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

Synthesis of 1,4-imino-L-lyxitols modified at C-5 and their evaluation as inhibitors of GH38 α-mannosidases

• Maroš Bella,
• Sergej Šesták,
• Ján Moncoľ,
• Miroslav Koóš and
• Monika Poláková

Beilstein J. Org. Chem. 2018, 14, 2156–2162, doi:10.3762/bjoc.14.189

• protecting trityl group under acidic conditions followed by tosylation of the liberated hydroxy group with TsCl in the presence of DMAP as a base. Thus, required tosyl derivative 8 was obtained in 76% yield in two steps. It should be emphasized that tosylation in the presence of commonly used bases such as

D-Fructose-based spiro-fused PHOX ligands: synthesis and application in enantioselective allylic alkylation

• Michael R. Imrich,
• Jochen Kraft,
• Cäcilia Maichle-Mössmer and
• Thomas Ziegler

Beilstein J. Org. Chem. 2018, 14, 2082–2089, doi:10.3762/bjoc.14.182

• was converted to 6a as previously described in [23]. Next, the isopropylidene group at positions 4 and 5 were removed under acidic conditions and the resulting intermediate 7a was converted to 7b with identical protecting groups at positions 3, 4 and 5 [24][25][26][27][28]. In order to obtain D

• is the Ritter reaction of suitable carbohydrate derivatives with nitriles under Lewis-acidic conditions [29][30][31]. Recently, Vangala and Shinde reported the synthesis of spirocyclic 2-substituted 2-oxazoline ribosides from 1,2-isopropylidene-protected furanosides [32]. In our case, however, only

Rational design of boron-dipyrromethene (BODIPY) reporter dyes for cucurbit[7]uril

• Mohammad A. Alnajjar,
• Jürgen Bartelmeß,
• Robert Hein,
• Pichandi Ashokkumar,
• Mohamed Nilam,
• Werner M. Nau,
• Knut Rurack and
• Andreas Hennig

Beilstein J. Org. Chem. 2018, 14, 1961–1971, doi:10.3762/bjoc.14.171

• )benzaldehyde with 2,4-dimethylpyrrole to afford the BODIPY dye by condensation under acidic conditions (route A) [32][33]. Since all efforts to obtain 2 via route A were not successful, even using Finkelstein conditions in aprotic solvents with high boiling points with various bases [34][35], BDP-NH2 was

Preparation and X-ray structure of 2-iodoxybenzenesulfonic acid (IBS) – a powerful hypervalent iodine(V) oxidant

• Irina A. Mironova,
• Pavel S. Postnikov,
• Rosa Y. Yusubova,
• Akira Yoshimura,
• Thomas Wirth,
• Viktor V. Zhdankin,
• Victor N. Nemykin and
• Mekhman S. Yusubov

Beilstein J. Org. Chem. 2018, 14, 1854–1858, doi:10.3762/bjoc.14.159

• interactions. Furthermore, a new method for the preparation of the reduced form of IBS, 2-iodosylbenzenesulfonic acid, by using periodic acid as an oxidant, has been developed. It has been demonstrated that the oxidation of free 2-iodobenzenesulfonic acid under acidic conditions affords an iodine(III

• salt) in neutral aqueous solution or 2-iodosylbenzenesulfonic acid under acidic conditions. This result can be explained by a greater stability of the heterocyclic molecule of 2-iodosylbenzenesulfonic acid towards disproportionation in comparison to the unknown salt of 2-iodosylbenzenesulfonic acid

• of IBS, 2-iodosylbenzenesulfonic acid, by using periodic acid as an oxidant. We have demonstrated that the oxidation of free 2-iodobenzenesulfonic acid under acidic conditions affords an iodine(III) heterocycle, while the oxidation of sodium 2-iodobenzenesulfonate in neutral aqueous solution gives

Efficient catenane synthesis by cucurbit[6]uril-mediated azide–alkyne cycloaddition

• Antony Wing Hung Ng,
• Chi-Chung Yee,
• Kai Wang and
• Ho Yu Au-Yeung

Beilstein J. Org. Chem. 2018, 14, 1846–1853, doi:10.3762/bjoc.14.158

• Scheme 1. The secondary amines are designed to form ammoniums that will strongly bind to CB[6] through ion-dipole interactions under aqueous acidic conditions. Upon formation of the inclusion complex with CB[6], the azide and alkyne functionalities inside the CB[6] cavity will be placed in close

An amine protecting group deprotectable under nearly neutral oxidative conditions

• Shahien Shahsavari,
• Chase McNamara,
• Mark Sylvester,
• Emily Bromley,
• Savannah Joslin,
• Bao-Yuan Lu and
• Shiyue Fang

Beilstein J. Org. Chem. 2018, 14, 1750–1757, doi:10.3762/bjoc.14.149

• products by sodium periodate and its reduced products. In addition, we also found that oxidation of sulfides by sodium periodate was significantly slower under basic conditions than under neutral and acidic conditions. To demonstrate the feasibility of selective deprotection of dM-Dmoc protected amines in

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• reasonable yields over shorter reaction times and at low catalyst loading. The regioselectivity of the reactions was strongly dependent on the acidity or basicity of the reaction conditions. Under acidic conditions, nucleophilic attack of the thiol at the more-substituted α-carbon was favored while under

A selective removal of the secondary hydroxy group from ortho-dithioacetal-substituted diarylmethanols

• Anna Czarnecka,
• Emilia Kowalska,
• Agnieszka Bodzioch,
• Joanna Skalik,
• Marek Koprowski,
• Krzysztof Owsianik and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2018, 14, 1229–1237, doi:10.3762/bjoc.14.105

• have been observed in these cases [32][33]. It has also been reported that ortho-substituents on aryl moieties give lower yields in the reduction processes [33]. Moreover, the OH reduction under acidic conditions cannot be carried out in the presence of other sensitive functional groups. For instance

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• of p-toluenesulfonic acid (p-TsOH), the reduction of 175 with lithium aluminum hydride afforded the intermediate 176, which was converted to 2,3-benzotropone (12) under acidic conditions. 3.2. Reactions of 2,3-benzotropone (12) 3.2.1. Reactions via a carbonyl group: Among the most common reactions

• shown in Scheme 6, the synthesis of the bicyclic ring 33 from the dichlorocarbene adduct of oxobenzonorbornadiene 31 has also been reported by Ranken’s group in two steps [53]. Hydrolysis of 33 in water under acidic conditions led to 2-chlorobenzotropone 309 in 20% yield (Scheme 53) [53]. A multistep

Mechanochemistry of nucleosides, nucleotides and related materials

• Olga Eguaogie,
• Joseph S. Vyle,
• Patrick F. Conlon,
• Manuela A. Gîlea and
• Yipei Liang

Beilstein J. Org. Chem. 2018, 14, 955–970, doi:10.3762/bjoc.14.81

• conditions was exploited to prepare pyrophosphorothiolate-linked dinucleoside cap analogues. Such materials had previously been inaccessible via this route due to the lability of intermediate phosphorothiolate monoesters under acidic conditions [55]. In contrast, the corresponding persilylated derivatives

On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site

• Eirinaios I. Vrettos,
• Gábor Mező and
• Andreas G. Tzakos

Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80

Methyl isocyanide as a convertible functional group for the synthesis of spirocyclic oxindole γ-lactams via post-Ugi-4CR/transamidation/cyclization in a one-pot, three-step sequence

• Amarendar Reddy Maddirala and
• Peter R. Andreana

Beilstein J. Org. Chem. 2018, 14, 875–883, doi:10.3762/bjoc.14.74

• performed under acidic conditions, particularly in the presence of TFA, the reaction led to 3-substituted 2-indolinones in a three-step process [40]. In this work, we discovered that methyl isocyanide [43] operates under a mechanism of convertible isocyanides (CICs) [44][45][46][47][48][49], and could be

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

• incorporated in position 4 and Fmoc-Lys(Mtt)-OH in position 8. After peptide chain elongation the Dde group was removed and 4Lys was butyrylated by using butyric anhydride. Afterwards, the Mtt group was cleaved under mild acidic conditions, followed by Boc-Aoa-OH coupling. After cleavage from the resin with an

Enzyme-free genetic copying of DNA and RNA sequences

• Marilyne Sosson and
• Clemens Richert

Beilstein J. Org. Chem. 2018, 14, 603–617, doi:10.3762/bjoc.14.47

• the extension of RNA primers with ribonucleotides without preactivation lies in the different pH optima of the two reactions. The activation, which now has to occur in the same solution as the extension, is most easily performed under slightly acidic conditions, whereas the extension reaction is

Diastereoselective auxiliary- and catalyst-controlled intramolecular aza-Michael reaction for the elaboration of enantioenriched 3-substituted isoindolinones. Application to the synthesis of a new pazinaclone analogue

• Romain Sallio,
• Stéphane Lebrun,
• Frédéric Capet,
• Francine Agbossou-Niedercorn,
• Christophe Michon and
• Eric Deniau

Beilstein J. Org. Chem. 2018, 14, 593–602, doi:10.3762/bjoc.14.46

• targeted NH-free isoindolinones, the cleavage of the (R)-α-methylbenzyl chiral auxiliary was performed in acidic conditions but the reactions proved to be ineffective. However, a change in our models for the more electron rich (R)-α-methyl-para-methoxybenzyl group resulted in a straightforward and

• selective cleavage in mild acidic conditions without racemization (Scheme 4). Indeed, further cleavage of the α-methyl-para-methoxyphenyl chiral auxiliary in protected isoindolinones 4a–c, 4e and 5 resulted in the corresponding NH-free lactams 1a–c, 1e and 2 without any racemization (Scheme 4). A subsequent

Synthetic and semi-synthetic approaches to unprotected N-glycan oxazolines

• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 416–429, doi:10.3762/bjoc.14.30

• sugars as substrates presents some limitations, as any remaining protecting groups must be removed in a subsequent step. Firstly, and most importantly, glycosyl oxazolines are extremely labile to acidic hydrolysis, and so this approach precludes the use of any OH-protecting groups that require acidic

• conditions for their cleavage. Secondly some glycosyl oxazolines are also prone to reductive cleavage by catalytic hydrogenation [41], presenting a significant further limitation as to which OH-protecting groups may be employed. Most of the reports in the literature have therefore used a protecting group

Novel amide-functionalized chloramphenicol base bifunctional organocatalysts for enantioselective alcoholysis of meso-cyclic anhydrides

• Lingjun Xu,
• Shuwen Han,
• Linjie Yan,
• Haifeng Wang,
• Haihui Peng and
• Fener Chen

Beilstein J. Org. Chem. 2018, 14, 309–317, doi:10.3762/bjoc.14.19

• rearrangement in 75% yield over two steps. After Pd/C-catalyzed hydrogenative deprotection of hydroxy group in methanol under acidic conditions, the corresponding alcohol 12 was transferred to the product 13 via acid-promoted deprotection. A single recrystallization from ethanol allowed 13 to be isolated with

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

• carried out the reaction under acidic conditions expecting the formation of the regioisomeric 3/5-aminopyrazoles 16/91 but the reaction under the influence of conc. HNO3 resulted in the formation of an unexpected product which was characterized as 4,7-dihydropyrazolo[3,4-b]pyridine 92 through rigorous

Nucleophilic fluoroalkylation/cyclization route to fluorinated phthalides

• Masanori Inaba,
• Tatsuya Sakai,
• Shun Shinada,
• Tsuyuka Sugiishi,
• Yuta Nishina,
• Norio Shibata and
• Hideki Amii

Beilstein J. Org. Chem. 2018, 14, 182–186, doi:10.3762/bjoc.14.12

• work-up under acidic conditions, 3-(trifluoromethyl)-1(3H)-isobenzofuranone (1a) was obtained in 99% NMR yield (95% isolated yield) (Table 1, entry 1). As a good alternative activator of CF3–SiMe3, the use of a Lewis base such as triethylamine [22][23] worked well for the synthesis of 3

Progress in copper-catalyzed trifluoromethylation

• Guan-bao Li,
• Chao Zhang,
• Chun Song and
• Yu-dao Ma

Beilstein J. Org. Chem. 2018, 14, 155–181, doi:10.3762/bjoc.14.11

• para-benzylic position of the hydroxy group (Scheme 32). It is notable that the bulky tert-butyl group was introduced to suppress side reactions, which could be removed under acidic conditions. The solvent was critical in terms of product switching; the trifluoromethylation of aromatic C–H occurred in

From dipivaloylketene to tetraoxaadamantanes

• Gert Kollenz and
• Curt Wentrup

Beilstein J. Org. Chem. 2018, 14, 1–10, doi:10.3762/bjoc.14.1

• ]nonadienes (bisdioxines) 4. When arylamines are used as the nucleophiles under neutral conditions, decarboxylation occurs during the formation of bisdioxines 8. However, when water or alcohols are added to 3 under acidic conditions, bisdioxine-carboxylic acids and esters 10 and 11 are obtained. Acid

• (Scheme 4). When this reaction is carried out under neutral conditions (with arylamines), decarboxylation of the carboxylic acid function occurs, yielding 8, but under acidic conditions (with alcohols and water) the acid function is preserved, yielding 10 and 11. Addition of water to one of the acrylic

• -type double bonds in the bisdioxines under acidic conditions generates a tertiary alcohol, which again undergoes a transannular oxa-Michael-type ring closure forming a tetraoxaadamantane. Free carboxylic acid functions are decarboxylated in this process (Scheme 7), but amide and ester functions are