Syntheses of 2-substituted 1-amino-4-bromoanthraquinones (bromaminic acid analogues) – precursors for dyes and drugs

• Enas M. Malik,
• Younis Baqi and
• Christa E. Müller

Beilstein J. Org. Chem. 2015, 11, 2326–2333, doi:10.3762/bjoc.11.253

• formaldehyde under alkaline conditions to yield 1-amino-2-hydroxymethylanthraquinone (5) in good isolated yield [56] (Scheme 2). Compound 5 was subjected to bromination using bromine in N,N-dimethylformamide (DMF). The reaction proceeded smoothly at room temperature affording 1-amino-4-bromo-2

• -hydroxymethylanthraquinone (6) in high yield (Scheme 2 and Table 1). The synthesis of compound 6 had previously been described in the literature by treating bromaminic acid sodium salt (2) with sodium dithionite and formaldehyde under alkaline conditions [61]. We initially tried to reproduce the published procedure, however

Cholesterol lowering effects of mono-lactose-appended β-cyclodextrin in Niemann–Pick type C disease-like HepG2 cells

• Keiichi Motoyama,
• Yumi Hirai,
• Rena Nishiyama,
• Yuki Maeda,
• Taishi Higashi,
• Yoichi Ishitsuka,
• Yuki Kondo,
• Tetsumi Irie,
• Takumi Era and
• Hidetoshi Arima

Beilstein J. Org. Chem. 2015, 11, 2079–2086, doi:10.3762/bjoc.11.224

• treatment with 150 μL of cell-based assay fixative solution (4% formaldehyde), 150 μL of cholesterol detection assay buffer containing 50 μg/mL of Filipin III was added and further incubated at 37 °C for 1 h. After the cells were washed, the fluorescence derived from Filipin III in U18666A-treated HepG2

Engineering Pichia pastoris for improved NADH regeneration: A novel chassis strain for whole-cell catalysis

• Martina Geier,
• Christoph Brandner,
• Gernot A. Strohmeier,
• Mélanie Hall,
• Franz S. Hartner and
• Anton Glieder

Beilstein J. Org. Chem. 2015, 11, 1741–1748, doi:10.3762/bjoc.11.190

• regeneration enzymes such as D-glucose-6-phosphate dehydrogenase, formaldehyde dehydrogenase and formate reductase can be co-expressed ensuring cofactor supply also in non-growing, resting cells. In addition to the cofactor supply, the application of whole cells circumvents time-consuming enzyme isolation and

• oxidized by alcohol oxidase (AOX) to formaldehyde, which is further metabolized either in the assimilatory or in the dissimilatory pathway. In the latter one, formaldehyde spontaneously reacts with glutathione to S-hydroxymethylglutathione which is oxidized in a first step by the glutathione- and NAD

• +-dependent enzyme formaldehyde dehydrogenase (FLD) to S-formylglutathione. S-Formylglutathione hydrolase (FGH) then hydrolyses this compound to formate and glutathione. In a second NAD+-dependent step, formate is oxidized to CO2 by formate dehydrogenase (FDH). Thus, 2 equivalents of the cofactor NADH are

Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

• Louis P. Sandjo,
• Victor Kuete and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2015, 11, 1667–1699, doi:10.3762/bjoc.11.183

•  9) were presumably formed by reaction of a related benzophenanthroline (styelsamine D, 6) with cysteine and formaldehyde, respectively [47]. This reaction was followed by cyclization and oxidation to afford the alkaloids (Figure 9). The analysis of different biosynthesis pathways clearly suggested

• tryptophan and dopamine as precursors of pyridoacridines. Thus, formaldehyde and amino acids are responsible for the thiazole, piperidone, oxathiolane and thiomorpholinone rings found in pyridoacridines structures. Biological activity The biological activity of pyridoacridines, including both natural and

Robust bifunctional aluminium–salen catalysts for the preparation of cyclic carbonates from carbon dioxide and epoxides

• Yuri A. Rulev,
• Zalina Gugkaeva,
• Victor I. Maleev,
• Michael North and
• Yuri N. Belokon

Beilstein J. Org. Chem. 2015, 11, 1614–1623, doi:10.3762/bjoc.11.176

• ). 3-(tert-Butyl)-5-(dimethylamino)-2-hydroxybenzaldehyde (6) Prepared by a modified literature procedure [28]. Pd/C (10%, 100 mg) was added to a solution of 3-(tert-butyl)-2-hydroxy-5-nitrobenzaldehyde 5 (200 mg, 0.9 mmol) and 40% aqueous formaldehyde (4.5 mL) in ethanol (20 mL). The reaction mixture

A new and efficient procedure for the synthesis of hexahydropyrimidine-fused 1,4-naphthoquinones

• Marcelo Isidoro P. Reis,
• Vinícius R. Campos,
• Jackson A. L. C. Resende,
• Fernando C. Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2015, 11, 1235–1240, doi:10.3762/bjoc.11.137

• unsymmetrical hexahydropyrimidine-fused 1,2- and 1,4-naphthoquinones by the reaction of 4-amino-l,2-naphthoquinone and 2-amino-1,4-naphthoquinone with amines and formaldehyde in moderate yields [37]. Ohta et al. studied the nucleophilic addition reaction of methylamine to 2-bromo-3-hydroxymethyl-1,4

• synthetic and biological applications [40]. These substances are easily prepared from commercially available amines and formaldehyde in toluene in yields ranging from 75–90%. Barluenga and coworkers [41] have previously shown that 1,3,5-triazinanes undergo fragmentation at elevated temperatures to form 3

• equivalents of alkyl- or aryl-formimines in situ. The latter compounds may serve as electrophilic agents for aminoalkylation reactions. Our research group also investigated the aminoalkylation of 2-amino-1,4-naphthoquinone with formaldehyde under microwave irradiation to produce two series of N,O-acetals and

NAA-modified DNA oligonucleotides with zwitterionic backbones: stereoselective synthesis of A–T phosphoramidite building blocks

• Boris Schmidtgall,
• Claudia Höbartner and
• Christian Ducho

Beilstein J. Org. Chem. 2015, 11, 50–60, doi:10.3762/bjoc.11.8

• starting material, one challenge was to avoid unwanted side reactions resulting from the generation of formaldehyde in the reaction mixture. Hydrogenolysis of the BOM group affords toluene and formaldehyde as byproducts, and the Cbz-deprotected 6'-amino group can undergo unwanted reductive amination, i.e

• ., methylation, with the liberated formaldehyde. Our method to prevent this side reaction was to include an excess of n-butylamine as an additive in the reaction mixture of the hydrogenolysis step. This way, the formaldehyde methylated the added n-butylamine, furnishing a reasonably volatile byproduct [38][48

Encapsulation of biocides by cyclodextrins: toward synergistic effects against pathogens

• Véronique Nardello-Rataj and
• Loïc Leclercq

Beilstein J. Org. Chem. 2014, 10, 2603–2622, doi:10.3762/bjoc.10.273

• environment [23]. The toxicity of some biocides has been particularly well described. As examples glutaraldehyde and amphiphilic ammonium have been associated with dermatitis [24][25]. Toxicity, hypersensitivity and irritation have also been reported with other biocides such as formaldehyde [26

An integrated photocatalytic/enzymatic system for the reduction of CO₂ to methanol in bioglycerol–water

• Michele Aresta,
• Angela Dibenedetto,
• Tomasz Baran,
• Antonella Angelini,
• Przemysław Łabuz and
• Wojciech Macyk

Beilstein J. Org. Chem. 2014, 10, 2556–2565, doi:10.3762/bjoc.10.267

• , namely: formate dehydrogenase (FateDH), formaldehyde dehydrogenase (FaldDH), and alcohol dehydrogenase (ADH). These enzymes promote the cascade reduction of CO2 to methanol through formic acid (FateDH), formaldehyde (FaldDH) and aldehyde (ADH). The reduction process is enabled by NADH, which is oxidized

Electrocarboxylation: towards sustainable and efficient synthesis of valuable carboxylic acids

• Roman Matthessen,
• Jan Fransaer,
• Koen Binnemans and
• Dirk E. De Vos

Beilstein J. Org. Chem. 2014, 10, 2484–2500, doi:10.3762/bjoc.10.260

• , numerous pilot scale processes have been demonstrated like the electrohydrodimerization of formaldehyde to ethylene glycol [36] or the production of glyoxylic acid [37]. The most important reasons for this raised interest are the higher energy efficiency compared to traditional thermochemical processes

Photochemical approach to functionalized benzobicyclo[3.2.1]octene structures via fused oxazoline derivatives from 4- and 5-(o-vinylstyryl)oxazoles

• Ivana Šagud,
• Simona Božić,
• Željko Marinić and
• Marija Šindler-Kulyk

Beilstein J. Org. Chem. 2014, 10, 2222–2229, doi:10.3762/bjoc.10.230

• .10.230 Abstract Novel cis/trans-4- and cis/trans-5-(2-vinylstyryl)oxazoles have been synthesized by Wittig reactions from the diphosphonium salt of α,α’-o-xylene dibromide, formaldehyde and 4- and 5-oxazolecarbaldehydes, respectively. In contrast, trans-5-(2-vinylstyryl)oxazole has been synthesized by

• /trans-Isomers of 4- and 5-oxazole derivatives (1, 2) were synthesized by Wittig reactions from the diphosphonium salt of α,α’-o-xylene dibromide, formaldehyde and oxazole-4- and 5-carbaldehydes (3, 4), respectively, in absolute ethanol with sodium ethoxide as a base (Scheme 1). The procedure of this

Pyrrolidine nucleotide analogs with a tunable conformation

• Lenka Poštová Slavětínská,
• Dominik Rejman and
• Radek Pohl

Beilstein J. Org. Chem. 2014, 10, 1967–1980, doi:10.3762/bjoc.10.205

• derivatives 7–10 were prepared from pyrrolidine azanucleosides 15a–d [5][15] via a Mannich-type reaction with diisopropyl phosphite and aqueous formaldehyde at elevated temperature in good yields (Scheme 1). The obtained diisopropyl esters 17a–d were deprotected by treatment with trimethylsilyl bromide in

Reaction of selected carbohydrate aldehydes with benzylmagnesium halides: benzyl versus o-tolyl rearrangement

• Maroš Bella,
• Bohumil Steiner,
• Vratislav Langer and
• Miroslav Koóš

Beilstein J. Org. Chem. 2014, 10, 1942–1950, doi:10.3762/bjoc.10.202

• ), produced by an addition of the Grignard reagent 10 to the monomeric formaldehyde (11, R1 = R2 = H), was unstable and decomposed by a reversible process into the Grignard reagent and aldehyde. The latter underwent a Prins-type reaction with the magnesium alkoxide intermediate E in the presence of MgCl2, to

Syntheses of ¹⁵N-labeled pre-queuosine nucleobase derivatives

• Jasmin Levic and
• Ronald Micura

Beilstein J. Org. Chem. 2014, 10, 1914–1918, doi:10.3762/bjoc.10.199

• Mannich reaction using dibenzylamine–formaldehyde and 2-acylaminopyrrolo[2,3-d]pyrimidin-4(3H)-one, which resulted in the selective introduction of the dibenzylaminomethyl group [10]. The following amine exchange reaction of the dibenzylamine function in the Mannich base with ammonia resulted in the preQ1

Multicomponent reactions in nucleoside chemistry

• Mariola Koszytkowska-Stawińska and
• Włodzimierz Buchowicz

Beilstein J. Org. Chem. 2014, 10, 1706–1732, doi:10.3762/bjoc.10.179

• as Mannich bases) can serve as starting materials in the syntheses of a variety of compounds. The employment of a nucleoside as the hydrogen active component has been one of the most common variants of the Mannich reaction. Treatment of uracil (or 2-thiouracil) nucleosides 1 with aq formaldehyde and

• involving taurine, formaldehyde and 2',3'-O-isopropylideneuridine [61]. Watanabe et al. described the synthesis of 7-(morpholinomethyl)tubercidin 5 by heating tubercidin, 37% aq formaldehyde and morpholine at 90 °C overnight (Scheme 3) [62]. Compound 5 was converted into the natural nucleoside toyocamycin

• pyrrolidine hydrochlorides 16*HCl or 20a–c*HCl (Scheme 8), Evans et al. developed a concise synthesis of 1'-aza-analogs of immucilins, compounds 19 and 21 [67]. The amine hydrochlorides were treated in aq acetate buffer with aq formaldehyde and 9-deazaguanine 18a or a variety of deazapurines 18b–e. The

Homogeneous and heterogeneous photoredox-catalyzed hydroxymethylation of ketones and keto esters: catalyst screening, chemoselectivity and dilution effects

• Axel G. Griesbeck and
• Melissa Reckenthäler

Beilstein J. Org. Chem. 2014, 10, 1143–1150, doi:10.3762/bjoc.10.114

• changes in conversion and chemoselectivity. The formation of formaldehyde as the final oxidation product was proven qualitatively (colorless precipitation of polyformaldehyde was observed in most experiments) and by a GC–MS online detection of monomeric formaldehyde. From these results, we reasoned that

• the photolysis of TiO2 in the absence of additional acceptor compounds with formation of hydrogen and eventually formation of formaldehyde [46]. Both hydrogen and formaldehyde were also detected in our experiments by gas-phase analysis. Thus, higher amounts of hydroxymethyl radicals can be produced

Site-selective covalent functionalization at interior carbon atoms and on the rim of circumtrindene, a C₃₆H₁₂ open geodesic polyarene

• Hee Yeon Cho,
• Ronald B. M. Ansems and
• Lawrence T. Scott

Beilstein J. Org. Chem. 2014, 10, 956–968, doi:10.3762/bjoc.10.94

• the great electrophilicity of circumtrindene in the Bingel–Hirsch reaction, it came as no surprise that circumtrindene can act as a good dipolarophile in a [3 + 2] cycloaddition reaction as well. Accordingly, the azomethine ylide 23 generated in situ from N-methylglycine and formaldehyde adds to

A novel family of (1-aminoalkyl)(trifluoromethyl)- and -(difluoromethyl)phosphinic acids – analogues of α-amino acids

• Natalia V. Pavlenko,
• Tatiana I. Oos,
• Yurii L. Yagupolskii,
• Igor I. Gerus,
• Uwe Doeller and
• Lothar Willms

Beilstein J. Org. Chem. 2014, 10, 722–731, doi:10.3762/bjoc.10.66

• NaHCO3, as a viscous undistillable liquid, which was stable for weeks on storage. Three-component reactions At the outset of our work three-component reactions of formaldehyde, dibenzylamine and the esters 2 or 5 were explored as model transformations to evaluate the feasibility of the Kabachnik–Fields

• formaldehyde, forming (α-hydroxymethyl)phosphinate 8. Its further irreversible rearrangement [28] to the corresponding phosphonate 9 was accompanied with hydrolysis of the ester function and formation of (trifluoromethyl)phosphonic acid (10) [29] as the main product. Analogous results were obtained, when CHF2

• . This resulted in the preparation of the analogues of glycine 14a and phenylglycine 14b (Scheme 3). The three-component reaction with formaldehyde gave the best results and N-protected aminophosphinic acid 13a was isolated in a moderate yield, alongside phosphonic acid 10. The analogous reaction with

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• secondary amines, as well as aryl and alkyl-substituted alkynes (Scheme 2). It is noteworthy that the approach tolerated challenging substrates such as formaldehyde, o-substituted benzaldehydes, and secondary aromatic amines. Moreover, the PS–NHC–Ag(I) catalyst was proven to be reusable at least 12 times

• leads to formaldehyde and ammonia, so that in the presence of silver salt the well-known silver mirror reaction could take place, thus justifying the need of at least one equiv of AgNO3. A silver supramolecular complex was proposed by Sun and co-workers as an efficient catalyst for A3-coupling reactions

• catalysis), was recently suggested by the group of Scaiano and González-Béjar [32] as a mild and green system to perform A3-MCRs. The scope was concisely explored crossing three different aldehydes (i.e., benzaldehyde, formaldehyde and 3-methylbutanal) with phenylacetylene, and three cyclic secondary amines

Simple two-step synthesis of 2,4-disubstituted pyrroles and 3,5-disubstituted pyrrole-2-carbonitriles from enones

• Murat Kucukdisli,
• Dorota Ferenc,
• Marcel Heinz,
• Christine Wiebe and
• Till Opatz

Beilstein J. Org. Chem. 2014, 10, 466–470, doi:10.3762/bjoc.10.44

• or ketones [23]. The most practical approach to a 2,4-disubstituted pyrrole reported to date is the recently disclosed microwave-assisted Stetter reaction of chalcone with carbohydrates as “green” formaldehyde equivalents followed by a microwave-assisted Paal–Knorr cyclization of the resulting 1,4

A catalyst-free multicomponent domino sequence for the diastereoselective synthesis of (E)-3-[2-arylcarbonyl-3-(arylamino)allyl]chromen-4-ones

• Pitchaimani Prasanna,
• Pethaiah Gunasekaran,
• Subbu Perumal and
• J. Carlos Menéndez

Beilstein J. Org. Chem. 2014, 10, 459–465, doi:10.3762/bjoc.10.43

• 5 were obtained in pure form in 78–94% yields (Scheme 2 and Table 2). It is noteworthy, that a similar reaction, in which the less hindered, more reactive formaldehyde was employed as the aldehyde component, took a completely divergent course and afforded 5-arylcarbonyl-1,3

• -diarylhexahydropyrimidines arising from pseudo five-component reactions of (E)-3-(dimethylamino)-1-arylprop-2-en-1-ones, two molecules of formaldehyde and two molecules of aniline [55]. The structure of compounds 5 was deduced from one and two-dimensional NMR spectroscopic data, as detailed in Supporting Information File 1

Total synthesis and cytotoxicity of the marine natural product malevamide D and a photoreactive analog

• Werner Telle,
• Gerhard Kelter,
• Heinz-Herbert Fiebig,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2014, 10, 316–322, doi:10.3762/bjoc.10.29

• phosphorochloridate), 80% over two steps, Scheme 1). N,N-Dimethylisoleucine (10), obtained by reductive dimethylation of isoleucine with aqueous formaldehyde and H2 on Pd/C [10][11], was appended at the N-terminus (DEPC, diethyl phosphorocyanidate) affording tripeptide tert-butyl ester 11. Treatment with TFA

Synthesis of new enantiopure poly(hydroxy)aminooxepanes as building blocks for multivalent carbohydrate mimetics

• Léa Bouché,
• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 213–223, doi:10.3762/bjoc.10.17

• in situ generated formaldehyde (dehydrogenation of methanol) [50][51][52][53] and subsequent aminal formation with aminooxepanes 26 and 27. The aminoalcohol 28 seems not to form the corresponding compounds. We suppose that bicyclic compound 28 is more strained and hence the formation of a third ring

Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

• Alexander O. Terent'ev,
• Dmitry A. Borisov,
• Vera A. Vil’ and
• Valery M. Dembitsky

Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6

• reaction proceeds via the formation of ozonide 73 followed by elimination of formaldehyde to give peroxycarbenium ion 74 that undergoes cyclization via the attack of the hydroperoxide group on the carbon center of peroxycarbenium ion 74 (Scheme 22) [254]. Spirohydroperoxydioxolane 75a (n = 1) was obtained