Synthesis of 5-oxyquinoline derivatives for reversal of multidrug resistance

• Torsten Dittrich,
• Nils Hanekop,
• Nacera Infed,
• Lutz Schmitt and
• Manfred Braun

Beilstein J. Org. Chem. 2012, 8, 1700–1704, doi:10.3762/bjoc.8.193

• better for Pdr5. Keywords: acetals; enantiopure compounds; heterocycles; inhibitor; multidrug resistance; Introduction The treatment of cancer is often severely hampered by efflux pumps, which are responsible for the extrusion of various chemotherapeutics from the tumor cell, an effect termed

• of the stereogenic carbinol center. Thus, we replaced the piperazine motif in 1 by a piperidine ring carrying either nitrogen or oxygen as a hetero substituent(s) in the 4-position. Therefore, an initial series of 4-aminopiperidines 2a–4a and, in a second approach, new spirocyclic acetals 5a–12a as

• well as the thioacetal 13a were synthesized. All the new compounds, shown in Scheme 1, were obtained in enantiomerically pure form, with the stereogenic carbinol center adopting (R) configuration. The acetals 8a and 9a formed as mixtures of diastereomers, whereas compound 10a was enantiomerically and

The Amadori rearrangement as glycoconjugation method: Synthesis of non-natural C-glycosyl type glycoconjugates

• Katharina Gallas,
• Gerit Pototschnig,
• Florian Adanitsch,
• Arnold E. Stütz and
• Tanja M. Wrodnigg

Beilstein J. Org. Chem. 2012, 8, 1619–1629, doi:10.3762/bjoc.8.185

• corresponding acetals when the pH value is kept below 6 [30]. In the D-gluco series, D-glycero-D-gulo-aldoheptose 10 was isolated in 81% yield, and no C-2 epimer was detected, as shown by comparison of the NMR data with a commercial sample [31]. Aldoheptose 10 was taken to the Amadori rearrangement without

Organocatalytic C–H activation reactions

• Subhas Chandra Pan

Beilstein J. Org. Chem. 2012, 8, 1374–1384, doi:10.3762/bjoc.8.159

• , ether and acetals delivering the products 7 in good to excellent yields (50–94%). The reaction was also compatible with different ketones although extended reaction times were required to obtain good yields of the desired products. Interestingly, when the substrates were extended to five and six

Synthesis of fluorinated maltose derivatives for monitoring protein interaction by ¹⁹F NMR

• Michaela Braitsch,
• Hanspeter Kählig,
• Georg Kontaxis,
• Michael Fischer,
• Toshinari Kawada,
• Robert Konrat and
• Walther Schmid

Beilstein J. Org. Chem. 2012, 8, 448–455, doi:10.3762/bjoc.8.51

• regioselective reductive ring opening of benzylidene acetals in the maltose derivative 11 was performed with a complex of BH3/Bu2BOTf at −70 °C [32][33]. Fluorination with DAST [34][35] was performed in a sealed tube for 1 h at 80 °C under microwave conditions. The deprotection of the benzyl group was achieved

Acceptor-influenced and donor-tuned base-promoted glycosylation

• Stephan Boettcher,
• Martin Matwiejuk and
• Joachim Thiem

Beilstein J. Org. Chem. 2012, 8, 413–420, doi:10.3762/bjoc.8.46

• yields of up to 95%. Preparation of the 3-O-monobenzylated methyl α- and β-D-galactopyranosyl acceptors 5 and 6 was achieved via stannylidene acetals [6] (Scheme 2). Compound 18 was subjected to a one-step synthesis with Bu2SnO and BnBr, affording target compound 5. The synthetic route for the methyl β

Recent advances in the gold-catalyzed additions to C–C multiple bonds

• He Huang,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2011, 7, 897–936, doi:10.3762/bjoc.7.103

• benzobicyclo[5.3.1]acetals 87 were produced when triazole–gold was employed as the catalyst. With alcohol nucleophiles, gold(I)-catalyzed cyclization of o-alkynyl benzaldehyde 88 and benzaldimine–chromium complexes gave stereoselectively 1-anti-functionalized heterocycle chromium complexes 89 (Scheme 16) [47

Synthesis of novel 5-alkyl/aryl/heteroaryl substituted diethyl 3,4-dihydro-2H-pyrrole-4,4-dicarboxylates by aziridine ring expansion of 2-[(aziridin-1-yl)-1-alkyl/aryl/heteroaryl-methylene]malonic acid diethyl esters

• Satish S. More,
• T. Krishna Mohan,
• Y. Sateesh Kumar,
• U. K. Syam Kumar and
• Navin B. Patel

Beilstein J. Org. Chem. 2011, 7, 831–838, doi:10.3762/bjoc.7.95

• reactions led to various by-products probably as a result of protonation and dehydrohalogenation of the presumed intermediates [28] (Scheme 1). Junjappa and co-workers were successful in iodide ion mediated ring expansion of N-vinylaziridine N,S-acetals containing cyano- and ester groups on the β-carbon and

When cyclopropenes meet gold catalysts

• Frédéric Miege,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2011, 7, 717–734, doi:10.3762/bjoc.7.82

• determination of the cationic or carbenic nature of organogold intermediates, but the presence of the two oxygen atoms in cyclopropenone acetals unavoidably led to more favorable cationic forms and hence cannot provide a general answer. Using the M06 functional of DFT, Toste et al. calculated rotational

• by ring-opening of 3 should instead react as a gold-stabilized carbocation due to the presence of oxygen atoms that can stabilize the cationic intermediate. However, it is worth pointing out that Boger and Brotherton previously reported that cyclopropenone acetals could cyclopropanate electron

• new possibilities and further synthetic developments in this field will certainly be reported. General reactivity of cyclopropenes in the presence of gold catalysts. Cationic organogold species generated from cyclopropenone acetals. Rotation barriers around the C2–C3 bond (M06 DFT calculations). Au–C1

Synthesis, reactivity and biological activity of 5-alkoxymethyluracil analogues

• Lucie Brulikova and
• Jan Hlavac

Beilstein J. Org. Chem. 2011, 7, 678–698, doi:10.3762/bjoc.7.80

• )pyrimidines 68 and 69. The latter readily underwent nucleophilic attack by alkoxide ions to yield alicyclic or cyclic acetals 70–73 and 74, respectively, depending on the alcohol used. Uridine and arabinofuranosyl analogues: 5-Substituted uracil nucleosides where the sugar component is ribose or arabinose

Gold-catalyzed heterocyclizations in alkynyl- and allenyl-β-lactams

• Benito Alcaide and
• Pedro Almendros

Beilstein J. Org. Chem. 2011, 7, 622–630, doi:10.3762/bjoc.7.73

• . Deauration and proton transfer leads to adduct 27 with concomitant regeneration of the Au(III) species (Scheme 15). Regiocontrolled gold/Brønsted acid co-catalyzed direct bis-heterocyclization of alkynyl-β-lactams allows the efficient synthesis of optically pure tricyclic bridged acetals bearing a 2

• . Possible catalytic cycle for the gold-catalyzed cyclization of MOM protected alkynol derivatives. Gold/Brønsted acid co-catalyzed formation of bridged β-lactam acetals from 2-azetidinone-tethered alkynyl dioxolanes. Acknowledgements Support for this work by the MICINN (Project CTQ2009-09318), Comunidad

Synthesis of glycoconjugate fragments of mycobacterial phosphatidylinositol mannosides and lipomannan

• Benjamin Cao,
• Jonathan M. White and
• Spencer J. Williams

Beilstein J. Org. Chem. 2011, 7, 369–377, doi:10.3762/bjoc.7.47

• reductively-removed protecting groups such as benzyl ethers must be avoided owing to their incompatibility with the azido group when using H2/Pd or Na/NH3. We therefore sought to develop a synthesis based on the use of esters, silyl ethers and acetals only. Synthesis of monosaccharide building blocks

Approaches towards the synthesis of 5-aminopyrazoles

• Ranjana Aggarwal,
• Vinod Kumar,
• Rajiv Kumar and
• Shiv P. Singh

Beilstein J. Org. Chem. 2011, 7, 179–197, doi:10.3762/bjoc.7.25

• corresponding 5-amino-3-arylamino-1-phenylpyrazole-4-carboxamides 90 (Scheme 25) [67]. Ketene S,S- and S,N-acetals or tetracyanoethylene 91 on reaction with 3-hydrazino-6-(p-tolyl)pyridazine afforded the 5-amino-4-cyanopyrazoles 92 (Scheme 26) [68]. Several thiazolylpyrazoles 97–100 bearing a variety of

Heavy atom effects in the Paternò–Büchi reaction of pyrimidine derivatives with 4,4’-disubstituted benzophenones

• Feng-Feng Kong,
• Jian-Bo Wang and
• Qin-Hua Song

Beilstein J. Org. Chem. 2011, 7, 113–118, doi:10.3762/bjoc.7.16

• Paternò–Büchi reaction, spin-transition processes would be affected, and this may lead to interesting results. Abe et al. [14] investigated the effect of a sulfur atom on the stereoselective formation of oxetanes in Paternò–Büchi reaction of aromatic aldehydes with silyl O,S-ketene acetals to give trans-3

Synthesis of 2a,8b-Dihydrocyclobuta[a]naphthalene-3,4-diones

• Kerstin Schmidt and
• Paul Margaretha

Beilstein J. Org. Chem. 2010, 6, No. 76, doi:10.3762/bjoc.6.76

• . In the same experiment with 1c, the MeO-group apparently tends to increase the efficiency in photodimerization vs mixed photocycloaddition, otherwise there is no obvious explanation for this result. Experimental 1. General. Acetals 1 were synthesized according to [8]. Both 1b, m.p. 60–62 °C, and 1c

Acid catalyzed cyclodimerization of 2,2-bis(trifluoromethyl)-4-alkoxy-oxetanes and -thietanes. Synthesis of 2,2,6,6-tetrakis(trifluoromethyl)-4,8-dialkoxy-1,5-dioxocanes and 3,3,7,7-tetrakis(trifluoromethyl)-9-oxa-2,6-dithia-bicyclo[3.3.1]nonane

• Viacheslav A. Petrov and
• Will Marshall

Beilstein J. Org. Chem. 2010, 6, No. 46, doi:10.3762/bjoc.6.46

• products. Clean and spontaneous reaction with alcohols is another interesting transformation of oxetanes described in this paper. The reaction leads to high yield formation of the corresponding acetals (CF3)2C(OH)CH2CH(OR)OR′. Structurally related 2,2-bis(trifluoromethyl)-4-R-thietanes (R = i-C3H7O, t

• alcohols in the absence of the catalyst. The reaction leads to a ring opening with the formation of the corresponding acetals of 4,4,4-trifluoro-3-(trifluoromethyl)-3-hydroxybutanal. For example, the addition of 1b or 1c to an excess of methanol results in a fast and mildly exothermic reaction, leading to

• selective formation of acetals 3a or 3b, respectively (Scheme 3). Since the vacuum distillation of 3b lead to decomposition, the isolation of similar products in an analytically pure form was not attempted. However, removal of excess alcohol after the reaction was complete by washing with water afforded

Fused bicyclic piperidines and dihydropyridines by dearomatising cyclisation of the enolates of nicotinyl-substituted esters and ketones

• Heloise Brice,
• Jonathan Clayden and
• Stuart D. Hamilton

Beilstein J. Org. Chem. 2010, 6, No. 22, doi:10.3762/bjoc.6.22

• it into a silyl enol ether 9. Silyl enol ethers and ketene acetals are known to add effectively to pyridinium species in an intermolecular manner [42][43][44][45][46]. Thus 7 was converted to silyl enol ether 9 in excellent yield under standard conditions. A single geometrical isomer was obtained

• chloroformate to activate the pyridine without competing attack by the enolate. Next we extended the reaction to the cyclisation of a δ-nicotinyl butyrate ester 12 encouraged by the observations of Onaka [47], who demonstrated that silyl ketene acetals can be added (in an intermolecular fashion) to electron

A review of new developments in the Friedel–Crafts alkylation – From green chemistry to asymmetric catalysis

• Magnus Rueping and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2010, 6, No. 6, doi:10.3762/bjoc.6.6

• arenecarbaldehydes and their corresponding acetals have been used as electrophilic component [7]. While FC alkylations with allyl alcohols and benzyl ethers are likely to have the same carbocationic reaction intermediate, the FC alkylation with arenecarbaldehydes 6 has to be different (Scheme 5). Mechanistic

Synthesis of mesogenic phthalocyanine-C₆₀ donor–acceptor dyads designed for molecular heterojunction photovoltaic devices

• Yves Henri Geerts,
• Olivier Debever,
• Claire Amato and
• Sergey Sergeyev

Beilstein J. Org. Chem. 2009, 5, No. 49, doi:10.3762/bjoc.5.49

• , attempted condensation of 5 and 6a–d gave no desired phthalocyanine derivative. We reasoned that the unprotected OH group in one of the reaction components may affect the condensation, and converted alcohols 6a–d into acetals 9a–d (84–93% yield) by treatment with an excess of methoxyethoxymethyl chloride

2-Phenyl- tetrahydropyrimidine- 4(1H)-ones – cyclic benzaldehyde aminals as precursors for functionalised β²-amino acids

• Markus Nahrwold,
• Arvydas Stončius,
• Anna Penner,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2009, 5, No. 43, doi:10.3762/bjoc.5.43

• . In the course of this study, an L-asparagine derivative was condensed with benzaldehyde and subsequently converted to orthogonally protected (R)-β2-homoaspartate. Keywords: β2-amino acids; cyclocondensation; diastereoselective alkylation; N,N-acetals; peptidomimetics; ring opening; self-regeneration

• compounds 11b/13. The decisive influence of N-acyl substituents within cyclic five- and six-membered N,N-and N,O-acetals on the stereochemical course of alkylations and ring closure reactions is a long known and frequently observed phenomenon (for an overview, see ref. [50]). The at first sight surprising

• , this novel concept was applied to synthesise orthogonally protected (R)-β2-homoaspartate by means of “self-regeneration of stereogenic centres” (SRS). Asparagine derived benzaldehyde N,N-acetals comparable to 9 have formerly been used as α-alkyl-asparagine precursors [39] and furthermore have been

Acid- mediated reactions under microfluidic conditions: A new strategy for practical synthesis of biofunctional natural products

• Katsunori Tanaka and
• Koichi Fukase

Beilstein J. Org. Chem. 2009, 5, No. 40, doi:10.3762/bjoc.5.40

• important synthetic intermediate for complex N-glycans. Microfluidic reductive opening of sugar 4,6-O-benzylidene acetals The microfluidic conditions can also be applied to an efficient procedure for the reductive opening of 4,6-O-benzylidene acetals [30], a key functional group manipulation toward fragment

• b for our N-glycan synthesis. Reductive opening of sugar 4,6-O-benzylidene acetals by the combination of acid/hydride reagents is one of the most useful transformations in the field of carbohydrate chemistry [49], not only for our current N-glycan case, since the benzyl-protected derivatives at

• either the C4- or C6-hydroxyl can be selectively prepared by the choice of reagent and/or solvent systems [50][51]. The typical procedure of the reductive opening of the acetals involves the very slow addition of the acid to a mixture of the substrate and excess hydride reagent at 0 °C, followed by

Catalytic synthesis of (E)-α,β-unsaturated esters from aldehydes and 1,1-diethoxyethylene

• Rubén Manzano,
• Lidia Ozores,
• Andreas Job,
• Lars Rodefeld and
• Benjamin List

Beilstein J. Org. Chem. 2009, 5, No. 3, doi:10.3762/bjoc.5.3

• treatment with a suitable reagent or catalyst could readily lead to the corresponding unsaturated ester and ethanol or methanol as the only by-product. The use of ketene dialkyl acetals for organic transformations is infrequent [27]. To the best of our knowledge, they have been employed in [2+2

Diels- Alder reactions using 4,7-dioxygenated indanones as dienophiles for regioselective construction of oxygenated 2,3-dihydrobenz[f]indenone skeleton

• Natsuno Etomi,
• Takuya Kumamoto,
• Waka Nakanishi and
• Tsutomu Ishikawa

Beilstein J. Org. Chem. 2008, 4, No. 15, doi:10.3762/bjoc.4.15

• -opened product 27. Transition states supposed for the regioselective DAR via quinone route. Representative LUMO coeffients of quinones 8 and 12 (a) and their reaction courses with diene 7 (b). Retrosynthesis of kinamycins. Synthesis of quinones 8 and 12 and the acetals 13 and 14. Reagents and conditions

A divergent asymmetric approach to aza-spiropyran derivative and (1S,8aR)-1-hydroxyindolizidine

• Jian-Feng Zheng,
• Wen Chen,
• Su-Yu Huang,
• Jian-Liang Ye and
• Pei-Qiang Huang

Beilstein J. Org. Chem. 2007, 3, No. 41, doi:10.1186/1860-5397-3-41

• to N,O-dibenzyl malimide (4) leads to N,O-acetals 5 in high regioselectivity (Scheme 2), and the subsequent reductive dehydroxylation gives 6 in high trans-diastereoselectivity.[35] On the other hand, treatment of N,O-acteals 5 with an acid furnished enamides E, which can be transformed

• findings are surprising comparing with our recent observations. In our previous investigations, it was observed that the treatment of N,O-acetals 5 with an acid leads to the dehydration products E (Scheme 2), and the two diastereomers of 5 shows different reactivities towards the acid-promoted dehydration

Aroylketene dithioacetal chemistry: facile synthesis of 4-aroyl- 3-methylsulfanyl- 2-tosylpyrroles from aroylketene dithioacetals and TosMIC

• H. Surya Prakash Rao and
• S. Sivakumar

Beilstein J. Org. Chem. 2007, 3, No. 31, doi:10.1186/1860-5397-3-31

• heterocyclic systems, examples of their participation in the cycloaddition reactions are rare. In continuation of our interest on ketene acetals [5][6][7] we considered that 1,3-dipolar cycloaddition of the anion generated from the von Leusen's reagent (p-tolylsulfonyl)methyl isocyanide (TosMIC) 2 to AKDTAs 1

The use of silicon- based tethers for the Pauson- Khand reaction

• Adrian P. Dobbs,
• Ian J. Miller and
• Saša Martinović

Beilstein J. Org. Chem. 2007, 3, No. 21, doi:10.1186/1860-5397-3-21

• , the acyclic silicon containing chains are simple to synthesise, such as through the formation of either silyl ethers or acetals, may contain a wide range of functionalities and are stable to a range of different reaction conditions and purification techniques. Second, the silicon tethers remain inert

• standard P-K reaction conditions. Analysis of the reaction solution showed that cyclisation had not occurred and the only compound recovered was a quantitative amount of the starting material. ii) Silyl acetal tethers Although silyl ethers have been the predominant ether of choice, silyl acetals have been

• applied as temporary tethers in reactions.[32] Silyl acetals have, for example, been applied to any reactions to which silyl ether have been applied, such as radical, Diels Alder reaction or ring closing metathesis, albeit with varying degrees of success. The advantage of silyl acetals over silyl ethers