Fluorinated azobenzenes as supramolecular halogen-bonding building blocks

• Esther Nieland,
• Oliver Weingart and
• Bernd M. Schmidt

Beilstein J. Org. Chem. 2019, 15, 2013–2019, doi:10.3762/bjoc.15.197

• reaction and as organocatalysts in Diels–Alder reactions [27]. The group of Metrangolo also reported halogen bonding-promoted catalysis in water by exploiting a halogen bonding amino acid, which combines excellent donor properties with good water solubility [28], in addition to their seminal contributions

Archangelolide: A sesquiterpene lactone with immunobiological potential from Laserpitium archangelica

• Silvie Rimpelová,
• Michal Jurášek,
• Lucie Peterková,
• Jiří Bejček,
• Vojtěch Spiwok,
• Miloš Majdl,
• Michal Jirásko,
• Miloš Buděšínský,
• Juraj Harmatha,
• Eva Kmoníčková,
• Pavel Drašar and
• Tomáš Ruml

Beilstein J. Org. Chem. 2019, 15, 1933–1944, doi:10.3762/bjoc.15.189

• ). The first round of simulations (1–10 ns) of compound 1 docking into SERCA cavity with compound 1 constrained as described (simulation 1) showed the presence of hydrophobic interactions of ligand side chains with Phe256, Val263, Ile829 and the hydrophobic part of Gln259 amino acid residues. Gln259 was

• -specific dye from [20] (10 min; image C) or pDNA coding mCherry-ER (image G). D, H) merged images. Cartoon representation of sarco/endoplasmic reticulum Ca2+ ATPase binding pocket with A, C) archangelolide (1) or B, D) trilobolide (2) after molecular dynamic simulations. Depicted are also amino acid

Complexation of chiral amines by resorcin[4]arene sulfonic acids in polar media – circular dichroism and diffusion studies of chirality transfer and solvent dependence

• Bartosz Setner and
• Agnieszka Szumna

Beilstein J. Org. Chem. 2019, 15, 1913–1924, doi:10.3762/bjoc.15.187

• chemistry. In the present study we demonstrate that resorcin[4]arene sulfonic acid (RSA) interacts with chiral amines (amino acid derivatives and aminocavitands) to form inclusion complexes and capsules based on electrostatic interactions. The complexes were characterized by circular dichroism and DOSY NMR

• procedure described in the literature [16]. Complexes of 1 with various amino acid methyl esters (LysOMe·2HCl, ArgOMe·2HCl, HisOMe·2HCl) and with (R or S)-2·4HCl were obtained by dissolution of the components in water (or in water with sodium acetate buffer, pH 7.0) and mixing the solutions in 1:1 (for

• informative and reflect the thermodynamic stability of complexes. They also suggest that this technique may be suitable for estimation of the order of thermodynamic stability of the complexes using only a single-spectrum measurement. Assuming that the size of amino acid derivatives is roughly similar and

Installation of -SO₂F groups onto primary amides

• Jing Liu,
• Shi-Meng Wang,
• Njud S. Alharbi and
• Hua-Li Qin

Beilstein J. Org. Chem. 2019, 15, 1907–1912, doi:10.3762/bjoc.15.186

• ][15][16][17][18][19]. Among all the developed S(VI)–F species, sulfonyl fluoride (RSO2F) was specifically recognized as unique scaffold for covalent protein inhibitors and biological probes with the affinity-driven activation for forming covalent linkages with the amino acid residues of protein

Design, synthesis and biological evaluation of immunostimulating mannosylated desmuramyl peptides

• Rosana Ribić,
• Ranko Stojković,
• Lidija Milković,
• Mariastefania Antica,
• Marko Cigler and
• Srđanka Tomić

Beilstein J. Org. Chem. 2019, 15, 1805–1814, doi:10.3762/bjoc.15.174

• -isoGln pharmacophore is essential for the immunostimulatory properties but the introduction of lipophilic substituent into MDP analogues can increase its adjuvant activity [12][18]. Up to now, our research was directed towards isomeric desmuramyl peptides containing lipophilic unnatural amino acid

• racemic Boc-protected (adamant-1-yl)glycine [32] 2 using the carbodiimide EDC/HOBt method [21]. The obtained mixture of BocAdGly-ʟ-Ala-ᴅ-isoGlnOBn diastereoisomers was treated with trifluoroacetic acid in order to remove the Boc protecting group while the diastereoisomer 4 with ᴅ-ʟ-ᴅ amino acid sequence

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• can serve as the starting material to a variety of orthogonally protected derivatives of 2,3-diaminopropanoic acid. The bicyclic amino acid (S)-127 is a major metabolite of isazofos in corn grain and for toxicological studies both enantiomers were required [17]. To this end the aziridine ester (2S,1′R

• presence of acetic anhydride produced a crude acetamido ester (R)-132 which was transformed into the final N-benzyl amide (R)-130 with of 99.9% ee after crystallization. ʟ-(+)-Furanomycin (Scheme 35) is a natural nonproteinogenic amino acid which showed pronounced antibacterial activity. From several

• allyl ether (2R,1'R,1''R)-135 which in the presence of Grubbs 1st generation catalyst produced (2R,1'R,1''R)-136. Transformation of the aziridine portion of 136 into an amino acid fragment of norfuranomycin (2S,2'R)-133 was accomplished starting from the hydrolytic opening of the aziridine ring and was

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

• , perhaps because the α,β-unsaturated double bond affected the iodination. Mohan et al. successfully developed an efficient copper-catalyzed aerobic oxidative amination of C(sp3)–H bonds to synthesize imidazo[1,5-a]pyridine derivatives [122]. The reaction was also applicable to amino acid derivatives, as

Synthesis and conformational preferences of short analogues of antifreeze glycopeptides (AFGP)

• Małgorzata Urbańczyk,
• Michał Jewgiński,
• Joanna Krzciuk-Gula,
• Jerzy Góra,
• Rafał Latajka and
• Norbert Sewald

Beilstein J. Org. Chem. 2019, 15, 1581–1591, doi:10.3762/bjoc.15.162

• conformation of the molecule as well an on the stereochemistry of amino acid residues. The desired monoglycosylated analogues with acetylated amino termini and the carboxy termini in form of N-methylamide have been synthesized. Conformational nuclear magnetic resonance (NMR) studies of the designed analogues

• have shown a strong influence of the stereochemistry of amino acid residues on the peptide chain stability, which could be connected to the antifreeze activity of these compounds. A better understanding of the mechanism of action of antifreeze glycopeptides would allow applying these materials, e.g

• the saccharide moiety is conformationally well-defined by the peptide backbone and the whole structure adopts a polyproline II (PP II) helix [17]. Antifreeze activity strongly relies on the stereochemistry of the amino acid residues. Earlier studies have shown that AFGP analogues containing either an

Molecular basis for the plasticity of aromatic prenyltransferases in hapalindole biosynthesis

• Takayoshi Awakawa and
• Ikuro Abe

Beilstein J. Org. Chem. 2019, 15, 1545–1551, doi:10.3762/bjoc.15.157

• prenyl donor [12]. This plasticity is due to the hydrophobic nature of the prenyl acceptor binding site and the fluctuations of the amino acids forming the cation shield, similarly to AmbP3. Comparison of the AmbP1 and AmbP3 amino acid sequences with other ABBA PTases The AmbP1 and AmbP3 amino acid

• amino acid sequence alignment of AmbP1, AmbP3, and other ABBA PTases, visualized by ESPript3 [34]. Secondary structure elements: α, α-helices; β, β-strands; η, 310-helices; TT, strict β-turns. The red frames indicate amino acids that anchor pyrophosphate, the blue frames indicate the residues that

An azobenzene container showing a definite folding – synthesis and structural investigation

• Abdulselam Adam,
• Saber Mehrparvar and
• Gebhard Haberhauer

Beilstein J. Org. Chem. 2019, 15, 1534–1544, doi:10.3762/bjoc.15.156

• for such rigid systems are macrocycles which stem from Lissoclinum cyclopeptide alkaloids (Figure 1) [2][3]. Here, the required recognition units can be introduced via the amino acid side chains or via the side chains of the azole rings. The orientation and the distance between the recognition units

• are determined by the type and size of the macrocyclic platform, e.g., if all of the amino acid side chains are of the same configuration, they are presented on one face of the macrocycle in a convergent manner. The artificial Lissoclinum cyclopeptide platforms feature C2, C3 and C4 symmetry [3]. So

• the amino acid side chains, are described in the literature [49][50]. One example is the platform 4, which consists of two imidazole building blocks connected by two azobenzene units (Figure 2) [50]. Irradiation of the platform 4 with UV light results in a trans→cis isomerization accompanied by a

Anomeric sugar boronic acid analogues as potential agents for boron neutron capture therapy

• Daniela Imperio,
• Erika Del Grosso,
• Silvia Fallarini,
• Grazia Lombardi and
• Luigi Panza

Beilstein J. Org. Chem. 2019, 15, 1355–1359, doi:10.3762/bjoc.15.135

• . Galactose and fructose also allow tumor growth in the absence of glucose. Boronic acid derivatives have gained interest in the last years in different fields such as the development of enzyme inhibitors, drug delivery polymers, saccharide sensors and as boron carriers for BNCT, e.g., amino acid derivatives

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

• -lactam, albeit functionalized in the side chain. The one-pot synthesis of the β-lactam steroid was achieved via the Ugi 3-component-4-center reaction using the dehydrocholic aldehyde 1 as carbonyl component. This variation of the Ugi reaction including a β-amino acid component allows the formation of the

• paraformaldehyde and benzyl isocyanide to form hybrid 11 in good yield. Similarly, the spirostanic lactone 12 was transformed into spirostanic acid 13 and amine 14, which were next ligated to alanine methyl ester and Boc-histidine leading to the amino acid–steroid conjugates 15 and 16, respectively. This approach

• was also employed for the ligation of amino acids to spirostanic seco-steroids at ring B and for the simultaneous incorporation of two amino acid residues [19]. Ramírez and co-workers have extended the application of the Ugi-4CR to the diversity-oriented functionalization of androstanic and preganinc

Ugi reaction-derived prolyl peptide catalysts grafted on the renewable polymer polyfurfuryl alcohol for applications in heterogeneous enamine catalysis

• Alexander F. de la Torre,
• Gabriel S. Scatena,
• Oscar Valdés,
• Daniel G. Rivera and
• Márcio W. Paixão

Beilstein J. Org. Chem. 2019, 15, 1210–1216, doi:10.3762/bjoc.15.118

• system producing γ-nitroaldehyde 5 with PFA-supported catalyst 3 packed in a microreactor. Schematic synthesis of polyfurfulyl alcohol (PFA) incorporating a prolyl peptide catalyst. AA: Amino acid. Utilization of the Ugi four-component reaction (Ugi-4CR) for the synthesis of prolyl pseudo-peptide

Phylogenomic analyses and distribution of terpene synthases among Streptomyces

• Lara Martín-Sánchez,
• Kumar Saurabh Singh,
• Mariana Avalos,
• Gilles P. van Wezel,
• Jeroen S. Dickschat and
• Paolina Garbeva

Beilstein J. Org. Chem. 2019, 15, 1181–1193, doi:10.3762/bjoc.15.115

• genus Streptomyces. However, if bacteria from other taxonomic groups such as myxobacteria and cyanobacteria and their geosmin synthases are included in a phylogenetic analysis, it can be seen that the geosmin synthase amino acid sequences from distantly related organisms clearly fall into distant clades

Stereo- and regioselective hydroboration of 1-exo-methylene pyranoses: discovery of aryltriazolylmethyl C-galactopyranosides as selective galectin-1 inhibitors

• Alexander Dahlqvist,
• Axel Furevi,
• Niklas Warlin,
• Hakon Leffler and
• Ulf J. Nilsson

Beilstein J. Org. Chem. 2019, 15, 1046–1060, doi:10.3762/bjoc.15.102

• ; galectin-1; hydroboration; inhibition; selective; triazole; Introduction Galectins are defined by a typically about 130 amino acid carbohydrate recognition domain (CRD) that binds to carbohydrates with at least one β-galactose subunit within a binding pocket large enough to accommodate a tetrasaccharide

Mechanistic investigations on multiproduct β-himachalene synthase from Cryptosporangium arvum

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 1008–1019, doi:10.3762/bjoc.15.99

• -himachalene synthase produces numerous side products Apart from the recently assigned (Z)-γ-bisabolene synthase (BbS) [13], the soil-dwelling actinomycete Cryptosporangium arvum DSM 44712 also possesses a second TS gene (accession no. WP_035852539). Its encoded amino acid sequence (Figure S1, Supporting

• expression, protein purification, incubation experiments with isotopically labelled precursors, preparative scale incubation and synthesis of (2-13C)DMAPP. The amino acid sequence of HcS, a phylogenetic tree of bacterial terpene synthases, SDS-PAGE analysis of the recombinant protein, listed NMR data for 1

Heck- and Suzuki-coupling approaches to novel hydroquinone inhibitors of calcium ATPase

• Robert J. Kempton,
• Taylor A. Kidd-Kautz,
• Soizic Laurenceau and
• Stefan Paula

Beilstein J. Org. Chem. 2019, 15, 971–975, doi:10.3762/bjoc.15.94

• convey specificity for prostate cancer cells. Keywords: calcium ATPase inhibitors; Heck- and Suzuki-coupling reactions; hydroquinones; prostate cancer; tethered amino acid; Introduction Sarco/endoplasmic reticulum calcium ATPase (SERCA) is an integral protein that resides in the membrane of the

Synthesis of (macro)heterocycles by consecutive/repetitive isocyanide-based multicomponent reactions

• Angélica de Fátima S. Barreto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2019, 15, 906–930, doi:10.3762/bjoc.15.88

• isocyanides to obtain six tetrazole peptidomimetics (20a–f). Highly complex molecules were easily obtained in only two steps (sequential Ugi-tetrazole/Ugi-reaction) without the need for amino acid protection/deprotection reactions. A remarkable result was described by Orru and co-workers who used two

• method for the synthesis of macroheterocycles, which could be easily accomplished in a reduced number of steps and very short reaction periods (except for the last step). Three consecutive Ugi reactions were performed followed by the respective hydrolysis and deprotection, furnishing an amino acid, which

• bidirectional macrocycles with exocyclic substituents with side chains derived from natural products [47]. The combination of acid components with side chains derived from natural products containing amino acid residues (e.g., Arg, Cys, His, Trp) and sugar, bifunctional components (diamino/diisocyanide) and

Synthesis of a novel category of pseudo-peptides using an Ugi three-component reaction of levulinic acid as bifunctional substrate, amines, and amino acid-based isocyanides

• Maryam Khalesi,
• Azim Ziyaei Halimehjani and
• Jürgen Martens

Beilstein J. Org. Chem. 2019, 15, 852–857, doi:10.3762/bjoc.15.82

• synthesis of a novel category of pseudo-peptides via intramolecular Ugi reaction of levulinic acid (4-oxopentanoic acid), aromatic and aliphatic amines, and amino acid-based isocyanides is reported. Levulinic acid was applied as a bifunctional substrate containing both carbonyl and acid moieties suitable

• for the Ugi reaction. This article provides a facile and convenient one-pot procedure for the synthesis of peptide-like heterocyclic molecules containing 2-pyrrolidone (γ-lactam), amide and ester functional groups with good to excellent yields. Keywords: amino acid-based isocyanides; levulinic acid

• acid, aromatic and aliphatic amines and amino acid-based isocyanides. First of all, racemic α-amino acids such as DL-tryptophan, DL-phenylalanine and DL-leucine were used as amine source for the synthesis of isocyanide esters 3 through three sequential reactions [30][31]. The first reaction is

Synthesis of acylglycerol derivatives by mechanochemistry

• Karen J. Ardila-Fierro,
• Andrij Pich,
• Marc Spehr,
• José G. Hernández and
• Carsten Bolm

Beilstein J. Org. Chem. 2019, 15, 811–817, doi:10.3762/bjoc.15.78

• loads has led to mechanoenzymatic transformations [5][6][7], and to synthesize amino acid derivatives [8][9][10] and peptides [11][12][13] by ball milling and extrusion techniques. Similarly, mechanochemical derivatizations of sugars and sugar derivatives such as cyclodextrins (CDs) have proven

Stereochemical investigations on the biosynthesis of achiral (Z)-γ-bisabolene in Cryptosporangium arvum

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 789–794, doi:10.3762/bjoc.15.75

• the soil actinomycete Cryptosporangium arvum DSM 44712 was cloned into the E. coli expression vector pYE-express [13] (Table S1, Supporting Information File 1), because of its phylogenetic distance to characterised TSs (Figure S1, Supporting Information File 1). The amino acid sequence of the enzyme

• origin in FPP. Supporting Information Experimental details of culture conditions, gene cloning, protein purification, incubation experiments, isolation of 5 and HPLC purifications, the amino acid sequence of BbS, a phylogenetic tree with the location of BbS, SDS-PAGE analysis, listed NMR data of 5

Solid-phase synthesis of biaryl bicyclic peptides containing a 3-aryltyrosine or a 4-arylphenylalanine moiety

• Iteng Ng-Choi,
• Àngel Oliveras,
• Lidia Feliu and
• Marta Planas

Beilstein J. Org. Chem. 2019, 15, 761–768, doi:10.3762/bjoc.15.72

• peptidyl resin precursor containing the required boronate and halogenated amino acid derivatives followed by its cyclization through the formation of an aryl–aryl bond between these two amino acids via a Suzuky–Miyaura reaction. It is worthwhile to mention that both the borylation and the cross-coupling

Synthesis of the polyketide section of seragamide A and related cyclodepsipeptides via Negishi cross coupling

• Jan Hendrik Lang and
• Thomas Lindel

Beilstein J. Org. Chem. 2019, 15, 577–583, doi:10.3762/bjoc.15.53

• , whereas the use of exactly stoichiometric amounts resulted in incomplete N-methylation. Treating the Boc-protected methyl ester of iodotyrosine 21 with a larger excess of base and methyl iodide (10 equiv each) led to the formation of the α-quaternary amino acid 23 (Scheme 4). An alternative route to the N

• -methylated product via oxazolidinone 24 was hampered by low yield on reaction with paraformaldehyde [47][48]. Although subsequent reduction of 24 with Et3SiH/TFA and reprotection of the free N-methyl amino acid with Boc2O proceeded smoothly and delivered iodotyrosine 25, the overall yield via 24 was not

• recent synthesis of plusbacin A3, Ichikawa et al. experienced similar difficulties when attempting esterification of a bulky β-OTIPS-substituted amino acid with a secondary alcohol under a variety of conditions [49]. Conclusion We developed a short synthesis of the polyketide building block present in

Dirhodium(II)-catalyzed [3 + 2] cycloaddition of N-arylaminocyclopropane with alkyne derivatives

• Wentong Liu,
• Yi Kuang,
• Zhifan Wang,
• Jin Zhu and
• Yuanhua Wang

Beilstein J. Org. Chem. 2019, 15, 542–550, doi:10.3762/bjoc.15.48

• no cis product formed. After further removal of the para-methoxyphenyl (PMP) group using ammonium cerium nitrate (CAN), the cyclic β-amino acid ester 5b was obtained with a yield of 80%. Cyclic β-amino acids and derivatives have good bioactivity and are widely used as key synthetic intermediates in

• method has potential synthetic practicality by providing a convenient way to synthesize trans-cyclic β-amino acid derivatives. Further application of this method with other cycloaddition partners and asymmetric synthesis of the chiral ring with the help of chiral auxiliaries are currently underway

Design of indole- and MCR-based macrocycles as p53-MDM2 antagonists

• Constantinos G. Neochoritis,
• Maryam Kazemi Miraki,
• Eman M. M. Abdelraheem,
• Ewa Surmiak,
• Tryfon Zarganes-Tzitzikas,
• Beata Łabuzek,
• Tad A. Holak and
• Alexander Dömling

Beilstein J. Org. Chem. 2019, 15, 513–520, doi:10.3762/bjoc.15.45

• optimization, we improved the Ugi-macrocyclization procedure compared to our previous findings utilizing microwave irradiation (see Supporting Information File 1); Firstly, the corresponding amino acid was irradiated with indole-3-carboxaldehyde derivatives 6 using MeOH as solvent (5 mL) at 120 °C for 1 h