One-pot synthesis of enantiomerically pure N-protected allylic amines from N-protected α-amino esters

• Gastón Silveira-Dorta,
• Sergio J. Álvarez-Méndez,
• Víctor S. Martín and
• José M. Padrón

Beilstein J. Org. Chem. 2016, 12, 957–962, doi:10.3762/bjoc.12.94

• forming the appropriate aluminoxy acetal, which is expected to be stable enough at temperatures as low as −78 °C. This is partly corroborated by the decomposition of the aluminoxy acetal to the over reduced alcohol when 1.4 equiv of DIBAL-H were used (Table 1, entries 1, 3 and 5) [24]. The presence of an

• aluminoxy acetal is also supported when THF is used, although the yields are low, probably due to the destabilization of the aluminoxy acetal (Table 1, entry 4) [25]. Once established the reaction conditions, we next studied the scope and limitations of the one-pot protocol using a small subset of assorted

Synthesis and in vitro cytotoxicity of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine

• Štěpán Horník,
• Lucie Červenková Šťastná,
• Petra Cuřínová,
• Jan Sýkora,
• Kateřina Káňová,
• Roman Hrstka,
• Ivana Císařová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2016, 12, 750–759, doi:10.3762/bjoc.12.75

• ] of 14 followed by azidolysis [41] furnished 15. 2-Azido-3,4-epoxide 18 was prepared from readily available [42] 2,3-isopropylidene-D-mannosan (16) in five steps (Scheme 2). Tosylation of 16 [43], followed by hydrolysis of the benzylidene acetal [44] and oxirane ring closure [45] at C-4 delivered 1,6

• acetal with acetic anhydride gave a mixture containing 1,2-oxazoline 41 as the main product (Scheme 5). The structure of oxazoline 41 was confirmed by single crystal X-ray diffraction analysis which also confirmed the retention of configuration during the preceding fluorine introduction. To prevent

• to furnish acetylated 3-fluoro-GalNAc 6 isolated as a separable mixture of anomers. The D-galacto configuration of 6 is manifested by the lower 3JH3,H4 coupling value (3.4 Hz, α-anomer) in comparison with that of its C-4 epimer 5 (8.6 Hz, α-anomer). Acetolysis of the internal acetal in 26 proceeded

From steroids to aqueous supramolecular chemistry: an autobiographical career review

• Bruce C. Gibb

Beilstein J. Org. Chem. 2016, 12, 684–701, doi:10.3762/bjoc.12.69

• aromatic macrocycle [25]. Interestingly, as these hosts are tetra-acetals we initially tried removing the template under acidic conditions. However, even reflux in 1:1 EtOH/H2SO4 for a week failed to affect the starting material. Evidently, under reversible conditions, a broken acetal can easily reform

• before the other three are themselves cleaved. An irreversible acetal cleavage mechanism is therefore key to success. Meanwhile, because our chiral canyons project required some new, tripodal zinc-binding ligands for templating a collagen helix, the whole endeavor had itself become very syntheses

Three new trixane glycosides obtained from the leaves of Jungia sellowii Less. using centrifugal partition chromatography

• Luíse Azevedo,
• Larissa Faqueti,
• Marina Kritsanida,
• Antonia Efstathiou,
• Despina Smirlis,
• Gilberto C. Franchi Jr,
• Grégory Genta-Jouve,
• Sylvie Michel,
• Louis P. Sandjo,
• Raphaël Grougnet and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2016, 12, 674–683, doi:10.3762/bjoc.12.68

• oxymethine groups, the hemi-acetal and one of the CH2O (δ 3.65, 3.83/63.0) groups. Furthermore, the quaternary carbons included an α,β-unsaturated carbonyl (δ 165.5), an olefinic carbon (δ 137.5) and two sp3 carbons (δ 47.7 and 53.8). Fifteen carbon shifts remained after the sugar deduction suggesting the

Study on the synthesis of the cyclopenta[f]indole core of raputindole A

• Nils Marsch,
• Mario Kock and
• Thomas Lindel

Beilstein J. Org. Chem. 2016, 12, 334–342, doi:10.3762/bjoc.12.36

• , obtained via Au-catalyzed Meyer–Schuster rearrangement. Assembly of 5-oxygenated bisindolylpentenones. DMB: 3,4-dimethoxybenzyl, DMFDMA: N,N-dimethylformaldehyde dimethyl acetal. Benzylic oxidation as side reaction of DMB removal. Hydroxyalkylation of N-protected indoles with β-cyclocitral and SnCl4

Tandem processes promoted by a hydrogen shift in 6-arylfulvenes bearing acetalic units at ortho position: a combined experimental and computational study

• Mateo Alajarin,
• Marta Marin-Luna,
• Pilar Sanchez-Andrada and
• Angel Vidal

Beilstein J. Org. Chem. 2016, 12, 260–270, doi:10.3762/bjoc.12.28

• rate-determining one and that the [1,9]-H shift is the one with the lowest energy barrier. Keywords: acetal; benzindenes; DFT calculations; fulvene; hydrogen shift; Introduction Fulvenes (also known as pentafulvenes), [1][2][3][4] a unique class of trienes, have intrigued chemists for decades due to

• wondered whether acetalic functions could be employed as internal H donors in intramolecular hydride-like shifts, analogous to that highlighted in Scheme 1, toward fulvene frameworks. With this goal in mind we designed the unknown acetal-fulvenes 3 (Scheme 2) as potential candidates for assaying the [1,4

• Experimental study The starting acetal-fulvenes 3 were prepared by the condensation of substituted 2-(1,3-dioxolan-2-yl)benzaldehydes 4 with cyclopentadiene following a well-established synthetic methodology [33]. With the aim of promoting the desired hydride transfer by thermal activation, we first heated the

Enantioselective additions of copper acetylides to cyclic iminium and oxocarbenium ions

• Jixin Liu,
• Srimoyee Dasgupta and
• Mary P. Watson

Beilstein J. Org. Chem. 2015, 11, 2696–2706, doi:10.3762/bjoc.11.290

• alkynylations in good yields and ee’s. In 2011, we reported the first example of enantioselective alkynylation of a cyclic oxocarbenium ion intermediate (Scheme 15) [55]. Isochroman oxocarbenium ion 41 was formed in situ via Lewis acid-mediated ionization of a racemic acetal precursor. By using a Cu(MeCN)4PF6

Catalytic asymmetric formal synthesis of beraprost

• Yusuke Kobayashi,
• Ryuta Kuramoto and
• Yoshiji Takemoto

Beilstein J. Org. Chem. 2015, 11, 2654–2660, doi:10.3762/bjoc.11.285

• benzylic bromination followed by elongation of the C3 unit [22]. To this end, the ester group at the C1 position of 15 was reduced by lithium borohydride, and the resultant 1,3-diol protected to give acetal 16 [16]. After various experiments, selective bromination of the methyl group on the aromatic ring

• % yield (dr > 10:1) via the method established in Scheme 3. After derivatization to acetal 22 in 2 steps, we then turned our attention to the introduction of the C4 ester substituents. Amongst various different conditions investigated – including Pd-catalyzed coupling reactions – a halogen-lithium

Assembly of synthetic Aβ miniamyloids on polyol templates

• Sebastian Nils Fischer and
• Armin Geyer

Beilstein J. Org. Chem. 2015, 11, 2646–2653, doi:10.3762/bjoc.11.284

• example, disulfide [10], acetal [11], imine [12] and boronates [13][14][15][16], to allow the generation of new covalent structures under thermodynamic control. Complete esterification is observed for boronate esters bearing ortho-amines [17]. The conceptual advantage compared to traditional irreversible

Exploring architectures displaying multimeric presentations of a trihydroxypiperidine iminosugar

• Camilla Matassini,
• Stefania Mirabella,
• Andrea Goti,
• Inmaculada Robina,
• Antonio J. Moreno-Vargas and
• Francesca Cardona

Beilstein J. Org. Chem. 2015, 11, 2631–2640, doi:10.3762/bjoc.11.282

• , J = 12.0, 5.3 Hz, 4H, 2-Ha), 2.59 (dd, J = 11.7, 2.9 Hz, 4H, 6-Ha), 2.47–2.41 (m, 8H, 2-Hb + 6-Hb), 2.36 (t, J = 6.6 Hz, 8H, 1’-H), 2.11–2.03 (m, 8H, 2’-H), 1.49 (s, 12H, Me), 1.35 (s, 12H, Me) ppm; 13C NMR (50 MHz, CDCl3) δ 145.1 (s, 4C, C-triazole), 123.3 (d, 4C, C-triazole), 109,0 (s, 4C, acetal

• + OCH2CNH), 2.60–2.43 (m, 27H, 2-H + 1’-Ha), 2.82–2.51 (m, 27H, 6-H + 1’-Hb), 1.99–1.95 (m, 18H, 2’-H), 1.43 (s, 27H, Me), 1.35 (s, 27H, Me) ppm; 13C NMR (100 MHz, CDCl3) δ 166.5 (s, 3C, C=O), 144.4 (s, 9C, C-triazole), 135.6 (s, 3C, Ar), 128.6 (d, 3C, Ar), 123.7 (d, 9C, C-triazole), 109,0 (s, 9C, acetal

• , 1H, 2-Ha), 2.70–2.64 (m, 1H, 6-Ha), 2.51–2.43 (m, 1H, 2-Hb), 2.40–2.30 (m, 2H, 1’-H), 2.11–2.03 (m, 3H, 6-Hb + 2’-H), 1.48 (s, 3H, Me), 1.33 (s, 3H, Me) ppm; 13C NMR (100 MHz, CD3OD) δ 146.8 (s, C-triazole), 122.6 (d, C-triazole), 108.7 (s, acetal), 78.7 (d, C-4), 73.1 (d, C-3), 69.0 (d, C-5), 56.0

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• subfamilies: the xenicins (containing an 11-oxabicyclo[7.4.0]tridecane ring system with an acetal functionality) [2], the xeniolides (containing an 11-oxabicyclo[7.4.0]tridecane ring system with a lactone functionality) [3] and the xeniaphyllanes (with a bicyclo[7.2.0]undecane ring system) [4]. Later, an

• . Addition of lithium acetylide 41 to the keto group led to acetal 42. Hydrogenation of the triple bond under basic conditions resulted in cleavage of the acetal and ring closure to the corresponding lactol which was oxidized with chromic acid to furnish γ-lactone 43. An ensuing Dieckmann condensation [32

• -catalyzed and base-mediated cyclization of carbonate 71 [45]. Reductive cleavage of the sulfone using aluminium amalgam afforded a ketone, which was converted to an exocyclic double bond by treatment with Tebbe’s reagent [42]. In order to convert the methoxy acetal to the corresponding lactone, without

Continuous formation of N-chloro-N,N-dialkylamine solutions in well-mixed meso-scale flow reactors

• A. John Blacker and
• Katherine E. Jolley

Beilstein J. Org. Chem. 2015, 11, 2408–2417, doi:10.3762/bjoc.11.262

• employed in this work, with increased surface area-to-volume ratio, allows effective heat dissipation under ambient conditions. Continuous reactor A nylon/PTFE tubular reactor was constructed that incorporates static mixers for enhanced mixing of the biphasic reaction solution, made of the acetal

SmI₂-mediated dimerization of indolylbutenones and synthesis of the myxobacterial natural product indiacen B

• Nils Marsch,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2015, 11, 1700–1706, doi:10.3762/bjoc.11.184

• -Iodoindole (4) was prepared from 1-iodo-4-methyl-3-nitrobenzene (3, accessible from the corresponding nitroaniline via Sandmeyer reaction) via the Batcho–Leimgruber protocol employing dimethylformamide dimethyl acetal (DMFDMA) and TiCl3 in one step. It should be noted that, after initial column filtration of

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

• synthesis [65]. This preparation started with a Knoevenagel condensation of 2-fluoroacetophenone with malononitrile. The product of the condensation reacted with an excess of N,N-dimethylformamide dimethyl acetal to afford an enamine. This latter was treated with hydrochloric acid in acetic acid gave 4-aryl

Structure and conformational analysis of spiroketals from 6-O-methyl-9(E)-hydroxyiminoerythronolide A

• Ana Čikoš,
• Irena Ćaleta,
• Dinko Žiher,
• Mark B. Vine,
• Ivaylo J. Elenkov,
• Marko Dukši,
• Dubravka Gembarovski,
• Marina Ilijaš,
• Snježana Dragojević,
• Ivica Malnar and
• Sulejman Alihodžić

Beilstein J. Org. Chem. 2015, 11, 1447–1457, doi:10.3762/bjoc.11.157

• , with the structure and stereochemistry confirmed by X-ray crystallography. The two others were obtained during a total synthesis of erythronolide Al [55][56], as a result of deprotection of the 3,5-benzylidene acetal of erythronolide A (with or without a triethylsilyl protecting group on 6-O). However

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

A hybrid electron donor comprising cyclopentadithiophene and dithiafulvenyl for dye-sensitized solar cells

• Gleb Sorohhov,
• Chenyi Yi,
• Michael Grätzel,
• Silvio Decurtins and
• Shi-Xia Liu

Beilstein J. Org. Chem. 2015, 11, 1052–1059, doi:10.3762/bjoc.11.118

• , the synthesis of the key intermediate 7 involves the protection of one aldehyde group as an acetal using pinacol prior to HWE reaction of 5 with 4,5-bis(hexylthio)-1,3-dithiole-2-thione, followed by deprotection under acidic conditions. Aldehyde 5 was readily obtained by palladium-catalyzed Suzuki

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60

Synthesis and biological evaluation of a novel MUC1 glycopeptide conjugate vaccine candidate comprising a 4’-deoxy-4’-fluoro-Thomsen–Friedenreich epitope

• Manuel Johannes,
• Maximilian Reindl,
• Bastian Gerlitzki,
• Edgar Schmitt and
• Anja Hoffmann-Röder

Beilstein J. Org. Chem. 2015, 11, 155–161, doi:10.3762/bjoc.11.15

• ’-fluoro-TF SPPS building block 11 started by conversion of peracetylated D-glucose 1 into β-thio-glycoside 2 [45][46] under Lewis acid catalysis in 81% yield (Scheme 1). Subsequent Zemplén deacetylation [47], followed by 4,6-benzylidene acetal formation and acetylation provided fully protected precursor 3

Synthesis and characterization of pH responsive D-glucosamine based molecular gelators

• Navneet Goyal,
• Hari P. R. Mangunuru,
• Bargav Parikh,
• Sonu Shrestha and
• Guijun Wang

Beilstein J. Org. Chem. 2014, 10, 3111–3121, doi:10.3762/bjoc.10.328

• for soft biomaterials. Low molecular weight hydrogelators are especially useful for exploring biomedical applications. Previously, we found that 4,6-O-benzylidene acetal protected D-glucose and D-glucosamine are well-suited as building blocks for the construction of low molecular weight gelators. To

• better understand the scope of D-glucosamine derivatives as gelators, we synthesized and screened a novel class of N-acetylglucosamine derivatives with a p-methoxybenzylidene acetal protective group. This modification did not exert a negative influence on the gelation. On the contrary, it actually

• ]. Previously we mostly focused on the modification of the C-2 position of the benzylidene acetal protected headgroups 1 and 2 (Figure 1). We obtained the general structural requirements for acyl derivatives at the 2-position. In this study, we explore the substituent effect at the benzylidene acetal protective

Enantioselective synthesis of polyhydroxyindolizidinone and quinolizidinone derivatives from a common precursor

• Nemai Saha and
• Shital K. Chattopadhyay

Beilstein J. Org. Chem. 2014, 10, 3104–3110, doi:10.3762/bjoc.10.327

• . The O-benzylated compound 14, however, proved to be more useful in the subsequent synthetic sequence. Thus, HCl-mediated deprotection of the acetal unit in 14 resulted in simultaneous removal of the silyl protecting group leading to the triol derivative 16 in an impressive yield of 89%. One-pot

• (95% yield, Scheme 3). Repetition of the synthetic sequence on 19 detailed for the conversion 13→18, i.e., protection of the diol as its dibenzylic ether 20, acid-mediated one-pot deprotection of the acetal and silyl moieties leading to the triol 21, redox manipulation of the vicinal diol unit in the

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

Beilstein J. Org. Chem. 2014, 10, 2858–2873, doi:10.3762/bjoc.10.303

•  24 [72]. In this example, 1,2-benzoquinone derivatives are generated in the presence of ketene N,O-acetals 70. Out of four possible regioisomers, 71a and 71b are exclusively formed (in ratios 71a/71b between 1:1 and 1:2). In a follow-up study, unreacted α-arylated ketene N,O-acetal intermediates (63

Synthesis of the pentasaccharide repeating unit of the O-antigen of E. coli O117:K98:H4

• Pintu Kumar Mandal

Beilstein J. Org. Chem. 2014, 10, 2724–2728, doi:10.3762/bjoc.10.287

• reductive opening of the benzylidene acetal on treatment with sodium cyanoborohydride in the presence of HCl/Et2O [25] furnished p-methoxyphenyl 3-O-acetyl-6-O-benzyl-2-deoxy-2-phthalimido-β-D-galactopyranoside (5) in 77% yield over two steps (Scheme 1). Trisaccharide acceptor 11 could be synthesized

• % yield. NMR spectroscopy confirmed the formation of compound 8 [δ 5.04 (d, J = 3.6 Hz, 1H, H-1B), 4.38 (d, J = 7.6 Hz, 1H, H-1A) in 1H NMR and at δ 103.9 (C-1A), 100.5 (C-1B) in 13C NMR spectra]. Following an earlier report [28], cleavage of the benzylidene acetal from compound 8 catalyzed by perchloric

Galactan synthesis in a single step via oligomerization of monosaccharides

• Marius Dräger and
• Amit Basu

Beilstein J. Org. Chem. 2014, 10, 2658–2663, doi:10.3762/bjoc.10.279

• assembly is the construction of the acetal or ketal glycosidic bond that links individual sugar residues together. The synthesis of an n-mer oligosaccharide generally requires at least n−1 separate glycosylation reactions, regardless of whether the molecule is assembled in a linear or convergent manner

• by HF followed by chromatographic separation afforded chito-oligosaccharides as long as hexasaccharides in reasonable yields [13]. In most of these oligomerizations the reducing end of the oligomer is a hemi-acetal, or a reduced or protected derivative thereof, and both anomers are present [14]. An

Synthesis and immunological evaluation of protein conjugates of Neisseria meningitidis X capsular polysaccharide fragments

• Laura Morelli,
• Damiano Cancogni,
• Marta Tontini,
• Alberto Nilo,
• Sara Filippini,
• Paolo Costantino,
• Maria Rosaria Romano,
• Francesco Berti,
• Roberto Adamo and
• Luigi Lay

Beilstein J. Org. Chem. 2014, 10, 2367–2376, doi:10.3762/bjoc.10.247

• derivative very similar to 5 but protected as a 4,6-O-benzylidene acetal also led to an anomeric mixture, suggesting that conformational factors might be also involved. In addition, the treatment of this mixture with salicylchlorophosphite produced a mixture of anomeric H-phosphonates, indicating that no