antistaphylococcal amide nematophin from Xenorhabdus nematophila and synthetic derivatives are described. Moreover, the synthesis of intrinsic fluorescent derivatives, incorporating azaindole moieties was achieved for the first time. Keywords: azaindole; fluorescent dye; MRSA

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

• . The present studies gave some information of which structural units are required for the toxic activity, but are not sufficient. Further investigations are necessary to address the structure–activity relationship. Experimental General analytical methods NMR spectra were recorded in acetone-d6 on a

The influence of the cationic carbenes on the initiation kinetics of ruthenium-based metathesis catalysts; a DFT study

• Magdalena Jawiczuk,
• Angelika Janaszkiewicz and
• Bartosz Trzaskowski

Beilstein J. Org. Chem. 2018, 14, 2872–2880, doi:10.3762/bjoc.14.266

• catalysts synthesized up to date the rational design of new catalysts remains a non-trivial task. To gain general insight into the structure–activity relationship for this class of compounds we computationally investigated three different carbenes bearing a formal +1 charge, in form of quaternary amine, and

Pd-Catalyzed microwave-assisted synthesis of phosphonated 13α-estrones as potential OATP2B1, 17β-HSD1 and/or STS inhibitors

• Rebeka Jójárt,
• Szabolcs Pécsy,
• György Keglevich,
• Mihály Szécsi,
• Réka Rigó,
• Csilla Özvegy-Laczka,
• Gábor Kecskeméti and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 2838–2845, doi:10.3762/bjoc.14.262

• the test compounds inhibited the STS markedly. The structure–activity relationship evaluation revealed that 2-substituted 3-hydroxy derivatives are able to inhibit the 17β-HSD1 enzyme with submicromolar IC50 values. Dual OATP2B1 and 17β-HSD1 inhibitors have been identified. Keywords: catalysis

Synthesis of pyrrolidine-based hamamelitannin analogues as quorum sensing inhibitors in Staphylococcus aureus

• Jakob Bouton,
• Kristof Van Hecke,
• Reuven Rasooly and
• Serge Van Calenbergh

Beilstein J. Org. Chem. 2018, 14, 2822–2828, doi:10.3762/bjoc.14.260

• further elucidate the structure–activity relationship. The pyrrolidine nitrogen atom provides an extra point of diversification, allowing further elaboration of the scaffold. Substituents on the ring nitrogen might lead to additional interactions with the target and therefore provide more potent analogues

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

• , traditionally considered to be challenging scaffolds. Screening of the library provided valuable insights into the structure–activity relationship of the bacterial growth defects, and suggested that selectivity between bacterial species should be attainable. Furthermore, a structurally related series of

Microwave-assisted synthesis of biologically relevant steroidal 17-exo-pyrazol-5'-ones from a norpregnene precursor by a side-chain elongation/heterocyclization sequence

• Gergő Mótyán,
• László Mérai,
• Márton Attila Kiss,
• Zsuzsanna Schelz,
• Izabella Sinka,
• István Zupkó and
• Éva Frank

Beilstein J. Org. Chem. 2018, 14, 2589–2596, doi:10.3762/bjoc.14.236

• hormones, and therefore, in the development of prostate cancer [1]. According to extensive structure–activity relationship and docking studies, a potent steroidal inhibitor should possess certain structural characteristics for efficient P45017α inhibition [1][2][3], such as (i) a five or six-membered non

Quinolines from the cyclocondensation of isatoic anhydride with ethyl acetoacetate: preparation of ethyl 4-hydroxy-2-methylquinoline-3-carboxylate and derivatives

• Nicholas G. Jentsch,
• Jared D. Hume,
• Emily B. Crull,
• Samer M. Beauti,
• Amy H. Pham,
• Julie A. Pigza,
• Jacques J. Kessl and
• Matthew G. Donahue

Beilstein J. Org. Chem. 2018, 14, 2529–2536, doi:10.3762/bjoc.14.229

• . Structure–activity relationship studies have indicated that the 2-methyl and 3-acetic acid residues are crucial to maintaining the potency of this scaffold [10]. The Boehringer Ingelheim chemical development route toward the synthesis of quinoline 1 is shown in Scheme 1 [11]. The northern tricyclic

Synthesis of a leopolic acid-inspired tetramic acid with antimicrobial activity against multidrug-resistant bacteria

• Luce Mattio,
• Loana Musso,
• Leonardo Scaglioni,
• Andrea Pinto,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2018, 14, 2482–2487, doi:10.3762/bjoc.14.224

• with an increased activity due to the presence of the tetramic acid core. In this paper we report the efforts made to develop a synthetic strategy to compound 1, which may, in principle, have a value in the preparation of various analogues for structure–activity relationship (SAR) studies. The

• considered as a promising candidate for further investigation. Efforts to synthesize analogues of compound 1 to deepen the structure–activity relationship (SAR) study of this novel class of antibacterial agents are underway. Structures of leopolic acid A and compound 1. Synthesis of 3-decyltetramic

Efficient catalytic alkyne metathesis with a fluoroalkoxy-supported ditungsten(III) complex

• Henrike Ehrhorn,
• Janin Schlösser,
• Dirk Bockfeld and
• Matthias Tamm

Beilstein J. Org. Chem. 2018, 14, 2425–2434, doi:10.3762/bjoc.14.220

• fluoroalkoxide ligands [55][56][57]. The difference in the optimum degree of fluorination for molybdenum and tungsten is rationalized by the increased intrinsic electrophilicity of tungsten compared to molybdenum [56]. Based on these insights into the structure–activity relationship of alkyne metathesis

Defining the hydrophobic interactions that drive competence stimulating peptide (CSP)-ComD binding in Streptococcus pneumoniae

• Bimal Koirala,
• Robert A. Hillman,
• Erin K. Tiwold,
• Michael A. Bertucci and
• Yftah Tal-Gan

Beilstein J. Org. Chem. 2018, 14, 1769–1777, doi:10.3762/bjoc.14.151

• , suggesting that these residues are involved in receptor binding and specificity [29]. Previously, Yang et al. conducted a systematic structure–activity relationship (SAR) analysis of the CSP1 scaffold and found that the hydrophobic residues in positions 4, 7, 8, 11, 12 and 13, along with Arg3, are important

Natural and redesigned wasp venom peptides with selective antitumoral activity

• Marcelo D. T. Torres,
• Gislaine P. Andrade,
• Roseli H. Sato,
• Cibele N. Pedron,
• Tania M. Manieri,
• Giselle Cerchiaro,
• Anderson O. Ribeiro,
• Cesar de la Fuente-Nunez and
• Vani X. Oliveira Jr.

Beilstein J. Org. Chem. 2018, 14, 1693–1703, doi:10.3762/bjoc.14.144

• cancer cells, which are zwitterionic and negatively charged, respectively. Structure–activity relationship studies have identified amphiphilicity and polar angle as the most important physicochemical properties required for ACPs to invade cancer cells or disturb their membranes [22][23]. In 2007, Konno

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

• 15 conjugates are also demonstrated in the most important two targets of cardiac tissue (myocytes and endothelium). Data presented in Table 1 provide a good basis for structure–activity relationship analysis of the reported results. Comparison of IC50 values of conjugates possessing no cardiotoxicity

Enantioselective phase-transfer catalyzed alkylation of 1-methyl-7-methoxy-2-tetralone: an effective route to dezocine

• Ruipeng Li,
• Zhenren Liu,
• Liang Chen,
• Jing Pan and
• Weicheng Zhou

Beilstein J. Org. Chem. 2018, 14, 1421–1427, doi:10.3762/bjoc.14.119

• . (Some reports on the non-stereoselective alkylation of 2 were given in references [11][12]). In this paper, several cinchona-derived phase-transfer catalysts were screened for this reaction, and the structure–activity relationship for the catalysis was studied. In addition, optimizations had been made

• ). Subsequently, when the groups substituted at the para-position on the benzyl group were investigated, the structure–activity relationship showed that catalyst C4 (with methyl substituent) did not work for the reaction (Table 1, entry 4) and those with Cl or F (C5 and C6) worked well with an improvement in

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

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• structure–activity relationship. It has been observed that the number and position of pyrrole rings are crucial for antileukemic activity. The presence of pyrrole rings close to the alkylating BAM moiety is responsible for better cytotoxic activity both in vitro and in vivo, whereas a pyrazole ring in close

A stereoselective and flexible synthesis to access both enantiomers of N-acetylgalactosamine and peracetylated N-acetylidosamine

• Bettina Riedl and
• Walther Schmid

Beilstein J. Org. Chem. 2018, 14, 856–860, doi:10.3762/bjoc.14.71

• . In contrast to the thoroughly investigated properties of GalNAc, other stereoisomers have not been probed for biological or pharmaceutical activity, yet. Highly flexible synthetic routes are required to access and probe the entire compound class of 2-amino-2-deoxysugars for further structure–activity

• relationship studies. Several strategies for the synthesis of 2-amino sugars have been published so far. In one exemplary straightforward approach, GalNAc was prepared by inverting the stereogenic center at the C-4 position of N-acetylglucosamine (GlcNAc) [10]. However, the necessity of using a 2-amino sugar

Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

• Kartik Temburnikar and
• Katherine L. Seley-Radtke

Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65

• ), respiratory syncytial virus (RSV, Pneumoviridae) and the hepatitis-C virus (HCV, Flaviviridae) family [63][65][69]. Through structure activity relationship studies, the 1'-CN compound 4 emerged as a compound with activity against EBOV, HCV and RSV [65][69]. It is active against EBOV in human microvascular

• for structure–activity relationship [71][72]. Synthesis of 1',2'-cyclopentyl C-nucleoside [73]. Functional groups at C1' and C2' were installed and employed for ring cyclization. Anti-influenza C-nucleosides mimicking favipiravir riboside [74]. A. Structure of favipiravir and its riboside, which

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

• LPS isolates from wild-type or laboratory-adapted Gram-negative bacteria, the clinical and cellular studies as well as structure–activity relationship investigations using native LPS are complicated and difficult to evaluate. The lipid A content of LPS generally comprises a complex mixture of

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

• structure and fascinating biology, mycolactones have inspired various total synthesis endeavors and structure–activity relationship studies. Although this review intends to cover all synthesis efforts in the field, special emphasis is given to the comparison of conceptually different approaches and to the

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

• Adam and Eve that automate drug development via cycles of quantitative structure–activity relationship (QSAR) learning and biological testing (Figure 3) [16][17][18]. Eve’s selection of compounds was more cost efficient than standard drug screening, and the robotic scientist has identified several new

Structure–efficiency relationships of cyclodextrin scavengers in the hydrolytic degradation of organophosphorus compounds

• Sophie Letort,
• Michaël Bosco,
• Benedetta Cornelio,
• Frédérique Brégier,
• Sébastien Daulon,
• Géraldine Gouhier and
• François Estour

Beilstein J. Org. Chem. 2017, 13, 417–427, doi:10.3762/bjoc.13.45

• iodosobenzoate group and the methylated oligosaccharide; (4) in case of soman, the degradation is enhanced by a cooperative effect observed between the imidazole and 2-iodosobenzoate when the latter is in close proximity to the macrocycle. A more extended structure–activity relationship study is envisaged to

Posttranslational isoprenylation of tryptophan in bacteria

• Masahiro Okada,
• Tomotoshi Sugita and
• Ikuro Abe

Beilstein J. Org. Chem. 2017, 13, 338–346, doi:10.3762/bjoc.13.37

• -terminal cysteine (Figure 1B) [9][10]. Each pheromone causes the opposite type of cell to induce the reciprocal conjugation of the heterothallic cells, through the formation of a conjugation tube for mating. A structure–activity relationship study on tremerogen A-10 demonstrated that both the amino acid

• responses in B. subtilis and related bacilli [3]. Structure–activity relationship studies on the ComXRO-E-2 pheromone derived from Bacillus strain RO-E-2, which is a hexapeptide with a geranyl-modified tryptophan residue, revealed that the exact chemical structure of the geranyl group and the absolute