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

• dimethyl sulfate mainly N-methylation was observed accompanied by a small amount of the N,O-dimethylquinolonium ion. Pure NMe-HHQ (2) was obtained in moderate yield of 51% by column chromatography (Scheme 1). Selective O-methylation of an AQ has been reported using diazomethane [1]. To avoid explosive

• separated from the N-methylation product by column chromatography and could be isolated in 32% yield. Surprisingly, the N-methylated product under these conditions was not NMe-HHQ (2), but instead a second methylation in the benzylic position had occurred to give N-methyl-2-(1-methylheptyl)-4(1H)-quinolone

• conditions to give a mixture of OMe-3I-HHQ (9, 21%) and NMe-3I-HHQ (10, 24%, Scheme 3). Interestingly, in the case of 3I-HHQ (8) the ratio of N-methylation versus O-methylation was almost 1:1 and no further methylation of 10 in the benzylic position was observed. With the methylated compounds 9 and 10 in

Phosphodiester models for cleavage of nucleic acids

• Satu Mikkola,
• Tuomas Lönnberg and
• Harri Lönnberg

Beilstein J. Org. Chem. 2018, 14, 803–837, doi:10.3762/bjoc.14.68

Synthesis of benzannelated sultams by intramolecular Pd-catalyzed arylation of tertiary sulfonamides

• Valentin A. Rassadin,
• Mirko Scholz,
• Anastasiia A. Klochkova,
• Armin de Meijere and
• Victor V. Sokolov

Beilstein J. Org. Chem. 2017, 13, 1932–1939, doi:10.3762/bjoc.13.187

• methyl iodide (Scheme 2). Unfortunately, this apparently simple transformation yielded a mixture of C-, N- and C,N-methylation products due to similar reactivities of the C- and N-nucleophilic centers in 3a. At best, the tertiary sulfonamide 5 was isolated in 32% yield. In contrast to the behavior of 3a

DMAP-assisted sulfonylation as an efficient step for the methylation of primary amine motifs on solid support

• Johnny N. Naoum,
• Koushik Chandra,
• Dorit Shemesh,
• R. Benny Gerber,
• Chaim Gilon and
• Mattan Hurevich

Beilstein J. Org. Chem. 2017, 13, 806–816, doi:10.3762/bjoc.13.81

• an explanation by showing that the energy barrier of the DMAP intermediate is significantly lower than the one of the collidine. We demonstrate that using DMAP as a sole additive in the sulfonylation step results in an overall effective and regioselective N-methylation. The method presented herein

• proved highly efficient in solid-phase synthesis of a somatostatin analogue bearing three Nα-methylation sites that could not be synthesized using the previously described state-of-the-art methods. Keywords: N-methylation; nucleophilic addition; solid phase; somatostatin; sulfonylation; Introduction

• Scanlan adjusted the o-NBS strategy to solid-phase synthesis and introduced a general three-step procedure for Nα-mono-methylation of amino acids on solid support that was based on the work of Fukuyama [17][22][23]. Kessler and co-workers presented a time saving and cost effective three-step N-methylation

Derivatives of the triaminoguanidinium ion, 5. Acylation of triaminoguanidines leading to symmetrical tris(acylamino)guanidines and mesoionic 1,2,4-triazolium-3-aminides

• Jan Szabo,
• Julian Greiner and
• Gerhard Maas

Beilstein J. Org. Chem. 2017, 13, 579–588, doi:10.3762/bjoc.13.57

• maximum in the series R = CH3 < phenyl ≈ 3,4,5-trimethoxyphenyl < 4-nitrophenyl. For 7a–c, this absorption band could result from a charge transfer between the amidinate moiety, representing the HOMO of the mesoionic system, and an unoccupied π-orbital of the C(=O)Ar group. Upon N-protonation or N

• -methylation, the mesoionic system loses its betainic character and a 1,2,4-triazolium ion is formed. This is accompanied by the disappearance of the long-wavelength absorption in the electronic spectra, leaving colorless salts 8. Conclusion We have found that triaminoguanidine, generated from its

Continuous N-alkylation reactions of amino alcohols using γ-Al₂O₃ and supercritical CO₂: unexpected formation of cyclic ureas and urethanes by reaction with CO₂

• Emilia S. Streng,
• Darren S. Lee,
• Michael W. George and
• Martyn Poliakoff

Beilstein J. Org. Chem. 2017, 13, 329–337, doi:10.3762/bjoc.13.36

• ), which was formed by both O- and N-methylation of the starting material. Self-optimisation of the reaction of this substrate was performed in order to try and locate the optimal conditions for the highest yield of 6. Within the parameters explored, it was found that higher reaction temperatures increased

• min−1, 100 bar, when applicable 0.5 mL min−1 CO2. Diagram of the high pressure equipment used in the experiments. Target reaction – intramolecular cyclisation of 1 followed by N-methylation with methanol to yield 2b. Cyclisation and N-alkylation of 1,4- and 1,6-amino alcohols. a) Reactions

An intramolecular C–N cross-coupling of β-enaminones: a simple and efficient way to precursors of some alkaloids of Galipea officinalis

• Hana Doušová,
• Radim Horák,
• Zdeňka Růžičková and
• Petr Šimůnek

Beilstein J. Org. Chem. 2015, 11, 884–892, doi:10.3762/bjoc.11.99

• ]. As part of our ongoing interest in the preparation of polarized ethylenes and their application in organic synthesis, we have been attracted by the procedure published by Zhou [30]. Here, the authors used heterocyclic enaminone 1b as the reactant for an asymmetric reduction followed by N-methylation

Structure of 1,5-benzodiazepinones in the solid state and in solution: Effect of the fluorination in the six-membered ring

• Marta Pérez-Torralba,
• Rosa M. Claramunt,
• M. Ángeles García,
• Concepción López,
• M. Carmen Torralba,
• M. Rosario Torres,
• Ibon Alkorta and
• José Elguero

Beilstein J. Org. Chem. 2013, 9, 2156–2167, doi:10.3762/bjoc.9.253

• to compound 1 indicate a greater deformation in the seven-membered ring owing to the presence of the N-methyl substituent. The N-methylation prevents the dimerization by hydrogen bonding leading to a very different packing. Therefore, the most significant intermolecular interaction is the F–F contact

• ) > b (18 kJ mol−1 in average), the other tautomers having considerably higher energies. Always tautomer b is destabilized by N-methylation (in average, 8.4 kJ mol−1) probably due to a steric effect; the conjugated tautomer b tends to be planar and this is indeed the case for 1H-derivatives 1b, 3b and

• -2-one) [27]. When using calculated values it is possible to analyze the main effects on the barriers that in the present case are three: i) N-methylation; ii) 6,7,8,9-tetrafluorination; iii) the substituent at position 4 (CH3 or C6H5). This last effect is negligible, the other two interact, then a

Amyloid-β probes: Review of structure–activity and brain-kinetics relationships

• Todd J. Eckroat,
• Abdelrahman S. Mayhoub and
• Sylvie Garneau-Tsodikova

Beilstein J. Org. Chem. 2013, 9, 1012–1044, doi:10.3762/bjoc.9.116

• catalyzed Suzuki coupling of the starting halide 73 and boronic acid 74 followed by N-methylation of 75 with [3H]methyl iodide and O-demethylation with sodium thiophenoxide (Scheme 6C). Compound 57 showed high affinity for Aβ1-40 fibrils in vitro (Kd = 8.4 nM) and lower background binding levels than 56c

One-pot tandem cyclization of enantiopure asymmetric cis-2,5-disubstituted pyrrolidines: Facile access to chiral 10-heteroazatriquinanes

• Ping-An Wang,
• Sheng-Yong Zhang and
• Henri B. Kagan

Beilstein J. Org. Chem. 2013, 9, 265–269, doi:10.3762/bjoc.9.32

• CH2Cl2, suitable for X-ray diffraction analysis. It was found that the ring-closing reaction took place during the heating process following N-methylation to provide the rigid 1-oxo-3-aza-10-azaquinane skeleton 7b as its ammonium salt. Compound 7b contains four stereogenic centers, and their

Glycosylation efficiencies on different solid supports using a hydrogenolysis-labile linker

• Mayeul Collot,
• Steffen Eller,
• Markus Weishaupt and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2013, 9, 97–105, doi:10.3762/bjoc.9.13

• /ethyl acetate (3:2), N-methylation and N-formylation were observed (Supporting Information File 1). Considering prior evidence that methanol can generate formaldehyde in the presence of Pd(0) by an oxidative addition mechanism [43][44] and the observation that apolar solvents cause N-formylation during

Mutational analysis of a phenazine biosynthetic gene cluster in Streptomyces anulatus 9663

• Orwah Saleh,
• Katrin Flinspach,
• Lucia Westrich,
• Andreas Kulik,
• Bertolt Gust,
• Hans-Peter Fiedler and
• Lutz Heide

Beilstein J. Org. Chem. 2012, 8, 501–513, doi:10.3762/bjoc.8.57

• methyltransferase that catalyzes the N-methylation reaction during the biosynthesis of pyocyanine in Pseudomonas. Also, Streptomyces anulatus produces an N-methylated phenazine, i.e., endophenazine B [22]. The heterologous expression strain S. coelicolor M512 containing the endophenazine cluster from S. anulatus

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

• ) with cyclohexan-1,3-dione (Scheme 38). Classical N-methylation with dimethyl sulfate followed by introduction of an exocyclic double bond using paraformaldehyde in DMF under acidic conditions furnishes the Michael acceptor 189, which then undergoes conjugate addition with various amines (Scheme 38

Convenient method for preparing benzyl ethers and esters using 2-benzyloxypyridine

• Susana S. Lopez and
• Gregory B. Dudley

Beilstein J. Org. Chem. 2008, 4, No. 44, doi:10.3762/bjoc.4.44

• new reagent for the synthesis of benzyl ethers and esters. This article provides a revised benzyl transfer protocol in which N-methylation of 2-benzyloxypyridine delivers the active reagent in situ. Observations on the appropriate choice of solvent (toluene vs. trifluorotoluene) and the extension of

• [14][15] in Scheme 1). N-Methylation of 2-benzyloxypyridine (2) furnishes crystalline 1, which is collected by filtration and may be stored for later use [16][17][18]. For routine and repeated use, isolation and storage of 1 is most convenient. Alternatively, in situ activation of 2 without isolation

• acid-labile Boc group and the base-labile β-hydroxy ester. Minor modification of the above procedure renders it suitable for the formation of benzyl esters from carboxylic acids (Scheme 3). In order to avoid the potential for competing N-methylation of triethylamine, which is the optimal acid scavenger