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

• )-2 and (2S,3S)-2 in several steps including hydroxymethyl to carboxyl oxidations (Scheme 2) [50]. N-Fmoc protection of the amino group in L-serine together with transformation of the carboxylic function into an orthoester allow for the racemization-free oxidation to aldehyde 10, which was immediately

• tert-butyl ester function and finally hydrogenolytic opening of the isoxazolidine ring with simultaneous protection of the amino group (Scheme 18). By Diels–Alder reaction Acylnitroso derivative 74 prepared from methyl N-Boc-L-alaninate underwent Diels–Alder reaction with cyclopentadiene to produce

Computational characterization of enzyme-bound thiamin diphosphate reveals a surprisingly stable tricyclic state: implications for catalysis

• Ferran Planas,
• Michael J. McLeish and
• Fahmi Himo

Beilstein J. Org. Chem. 2019, 15, 145–159, doi:10.3762/bjoc.15.15

• hydrogen bonding distance of the C2 of the thiazolium ring [9][10][11][12][13][14]. While the importance of the catalytically critical ylide was readily recognized, obtaining evidence for the participation of the 4′-amino group and the imino tautomer IP proved more challenging. Initially, model compounds

• hydrogen bond between the Nε and the exocyclic N4' amino group, a bond that is not present in the other states. With that notable exception, the overall geometries of the different states are quite similar, and bond distances are also fairly consistent (Figure 3). As with model A, the AP state is found to

Asymmetric synthesis of a high added value chiral amine using immobilized ω-transaminases

• Antonella Petri,
• Valeria Colonna and
• Oreste Piccolo

Beilstein J. Org. Chem. 2019, 15, 60–66, doi:10.3762/bjoc.15.6

• more sustainable method for chiral amine production [2][3][4][5]. TAs, also known as aminotransferases, are enzymes capable of transferring an amino group from an amine donor to an acceptor containing a carbonyl functionality in the presence of pyridoxal-5'-phosphate (PLP) as a cofactor and the enzymes

Lectins of Mycobacterium tuberculosis – rarely studied proteins

• Katharina Kolbe,
• Sri Kumar Veleti,
• Norbert Reiling and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2019, 15, 1–15, doi:10.3762/bjoc.15.1

• bacterial agglutination have provided initial insights into carbohydrate specificity, sub-cellular location and functions of putative mycobacterial lectins. In the thesis of K. Kolbe various sugar derivatives were immobilized in 96 well microtiter plates via an amino group. Bacterial adhesion was studied

Green synthesis of new chiral 1-(arylamino)imidazo[2,1-a]isoindole-2,5-diones from the corresponding α-amino acid arylhydrazides in aqueous medium

• Nadia Bouzayani,
• Jamil Kraїem,
• Sylvain Marque,
• Yakdhane Kacem,
• Abel Carlin-Sinclair,
• Jérôme Marrot and
• Béchir Ben Hassine

Beilstein J. Org. Chem. 2018, 14, 2923–2930, doi:10.3762/bjoc.14.271

• . Analyzing the mechanism of the reaction between the 2-formylbenzoic acid 4 and α-amino acid arylhydrazides 3, we assumed that the first steps lead to the formation of the imine intermediate A, which is the result of the nucleophile addition of the α-amino group on the most electrophilic center in 4. This

Synthesis of indole–cycloalkyl[b]pyridine hybrids via a four-component six-step tandem process

• Muthumani Muthu,
• Rakkappan Vishnu Priya,
• Abdulrahman I. Almansour,
• Raju Suresh Kumar and
• Raju Ranjith Kumar

Beilstein J. Org. Chem. 2018, 14, 2907–2915, doi:10.3762/bjoc.14.269

• formation of (E)-3-(4-chlorophenyl)-2-(1H-indole-3-carbonyl)acrylonitrile (8). Simultaneously, the reaction of cyclododecanone (5a) with ammonium acetate affords the enamine 9. The Michael addition of 8 and the enamine 9 yields the intermediate 10. Then the amino group of 10 undergoes intramolecular

• exclusively, which is evident from the fact that the decahydrocyclododeca[b]pyridin-2-amine 13 anticipated through the intramolecular cyclization of the amino group and the CN in intermediate 10 was not formed in the reaction (Scheme 2). This one-pot four-component strategy was then employed to synthesize

Enhanced single-isomer separation and pseudoenantiomer resolution of new primary rim heterobifunctionalized α-cyclodextrin derivatives

• Iveta Tichá,
• Gábor Benkovics,
• Milo Malanga and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2018, 14, 2829–2837, doi:10.3762/bjoc.14.261

• amino group able to react with a large variety of electrophiles and is commonly used in click reactions [33]. At first, 6A-azido-α-CD 7 was prepared via bromination of α-CD (as previously described for direct bromination) [28]. Then, 6A-azido-6X-mesitylenesulfonyl-α-CD 8 was prepared (reaction 6, Scheme

Novel solid-phase strategy for the synthesis of ligand-targeted fluorescent-labelled chelating peptide conjugates as a theranostic tool for cancer

• Sagnik Sengupta,
• Mena Asha Krishnan,
• Premansh Dudhe,
• Ramesh B. Reddy,
• Bishnubasu Giri,
• Sudeshna Chattopadhyay and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2018, 14, 2665–2679, doi:10.3762/bjoc.14.244

• chelating core through carboxylic acid of lysine and attachment of fluorescent probe via ε-amino group present in the lysine amino acid. Increased hydrophobicity due to the introduction of long chain amino acids, aromatic amino acids in the targeted ligand peptide conjugate 13 would decrease the solubility

• acid attached to chlorotrityl resin via dipeptide intermediate 6 to give the tripeptide intermediate 7. The tripeptide 7 was then attached to strategic lysine amino acid, Fmoc-Lys-(Pg)-OH, whose ε-amino group is protected as either an Mtt (4-methyltrityl) or an Mmt (4-methoxytrityl) protecting group

• (4-methyltrityl) > Mmt (4-methoxytrityl). In our initial attempt, we opined that the Mtt- (4-methyltrityl-) protected ε-amino group of Fmoc-Lys-(Mtt)-OH should undergo selective cleavage under mildly acidic conditions without cleavage of polypeptide chain 9a from the resin. Selective deprotection of

Synthesis of functionalised β-keto amides by aminoacylation/domino fragmentation of β-enamino amides

• Pavel Yanev and
• Plamen Angelov

Beilstein J. Org. Chem. 2018, 14, 2602–2606, doi:10.3762/bjoc.14.238

• -protected amino acids. Domino fragmentation of the obtained intermediates leads to functionalised β-keto amides, bearing a protected amino group in their side chain. Keywords: amino acids; C-acylation; domino reaction; enamines; enaminones; keto amides; retro-Mannich; Introduction The acylation of amide

• these reagents with suitably activated amino acids, in order to prepare functionalised β-keto amides, bearing a protected amino group in their side chain. Keto amides of this type are excellent precursors to various heterocyclic systems and are also interesting as building blocks for many biologically

• favourable 5-exo-trig process, leading eventually to the pyrrolin-4-ones 6. This hypothesis is strongly supported by the behaviour of analogues 9 in which the auxiliary amino group is absent (Scheme 5). Under identical conditions (neat TFA, rt) compounds 9 do not react even after 12 hours. A reaction occurs

Synthesis of 3-aminocoumarin-N-benzylpyridinium conjugates with nanomolar inhibitory activity against acetylcholinesterase

• Nisachon Khunnawutmanotham,
• Cherdchai Laongthipparos,
• Patchreenart Saparpakorn,
• Nitirat Chimnoi and
• Supanna Techasakul

Beilstein J. Org. Chem. 2018, 14, 2545–2552, doi:10.3762/bjoc.14.231

• scopoletin portion of the compound binds to amino acid residues in PAS, whereas the N-benzylpyridinium moiety binds to those present in the CAS of AChE. To develop potent AChE inhibitors, we were interested in aminocoumarin as a replacement of scopoletin due to the presence of the amino group in the former

Synthesis of dihydroquinazolines from 2-aminobenzylamine: N³-aryl derivatives with electron-withdrawing groups

• Nadia Gruber,
• Jimena E. Díaz and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2018, 14, 2510–2519, doi:10.3762/bjoc.14.227

• others, and involve a reduction step which would be incompatible with the presence of nitro or cyano groups [5][13][14][39][68][69][70][71]. The synthetic sequence towards compounds 1 requires the chemoselective arylation of the benzylic amino group of the precursor with active haloaryl derivatives. SNAr

• ’-diacylation products were observed due to the low nucleophilicity of the secondary amino group, bearing a deactivating aromatic ring and all desired compounds were obtained with excellent yields (Table 2). Then, the microwave-assisted cyclization reaction leading to 3,4-dihydroquinazolines 1 was initially

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

• in this study. After acylation of the free amino group on the side chain of 4Lys using either acetic or butyric anhydride, the Mtt protecting group was detached. Though the application of bis-Boc-aminooxyacetic acid to incorporate the Aoa moiety provided better results (10–15% better yield according

Synthesis of indolo[1,2-c]quinazolines from 2-alkynylaniline derivatives through Pd-catalyzed indole formation/cyclization with N,N-dimethylformamide dimethyl acetal

• Antonio Arcadi,
• Sandro Cacchi,
• Giancarlo Fabrizi,
• Francesca Ghirga,
• Antonella Goggiamani,
• Antonia Iazzetti and
• Fabio Marinelli

Beilstein J. Org. Chem. 2018, 14, 2411–2417, doi:10.3762/bjoc.14.218

• of 15a to indole 14a, followed by the reaction with DMFDMA; however, an alternative path in which one amino group interact with DMFDMA to give a formamidine intermediate [27] before cyclization cannot be ruled out. Conclusion We have reported here an efficient procedure for the preparation of 12

Catalyst-free synthesis of 4-acyl-NH-1,2,3-triazoles by water-mediated cycloaddition reactions of enaminones and tosyl azide

• Lu Yang,
• Yuwei Wu,
• Yiming Yang,
• Chengping Wen and
• Jie-Ping Wan

Beilstein J. Org. Chem. 2018, 14, 2348–2353, doi:10.3762/bjoc.14.210

• -triazoline 4 which couples to water by strong hydrogen bond effect [51]. The presence of the hydrogen bonds may promote the elimination of the amino group and the acidic C–H bond at the α-position of the acyl group, which affords N-tosyl-1,2,3-triazole 5. Under the present reaction conditions, the

Cobalt-catalyzed peri-selective alkoxylation of 1-naphthylamine derivatives

• Jiao-Na Han,
• Cong Du,
• Xinju Zhu,
• Zheng-Long Wang,
• Yue Zhu,
• Zhao-Yang Chu,
• Jun-Long Niu and
• Mao-Ping Song

Beilstein J. Org. Chem. 2018, 14, 2090–2097, doi:10.3762/bjoc.14.183

• amino group at C5 of the substrate 1g was also compatible with the transformation (33%). When a methoxy group was located at the C7 site of the naphthylamine, sterically hindered product 3ha was obtained in 81%. Besides, some benzylamine derivatives (N-(1-phenylethyl)picolinamide and N

Synthesis of new p-tert-butylcalix[4]arene-based polyammonium triazolyl amphiphiles and their binding with nucleoside phosphates

• Vladimir A. Burilov,
• Guzaliya A. Fatikhova,
• Mariya N. Dokuchaeva,
• Ramil I. Nugmanov,
• Diana A. Mironova,
• Pavel V. Dorovatovskii,
• Victor N. Khrustalev,
• Svetlana E. Solovieva and
• Igor S. Antipin

Beilstein J. Org. Chem. 2018, 14, 1980–1993, doi:10.3762/bjoc.14.173

• diacetylene surfactant matrix by amphiphilic receptors with subsequent photopolymerization is a commonly used approach for the design of colorimetric analytical devices [50]. Taking into account the cationic nature of the synthesized calixarene macrocycles, the amido-diacetylene lipid bearing a terminal amino

• group N-(2-aminoethyl)pentacosa-10,12-diynamide (AEPCDA) was applied for the formation of the PDA matrix (Scheme 4). The synthesis of AEPCDA was carried out from 10,12-pentacosadiynoic acid according to the literature method [51]. AEPCDA vesicles containing calixarene 10b were produced by the well-known

Asymmetric Michael addition reactions catalyzed by calix[4]thiourea cyclohexanediamine derivatives

• Zheng-Yi Li,
• Hong-Xiao Tong,
• Yuan Chen,
• Hong-Kui Su,
• Tangxin Xiao,
• Xiao-Qiang Sun and
• Leyong Wang

Beilstein J. Org. Chem. 2018, 14, 1901–1907, doi:10.3762/bjoc.14.164

• derivatives 1–3 have been prepared. Calix[4]arene derivative 5 with an amino group on the upper rim was first prepared according to a literature report [38]. Then, the amino group was converted to an isothiocyano group through reaction with phenyl chlorothionocarbonate under alkaline conditions to obtain

Synthesis of 9-arylalkynyl- and 9-aryl-substituted benzo[b]quinolizinium derivatives by Palladium-mediated cross-coupling reactions

• Siva Sankar Murthy Bandaru,
• Darinka Dzubiel,
• Heiko Ihmels,
• Mohebodin Karbasiyoun,
• Mohamed M. A. Mahmoud and
• Carola Schulzke

Beilstein J. Org. Chem. 2018, 14, 1871–1884, doi:10.3762/bjoc.14.161

• ][46][55][56]. In the case of alkaline compound 2c, the protonation of the amino group changes the ammonium-substituted aryl substituent to an electron acceptor which leads to a blue shift of the absorption maxima (Figure 3C). The emission properties of the phenyl-substituted derivative 2a do not

• ][65][66]. The effect of the donor substituent on the emission quenching was supported by the strong increase of the emission quantum yield of 2c upon protonation of the amino group, that is, by the transformation of the donor to an acceptor substituent (Figure 5) [34]. Considering the water solubility

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

• in Table 1 (Scheme 3). The spirolactonization products 16 were isolated in excellent yields when reactions were performed with substrates 14 (R = NH2) having free amino group (Table 1, entries 1 and 2). Notably, the poor yields were observed during the spirolactonization of N-protected tyrosine

Synthesis and photophysical studies of a multivalent photoreactive Ru^II-calix[4]arene complex bearing RGD-containing cyclopentapeptides

• Sofia Kajouj,
• Lionel Marcelis,
• Alice Mattiuzzi,
• Adrien Grassin,
• Damien Dufour,
• Pierre Van Antwerpen,
• Didier Boturyn,
• Eric Defrancq,
• Mathieu Surin,
• Julien De Winter,
• Pascal Gerbaux,
• Ivan Jabin and
• Cécile Moucheron

Beilstein J. Org. Chem. 2018, 14, 1758–1768, doi:10.3762/bjoc.14.150

• in the IR spectrum of 4. Phenanthroline derivative 5 was synthesized from 5-glycinamido-1,10-phenanthroline in a two-step sequence consisting of a peptide-type coupling reaction with a Boc-protected glycine N-hydrosuccinimide ester followed by the deprotection of the amino group (see Supporting

Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

• NH group. Hence, the trichloroethoxycarbonyl (Troc) protection/activation of the amino group of questiomycin 119 allowed Igarashi et al. to access the N-glucosylated derivative 120 in good yield and complete β-stereoselectivity from hemiacetal 1 (Scheme 23) [88]. Also some aza-heterocycles bearing a

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

• drug conjugates. Dox has three potential conjugation sites; i) a primary OH group at C-14 on the aglycone part, which is suitable for ester bond formation, ii) an oxo group at C-13 is available for the generation of an oxime linkage and iii) the amino group on the daunosamine sugar moiety, which can be

• molecules were also prepared. When the native GnRH-III was used, an additional Lys was incorporated to the side chain of Lys in position 8. A Dau was attached to its ε-amino group and the second Dau (12) or the Mtx (13) was connected to the α-amino group. In conjugate 14, the two Dau molecules were linked

• fragmentation of the conjugate between the aglycon part and sugar moiety resulted in fragments in which the peptide was attached either the aglycon OH group or the amino group of sugar moiety [23]. When unprotected Dox was used for the reaction with glutaric anhydride, the amino group was modified with glutaric

Acyl-group specificity of AHL synthases involved in quorum-sensing in Roseobacter group bacteria

• Lisa Ziesche,
• Jan Rinkel,
• Jeroen S. Dickschat and
• Stefan Schulz

Beilstein J. Org. Chem. 2018, 14, 1309–1316, doi:10.3762/bjoc.14.112

• . gallaeciensis BS107 produced eight different AHLs [8]. The biosynthesis of AHLs is mediated by the enzyme LuxI or its homologs, and often accompanied by a regulator protein, LuxR [18][19]. An ACP-bound fatty acid acyl group 1 is transferred onto the amino group of S-adenosylmethionine (SAM, 2) that is followed

Oligonucleotide analogues with cationic backbone linkages

• Melissa Meng and
• Christian Ducho

Beilstein J. Org. Chem. 2018, 14, 1293–1308, doi:10.3762/bjoc.14.111

• was then converted into a reactive carbodiimide 24 and coupled to a terminal amino group of the solid phase 25 (Scheme 2). This coupling furnished solid phase-attached intermediate 26, which was Fmoc-deprotected to the amine 27. Iterative repetition of this coupling-deprotection cycle gave oligomer 28

• '-amino-5'-deoxythymidine attached to CPG (37) served as the solid phase. The construction of the oligomer, achieved in 3'→5' direction, was based on the coupling of 3'-isothiocyanate 38 with the 5'-amino group of 37 to give 39 and, after acidic MMTr cleavage, 40. Iterative repetition of this coupling

• 46 and 47 [15][16][17][18][19][20][21][22] furnished the structure of an 'NAA-modified oligonucleotide' 48 (Figure 5). The 6'-amino group of the NAA-modification is positively charged at physiological pH values, thus providing a (partially) zwitterionic backbone structure if some phosphate diester

A survey of chiral hypervalent iodine reagents in asymmetric synthesis

• Soumen Ghosh,
• Suman Pradhan and
• Indranil Chatterjee

Beilstein J. Org. Chem. 2018, 14, 1244–1262, doi:10.3762/bjoc.14.107

• oxy/amino group followed by the nucleophilic addition of the aryl group delivers the desired products 54. The key to success also lies on the enantiotopic face discrimination of the alkene by the lactate-based chiral iodine reagent. This difunctionalization strategy was further showcased by Muñiz et