Bambusuril analogs based on alternating glycoluril and xylylene units

• Tomáš Lízal and
• Vladimír Šindelář

Beilstein J. Org. Chem. 2019, 15, 1268–1274, doi:10.3762/bjoc.15.124

• common synthesis of bambusuril which employs reversible acidic conditions enabling a transformation of kinetic products to thermodynamic products [12]. Only a small quantity of macrocycle 2 in the crude mixture was identified. This minor product should be present in 4 isomeric forms, but we were not able

Electrophilic oligodeoxynucleotide synthesis using dM-Dmoc for amino protection

• Shahien Shahsavari,
• Dhananjani N. A. M. Eriyagama,
• Bhaskar Halami,
• Vagarshak Begoyan,
• Marina Tanasova,
• Jinsen Chen and
• Shiyue Fang

Beilstein J. Org. Chem. 2019, 15, 1116–1128, doi:10.3762/bjoc.15.108

• instability of the adduct under acidic conditions during ODN synthesis [7]. In recent years, applications of ODNs have extended to emerging areas such as nanotechnology [8][9], antisense drug development [10][11][12], DNA damage and repair [13][14], DNA methylation and demethylation [15][16][17][18], DNA

• protections, which contained a tertiary butyl carbamate moiety, were not completely stable under the acidic conditions needed for de-tritylation in each synthetic cycle. Once the protection was lost, in the coupling step, incoming phosphoramidites would react with the free amino groups, and branched ODNs

• that the pH of 0.4 M sodium periodate solution was around 4, and this solution did not cause premature β-elimination during oxidation. Therefore, the ODNs remained on the solid support under this significantly less acidic conditions. Because ODNs are inherently unstable under acetic conditions

Tuning the stability of alkoxyisopropyl protection groups

• Zehong Liang,
• Henna Koivikko,
• Mikko Oivanen and
• Petri Heinonen

Beilstein J. Org. Chem. 2019, 15, 746–751, doi:10.3762/bjoc.15.70

• more electron-withdrawing groups than trifluoroethanol. Nevertheless, our interest was in studying the protecting group abilities, and the studied compounds fit the most relevant reactivity area in that sense. As mentioned above, enol ether derivatives (as 8a) were formed under more acidic conditions

Synthesis of functionalized diazocines for application as building blocks in photo- and mechanoresponsive materials

• Widukind Moormann,
• Daniel Langbehn and
• Rainer Herges

Beilstein J. Org. Chem. 2019, 15, 727–732, doi:10.3762/bjoc.15.68

• reducing conditions of the azo cyclization. Moreover, the tert-butyl group can be conveniently removed under acidic conditions. As described in [27] potassium butoxide is used as a non-nucleophilic base to remove the α-toluene protons of 9a and 9b. By addition of bromine as an oxidizing agent dimers 10a

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• alternative to the strongly acidic conditions, palladium-catalyzed hydrogenolysis of the benzyloxy-substituted derivatives is possible, thus avoiding the condensation to oxazoles. Scheme 25 shows the conversion of KE52 into 1,2-diketone DK14 (compare entry 3 of Table 6). Longer reaction times lead to a

Selective benzylic C–H monooxygenation mediated by iodine oxides

• Kelsey B. LaMartina,
• Haley K. Kuck,
• Linda S. Oglesbee,
• Asma Al-Odaini and
• Nicholas C. Boaz

Beilstein J. Org. Chem. 2019, 15, 602–609, doi:10.3762/bjoc.15.55

• intermediate to decompose into phenol and acetone under acidic conditions [62]. Use of a less acidic solvent and lower reaction temperature drastically increased the selectivity for 2-phenyl-2-propanol in the NHPI-catalyzed oxidation of cumene [57]. The reason why tertiary benzylic C–H bonds, which are weaker

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

• scale, desilylation of 31 (TBAF) was a spot-to-spot conversion. Saponification of both the silylated and desilylated methyl esters with LiOH was possible, as long as very mild acidic conditions were applied on work-up. However, macrocyclisation of the TIPS-protected or the desilylated acid did not occur

Low-budget 3D-printed equipment for continuous flow reactions

• Jochen M. Neumaier,
• Amiera Madani,
• Thomas Klein and
• Thomas Ziegler

Beilstein J. Org. Chem. 2019, 15, 558–566, doi:10.3762/bjoc.15.50

• withstood the harsh acidic conditions. Work-up of the reaction mixture and isolation of acetobromo glucose 2 was done by passing the reaction mixture through a CSTR device and two syringes for phase separation [34][35]. The procedure can easily get scaled up and provides for a convenient method for

Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

• the corresponding protected derivative 30 was low (Scheme 15). Yet, this particular protecting group is easily removed under mild acidic conditions, such as diluted HCl in organic solvents (THF/MeOH) or 90% aqueous trifluoroacetic acid or hydrogenolysis. 3.3. Reduction of the pyridinium core of NR

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• . Although a cationic mechanism could have also been envisioned under the acidic conditions used, the optically enriched acetates 10d and 10e (ee > 98%) led to the corresponding alkylidenecyclopropanes 11d and 11e with complete chirality transfer (ee > 98%) at C2, thereby probing the concerted suprafacial

Regioselective addition of Grignard reagents to N-acylpyrazinium salts: synthesis of substituted 1,2-dihydropyrazines and Δ⁵-2-oxopiperazines

• Valentine R. St. Hilaire,
• William E. Hopkins,
• Yenteeo S. Miller,
• Srinivasa R. Dandepally and
• Alfred L. Williams

Beilstein J. Org. Chem. 2019, 15, 72–78, doi:10.3762/bjoc.15.8

• . Under acidic conditions, these 1,2-dihydropyrazines can be converted to substituted Δ5-2-oxopiperazines providing a simple and efficient approach towards their preparation. Keywords: N-acylpyrazinium salts; 1,2-dihydropyrazines; Grignard reagents; Δ5-2-oxopiperazines; regioselective addition

• their presence in a variety of biologically active small molecules and natural products [23][24][25][26][27][28][29][30]. We previously reported that 3-methoxy-1,2-dihydropyrazines can be easily converted to Δ5-2-oxopiperazines using 1 M HCl(aq) in methanol [9]. When we applied these acidic conditions

• , when the reaction was repeated on phenyl-substituted 1,2-dihydropyrazines containing benzyl and p-methoxybenzyl (PMB) ether groups (Table 2, entries 2 and 3). This enhancement in yield can be attributed to the benzyl and PMB groups’ better sensitivity towards removal under acidic conditions [32]. With

N-Arylphenothiazines as strong donors for photoredox catalysis – pushing the frontiers of nucleophilic addition of alcohols to alkenes

• Fabienne Speck,
• David Rombach and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2019, 15, 52–59, doi:10.3762/bjoc.15.5

• through photoredox catalysis. The currently available methods are based on a two-step procedure involving an iodoalkoxylation with NIS followed by the reduction of the formed alkyl iodide generating the product in moderate yields [20], or through the direct addition of MeOH catalyzed by either acidic

• conditions or heated ion exchange resin [21][22]. These methods are therefore not suitable for the alkoxylation of acid or base-labile substrates. To overcome the current limitations of reduction potentials of single electron transfer processes in photoredox catalysis we present herein a range of new N

Ruthenium-based olefin metathesis catalysts with monodentate unsymmetrical NHC ligands

• Veronica Paradiso,
• Chiara Costabile and
• Fabia Grisi

Beilstein J. Org. Chem. 2018, 14, 3122–3149, doi:10.3762/bjoc.14.292

• from its precursor 108 by deprotection under acidic conditions. The cis isomers 113–115 exhibited catalytic activity only at high temperatures, where they likely reassume the trans form which is characteristic for the Grubbs-type ruthenium carbene complexes. In order to develop a new structural class

Olefin metathesis catalysts embedded in β-barrel proteins: creating artificial metalloproteins for olefin metathesis

• Daniel F. Sauer,
• Johannes Schiffels,
• Takashi Hayashi,
• Ulrich Schwaneberg and
• Jun Okuda

Beilstein J. Org. Chem. 2018, 14, 2861–2871, doi:10.3762/bjoc.14.265

• achieved (Table 1, entry 1). Under slightly acidic conditions (pH 5.8), full conversion was observed with the metal complex coupled to the fully unfolded protein (Table 2, entries 2–4) [59][60]. This effect was attributed to the pH and was investigated in detail [61]. After refolding, the activity

Unnatural α-amino ethyl esters from diethyl malonate or ethyl β-bromo-α-hydroxyiminocarboxylate

• Eloi P. Coutant,
• Vincent Hervin,
• Glwadys Gagnot,
• Candice Ford,
• Racha Baatallah and
• Yves L. Janin

Beilstein J. Org. Chem. 2018, 14, 2853–2860, doi:10.3762/bjoc.14.264

• hydrochloric acid. Alternatively, oximation of the diester 51 gave 28% (from diethyl malonate) of the α-hydroxyimino ester 54, which turned out to be not stable in CDCl3 because of hydrogen chloride traces. For this reason, no attempt was made to reduce its oxime function under the acidic conditions used above

Synthesis of mono-functionalized S-diazocines via intramolecular Baeyer–Mills reactions

• Miriam Schehr,
• Daniel Hugenbusch,
• Tobias Moje,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2018, 14, 2799–2804, doi:10.3762/bjoc.14.257

• sulfur bridge is oxidized to the sulfoxide or sulfone. Hence, neither reductive nor oxidative conditions are compatible with the –CH2-S– bridge. An alternative strategy, that applies weakly acidic conditions is the condensation of aryl nitroso compounds with anilines. This Baeyer–Mills reaction was

Assembly of fully substituted triazolochromenes via a novel multicomponent reaction or mechanochemical synthesis

• Robby Vroemans,
• Yenthel Verhaegen,
• My Tran Thi Dieu and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 2689–2697, doi:10.3762/bjoc.14.246

• triazolochromene 14 and at the same time examine the stability under strong acidic conditions. Aldehyde appended triazolochromene 14 was synthesized in 85% yield, providing the proof for their relative stability under acidic conditions. Finally, triazolium salt 15 was prepared from 5a in 60% yield and renders a

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

• . Bacterial cultures were grown for eight hours in the presence of each compound, followed by extraction of the pyocyanin under acidic conditions [22]. This was then quantified by measurement of the OD520, which corresponds to absorption by the toxin. The results are shown in Figure 4, normalised by the

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

• differentially protected Fmoc-Lys-(Tfa)-OH plays a vital role in attaching fluorescent tags while growing the peptide chain in an uninterrupted manner. The methodology is versatile for solid-phase resins that are sensitive to mild and strong acidic conditions when acid-sensitive side chain amino protecting

• segment [38] without fluorescent tag using Wang resin that is cleaved in strongly acidic conditions. Contrary to the aforementioned drawbacks, the present manuscript elicits a novel synthetic strategy for building new bioconstructs with several components in a continuous process without isolation of any

• polypeptide chains 9a (Pg = Mtt) and 9b (Pg = Mmt) are generally cleaved under acidic conditions. Therefore, it becomes pertinent to analyze the stability of the chlorotrityl resin and ε-amino protecting groups in the polypeptide chains 9a and 9b to achieve our multiple objectives in a continuous synthetic

The design and synthesis of an antibacterial phenothiazine–siderophore conjugate

• Abed Tarapdar,
• James K. S. Norris,
• Oliver Sampson,
• Galina Mukamolova and
• James T. Hodgkinson

Beilstein J. Org. Chem. 2018, 14, 2646–2650, doi:10.3762/bjoc.14.242

• . However, as our final conjugate contains an aromatic halide we wanted to avoid hydrogenation as the final step and we instead chose to use the para-methoxybenzyl (PMB) protecting group which can be removed under acidic conditions. PMB-protected benzoic acid building block 7 was prepared following a

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

• pyrrolinones 6 were the minor product and the β-keto amides 5a–f were obtained in higher, although still moderate, yields (Table 1). These results indicated that the acidic conditions required for the Boc deprotection favoured the unwanted side process (Scheme 3) and the aza-Michael/retro-Mannich sequence only

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

• envisioned a milder alternative to the acidic conditions required for cyanide hydrolysis that would provide the side chain at the correct oxidation in one pot. To that end, we turned to masked acyl cyanide (MAC) chemistry [31] in which the reagent 20 acts as an acyl anion via umpolung reactivity [32]. With

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

• 2.5% water (v/v/v) for 2.5 h at room temperature (rt) and then precipitated with ice-cold diethyl ether followed by purification on RP-HPLC. Daunorubicin was attached to the purified peptides via oxime linkage that was formed under slightly acidic conditions (0.2 M NH4OAc buffer at pH 5) at rt

Semi-synthesis and insecticidal activity of spinetoram J and its D-forosamine replacement analogues

• Kai Zhang,
• Jiarong Li,
• Honglin Liu,
• Haiyou Wang and
• Lamusi A

Beilstein J. Org. Chem. 2018, 14, 2321–2330, doi:10.3762/bjoc.14.207

• ’,4’-tri-O-methylrhamnose of 5,6-dihydrospinosyn A could be hydrolyzed under strong acidic conditions to afford the aglycone of spinetoram J (compound 2). Then compound 2 was glycosylated with donor 3 to provide 4. Since the C9 glycosidic bond was more stable than the C17 glycosidic bond under weak

• sulfuric acid conditions, the 3-O-ethyl-2,4-di-O-methylrhamnose at the C17 position could be removed selectively under the weak acidic conditions to afford 5. The structure of compound 5 was also ascertained by NMR and mass spectrometry. Finally, compound 5 was glycosylated with donor 6 to provide

• ether bond at the C17 position under acidic conditions. Synthesis of spinetoram J analogues All carbohydrates and alcohols were activated by CNCCl3 with DBU as catalyst initially to afford glycoside donors, and then the 17-pseudoaglycone of spinetoram J was glycosylated with donors in the presence of

Synthesis and post-functionalization of alternate-linked-meta-para-[2ⁿ.1ⁿ]thiacyclophanes

• Wout De Leger,
• Koen Adriaensen,
• Koen Robeyns,
• Luc Van Meervelt,
• Joice Thomas,
• Björn Meijers,
• Mario Smet and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 2190–2197, doi:10.3762/bjoc.14.192

• thiamacrocycles are reported under basic conditions [31][32][33][34]. To the best of our knowledge, reactions of thiamacrocycles under acidic conditions have not been reported in contrast to homooxacalix[n]arenes, for example [35][36]. A reaction under acidic conditions with precursor 16 was investigated based on

• ] adducts. Proposed reaction mechanism towards alternate-linked-meta-para-thiacyclophanes. Attempted cyclocondensation with anisole derivative 13, products 14 and 15 were not formed. Macrocyclization under acidic conditions, with only traces of 6 and 7 observed. Post-functionalization of thiacyclophanes 6