Synthesis and in vitro biochemical evaluation of oxime bond-linked daunorubicin–GnRH-III conjugates developed for targeted drug delivery

• Sabine Schuster,
• Beáta Biri-Kovács,
• Bálint Szeder,
• Viktor Farkas,
• László Buday,
• Zsuzsanna Szabó,
• Gábor Halmos and
• Gábor Mező

Beilstein J. Org. Chem. 2018, 14, 756–771, doi:10.3762/bjoc.14.64

• macromolecules such as mRNA and DNA [10][11]. More precisely, anthracyclines act as topoisomerase II toxins inhibiting DNA transcription and replication. They stabilize a DNA topoisomerase-II intermediate in which the DNA strands are separated and a specific tyrosine residue of the topoisomerase II is covalently

• linked to the DNA by formation of a tyrosine phosphodiester [10][11][12]. Moreover, anthracyclines provide a beneficial auto-fluorescence allowing the performance of fluorescence based studies like confocal laser scanning microscopy (CLSM) and fluorescence-activated cell sorting (FACS) to investigate the

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• such intermediates. By selecting the appropriate reaction conditions (various pH and temperatures), they were able to alkylate free amino acids, e.g., glycine (Gly), L-serine (Ser), L-cysteine (Cys), L-lysine (Lys), L-tyrosine (Tyr) and glutathione (Glu) in aqueous solution to isolate 55 (Scheme 8

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• effects is associated with pyrazolo[3,4-d]pyrimidines. They are known to exhibit antiviral [111][112], pesticidal [113], anti-inflammatory [114], antimicrobial [115][116][117], antileukemic [118], antitumor [114][119][120], pan-RAF inhibiting [121], tyrosine kinase RET inhibiting [122], CNS [123

Position-dependent impact of hexafluoroleucine and trifluoroisoleucine on protease digestion

• Susanne Huhmann,
• Anne-Katrin Stegemann,
• Kristin Folmert,
• Damian Klemczak,
• Johann Moschner,
• Michelle Kube and
• Beate Koksch

Beilstein J. Org. Chem. 2017, 13, 2869–2882, doi:10.3762/bjoc.13.279

• assay [30]. Substitution of tryptophan, tyrosine, and phenylalanine residues in a glycosylation-deficient mutant of Candida antarctica lipase B, CalB N74D, by their monofluorinated analogues, left the resistance to proteolytic degradation by proteinase K unchanged [31]. Incorporation of α-fluoroalkyl

• phenylalanine, tyrosine, tryptophan, and leucine in the P1 position. Secondary hydrolysis also occurs at the carbonyl end of isoleucine, methionine, serine, threonine, valine, histidine, glycine, and alanine [47][58][59][60]. The S2 subsite of α-chymotrypsin generally prefers to accommodate hydrophobic residues

Asymmetric synthesis of propargylamines as amino acid surrogates in peptidomimetics

• Matthias Wünsch,
• David Schröder,
• Tanja Fröhr,
• Lisa Teichmann,
• Sebastian Hedwig,
• Nils Janson,
• Clara Belu,
• Jasmin Simon,
• Shari Heidemeyer,
• Philipp Holtkamp,
• Jens Rudlof,
• Lennard Klemme,
• Alessa Hinzmann,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2017, 13, 2428–2441, doi:10.3762/bjoc.13.240

• , phenylglycine and tyrosine) have been prepared using a large excess (4 equivalents) of [(trimethylsilyl)ethynyl]dimethylaluminum as the nucleophile [14][48][52]. The reaction of the sulfinylimines 5 with (trimethylsilyl)ethynyllithium provided the crude intermediates 6, which were converted into the N-sulfinyl

• % [21]. Synthesis of propargylamines containing electron-withdrawing substituents Aromatic and carbonyl substituents in the Cβ-position of propargylamines (occurring in analogoues of the amino acids phenylalanine, tyrosine, histidine, tryptophan, aspartic acid and asparagine) increase the acidity of the

• imine 5h) after desilylation with TBAF (Table 2). As the benzylic proton of sulfinylimine 5h is quite acidic, approach II was not pursued for the synthesis of propargylamines analogous to tyrosine, histidine, tryptophan, and aspartate. Proteinogenic amino acids do not contain substituents, which

Phosphonic acid: preparation and applications

• Charlotte M. Sevrain,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2017, 13, 2186–2213, doi:10.3762/bjoc.13.219

• applications in biology and medicine to mimic the phosphate group leading to antiretroviral drugs (e.g., tenofovir (1)) [39], isoprenoid biosynthesis inhibitors [40][41], antibiotics (e.g., fosfomycin (2)) [42], tyrosine phosphatase inhibitors 3 [43], antimalarial 4 [44], antihypertensive drugs (e.g., K4 5 and

• -butyl phosphonate was used for the synthesis of phosphonic acid analogues of peptides like protein-tyrosine kynases (PTKs) [134] or to prepare gadolinium complexes used as magnetic resonance imaging (MRI) contrast agents [135][136]. The introduction of the di-tert-butyl phosphonate was achieved by the

Oxidative dehydrogenation of C–C and C–N bonds: A convenient approach to access diverse (dihydro)heteroaromatic compounds

• Santanu Hati,
• Ulrike Holzgrabe and
• Subhabrata Sen

Beilstein J. Org. Chem. 2017, 13, 1670–1692, doi:10.3762/bjoc.13.162

• alkaloids such as luotonin A, tryptanthrin and many more (Figure 1) [11][12]. Quinazoline derivatives work as potential inhibitors of epidermal growth factor (EGF) and tyrosine kinase receptors and also display antibacterial, antitubercular and antiviral properties [13][14][15][16]. Last but not the least

A new member of the fusaricidin family – structure elucidation and synthesis of fusaricidin E

• Marcel Reimann,
• Louis P. Sandjo,
• Luis Antelo,
• Eckhard Thines,
• Isabella Siepe and
• Till Opatz

Beilstein J. Org. Chem. 2017, 13, 1430–1438, doi:10.3762/bjoc.13.140

• , six amino acids including tyrosine (Tyr), glutamine (Gln), alanine (Ala), two threonines (Thr1 and Thr2) and isoleucine (Ile) were identified. NMR experiments like COSY, NOESY and HMBC (Figure 2) clarified the sequence of the amino acids through two or three bonds correlation. The spectra revealed

Conformational study of L-methionine and L-cysteine derivatives through quantum chemical calculations and ³J_HH coupling constant analyses

• Weslley G. D. P. Silva,
• Carolyne B. Braga and
• Roberto Rittner

Beilstein J. Org. Chem. 2017, 13, 925–937, doi:10.3762/bjoc.13.94

• derivatives of tryptophan [20], phenylalanine and tyrosine [21], aspartic acid [22], proline [23] and histidine [24]. These studies have provided significant results to understand the importance of the corresponding amino acids in processes in which they take part in the polypeptide chain. Furthermore, these

Polyketide stereocontrol: a study in chemical biology

• Kira J. Weissman

Beilstein J. Org. Chem. 2017, 13, 348–371, doi:10.3762/bjoc.13.39

• residues and the direction of reduction [115] (Figure 17). When the identified position, which lies some 90 residues upstream of the conserved NADPH-binding motif, is occupied by a tyrosine residue, the methyl branch has an S configuration. In domains producing the alternative R configuration, this residue

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

• has occurred at an internal tryptophan residue of the precursor peptide. Kawaguchipeptin A Apart from the ComX pheromones, post-translational dimethylallylations of the tyrosine, threonine, serine, and tryptophan residues of cyclic peptides from cyanobacteria were reported [49][50][51]. The RiPPs

Phosphated cyclodextrins as water-soluble chiral NMR solvating agents for cationic compounds

• Cira Mollings Puentes and
• Thomas J. Wenzel

Beilstein J. Org. Chem. 2017, 13, 43–53, doi:10.3762/bjoc.13.6

• )cyclohexanemethanol (13), alanine methyl ester (14), 2-phenylglycine methyl ester (15), phenylalanine methyl ester (16), tyrosine (17), 4-chlorophenylalanine methyl ester (18), 4-chlorophenylalanine ethyl ester (19), carbobenzyloxy serine (20), 2-methylindoline (21), trans-1-amino-2-indanol (22), cis-1-amino-2

cis-Diastereoselective synthesis of chroman-fused tetralins as B-ring-modified analogues of brazilin

• Dimpee Gogoi,
• Runjun Devi,
• Pallab Pahari,
• Bipul Sarma and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2016, 12, 2816–2822, doi:10.3762/bjoc.12.280

• potentially important biological activities including the abilities to act as telomerase inhibitor and to produce DNA nicks [5][6][7]. Also, haematoxylin has recently been demonstrated to be a potent inhibitor of protein tyrosine kinase [8]. Given the broad and interesting biological activities of these two

A non-canonical peptide synthetase adenylates 3-methyl-2-oxovaleric acid for auriculamide biosynthesis

• Daniel Braga,
• Dirk Hoffmeister and
• Markus Nett

Beilstein J. Org. Chem. 2016, 12, 2766–2770, doi:10.3762/bjoc.12.274

• Herpetosiphon aurantiacus. It is composed of three unusual building blocks, including the non-proteinogenic amino acid 3-chloro-L-tyrosine, the α-hydroxy acid L-isoleucic acid, and a methylmalonyl-CoA-derived ethane unit. A candidate genetic locus for auriculamide biosynthesis was identified and encodes four

• analysis of AulA-A1. A subsequent manual inspection further revealed that the acyl-activating consensus motif is hardly conserved in AulA-A1. Moreover, the strictly invariant residue Asp413, which is essential for adenylate binding [14] was replaced by a tyrosine residue in AulA-A1. We hence concluded that

Interactions between cyclodextrins and cellular components: Towards greener medical applications?

• Loïc Leclercq

Beilstein J. Org. Chem. 2016, 12, 2644–2662, doi:10.3762/bjoc.12.261

• Phe with β-CD was estimated at 17 M−1 whereas with the Gly-Gly-Phe tripeptide, the binding constant was 89 M−1. Nevertheless, the complexation occurs when the native functional form of the proteins is unfolded. In 1996, Bekos et al. investigated the role of the L-tyrosine (Tyr) residue in the binding

Tunable microwave-assisted method for the solvent-free and catalyst-free peracetylation of natural products

• Manuela Oliverio,
• Paola Costanzo,
• Monica Nardi,
• Carla Calandruccio,
• Raffaele Salerno and
• Antonio Procopio

Beilstein J. Org. Chem. 2016, 12, 2222–2233, doi:10.3762/bjoc.12.214

• versatility of the methodology we selected a set of representative molecules of different categories (Figure 1) such as pharmaceuticals (salicylic acid (2), paracetamol (7) and salbutamol (9)), cosmetic ingredients (cytronellol (6) and myrtenol (10)), biomolecules (cholesterol (3), N-Boc- tyrosine methyl

• had a low solubility in acetic anhydride as in the case of cholesterol, N-Boc-tyrosine methyl ester and salbutamol (entries 3, 8 and 9, Table 2). Comparing to data reported in the literature [42][43], the modest yields of peracetylated product obtained in case of cholesterol 3 and salbutamol 9 were

• balanced by the absence of catalyst and by the reaction speed due to microwaves. The applied P-program was compatible with the N-Boc protecting group already present on the tyrosine methyl ester 8. Concerning salbutamol (9) the reported yield was referred to the peracetylated product 9a even if a

Rapid regio- and multi-coupling reactivity of 2,3-dibromobenzofurans with atom-economic triarylbismuths under palladium catalysis

• Maddali L. N. Rao,
• Jalindar B. Talode and
• Venneti N. Murty

Beilstein J. Org. Chem. 2016, 12, 2065–2076, doi:10.3762/bjoc.12.195

• , 2,3-disubstituted benzofurans are biologically important (Figure 1a–d) and a few reports about their isolation and synthetic methods are available [17][18][19]. Substituted benzofurans serve as antitumor agents [20], protein tyrosine phosphatase-1B inhibitors [21], antimycobacterial agents [22] and as

Catalytic Chan–Lam coupling using a ‘tube-in-tube’ reactor to deliver molecular oxygen as an oxidant

• Carl J. Mallia,
• Paul M. Burton,
• Alexander M. R. Smith,
• Gary C. Walter and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2016, 12, 1598–1607, doi:10.3762/bjoc.12.156

• gave a moderate isolated yield when coupled with 3-amino-5-bromopyridine as the nucleophile (50% yield of 23, Scheme 2) and a good isolated yield with the electron withdrawing 4-chloroaniline (71% yield of 24, Scheme 2). Using L-tyrosine methyl ester as the nucleophile with phenylboronic acid

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• consumption of hydrogen peroxide. It has been shown that the AS is substrate tolerant and accepts different hydroxylation patterns as well as glycosylations on the chalcone A and B rings [154]. However, the oxidative half-reaction only occurs with chalcones and not with other aryl substrates like L-tyrosine

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• tyrosine side chains [17] (Figure 10C). This proposal was confirmed by in vitro reconstitution of PqqE activity with PqqA [128]. Interestingly, PqqE activity is dependent on PqqD, a 10 kDa protein that functions as a chaperone that tightly binds PqqA [129]. This key interaction promotes an association with

Marine-derived myxobacteria of the suborder Nannocystineae: An underexplored source of structurally intriguing and biologically active metabolites

• Antonio Dávila-Céspedes,
• Peter Hufendiek,
• Max Crüsemann,
• Till F. Schäberle and
• Gabriele M. König

Beilstein J. Org. Chem. 2016, 12, 969–984, doi:10.3762/bjoc.12.96

• miuraenamide A (31) the absolute configuration was determined. Marfey´s method was employed to show that L-alanine and N-methyl-D-tyrosine are present. Furthermore, after acid hydrolysis, methylation and application of modified Mosher´s method the absolute configuration at the oxygen bearing C-9 was deduced as

Gold-catalyzed direct alkynylation of tryptophan in peptides using TIPS-EBX

• Gergely L. Tolnai,
• Jonathan P. Brand and
• Jerome Waser

Beilstein J. Org. Chem. 2016, 12, 745–749, doi:10.3762/bjoc.12.74

• under mild conditions and could be applied to peptides containing other nucleophilic and aromatic amino acids, such as serine, phenylalanine or tyrosine. Keywords: alkynes; C–H functionalization; gold catalysis; hypervalent iodine; peptides; Introduction Alkynes have always been important building

• ][15][16][17], whereas the more challenging modification of the electron-rich aromatic residues of tyrosine [18][19][20] and tryptophan [21][22][23][24][25][26][27][28][29][30][31] has been the focus of recent interest. As tryptophan is a rare amino acid, its functionalization is especially interesting

• other aromatic amino acids, such as phenylalanine or tyrosine (products 5c and 5d). Serine and proline containing dipeptides 5e and 5f could also be obtained in 64% and 53% yield, respectively. The reaction was therefore general for dipeptides bearing tryptophan at the C-terminus. On the other hand

Opportunities and challenges for direct C–H functionalization of piperazines

• Zhishi Ye,
• Kristen E. Gettys and
• Mingji Dai

Beilstein J. Org. Chem. 2016, 12, 702–715, doi:10.3762/bjoc.12.70

• marketed as Gleevec), a BCR-Abl tyrosine kinase inhibitor, is used in the treatment of multiple cancers with high response rate [3]. Sildenafil, sold as Viagra, is an important medication for treating erectile dysfunction as well as pulmonary arterial hypertension [4]. Indinavir, a protease inhibitor, is

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• dihydropyrans 122. They utilized the novel tyrosine-derived tertiary amine-thiourea 123 in quite low catalyst loading to catalyze the reaction between α-cyanoketones 118 and β,γ-unsaturated α-ketoesters 87 (Scheme 39) [59]. Initially a Michael reaction occurs, followed by a hemiacetalization reaction, providing

• (Scheme 42) [62]. The resulting (R)-3-nitro-2H-chromene was isolated in rather moderate optical purity. In 2010, a domino Michael hemiacetalization reaction was reported between cyclic 1,3-dicarbonyl compounds 134 and β-unsaturated α-ketoesters 87 utilizing a novel tyrosine-derived thiourea 135 (Scheme 43

Supramolecular structures based on regioisomers of cinnamyl-α-cyclodextrins – new media for capillary separation techniques

• Gabor Benkovics,
• Ondrej Hodek,
• Martina Havlikova,
• Zuzana Bosakova,
• Pavel Coufal,
• Milo Malanga,
• Eva Fenyvesi,
• Andras Darcsi,
• Szabolcs Beni and
• Jindrich Jindrich

Beilstein J. Org. Chem. 2016, 12, 97–109, doi:10.3762/bjoc.12.11

• capillary electrophoresis. The influence of the addition of 2-O-Cin-α-CD and 3-O-Cin-α-CD to the background electrolyte (BGE) and its impact on the effective mobilities of eighteen selected analytes were tested. Nine analytes were in the form of cations (aniline, antipyrine, L-histidine, DL-tyrosine, DL