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

Indium-mediated allylation in carbohydrate synthesis: A short and efficient approach towards higher 2-acetamido-2-deoxy sugars

• Christopher Albler,
• Ralph Hollaus,
• Hanspeter Kählig and
• Walther Schmid

Beilstein J. Org. Chem. 2014, 10, 2230–2234, doi:10.3762/bjoc.10.231

• decomposition of these labile compounds. Conversion of the carbonyl moiety to an acetal group followed by treatment with azide nucleophiles also failed to yield any desired products. Therefore we decided to mask the aldehyde as an olefin. A Wittig reaction with methyl (triphenylphosphoranylidene)acetate (Ph3P

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• ozonolysis, protection of the resulting aldehyde, reduction of the lactone ring to the lactol, and treatment with methylenetriphenylphosphorane delivered 89. Mild acidic hydrolysis of the acetal followed by oxidation then yielded 90 with the γ-lactone unit that constitutes ring A of acetoxycrenulide

• primary alcohol of the side chain was oxidized with Dess–Martin periodinane (DMP) to give aldehyde 183. The latter was subsequently reacted with trimethylsilyl ketene acetal 184 in the presence of oxazaborolidinone 185 to afford aldol product 186 and the C22-epimer as only isomers in a 1:1 mixture. Dess

Synthesis of rigid p-terphenyl-linked carbohydrate mimetics

• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 1749–1758, doi:10.3762/bjoc.10.182

• °C; b) 1. THF, 2 h, −78 °C; 2. H2O, 1 h, −78 °C → rt. Synthesis of 1,2-oxazine 4 by acetal formation from 10. Conditions: a) 1-bromo-4-(dimethoxymethyl)benzene (10 equiv.), CAN, CH2Cl2, 3 d, rt. Synthesis of bicyclic ketone 11 by Lewis acid-induced rearrangement and reduction to alcohols 12a and 12b

Hindered aryl bromides for regioselective palladium-catalysed direct arylation at less favourable C5-carbon of 3-substituted thiophenes

• Rongwei Jin,
• Charles Beromeo Bheeter and
• Henri Doucet

Beilstein J. Org. Chem. 2014, 10, 1239–1245, doi:10.3762/bjoc.10.123

• than with 2-bromonitrobenzene was obtained, as 4a, 4b and 4c were formed in a 24:31:45 ratio. The use of 2-bromobenzaldehyde was not successful, as the desired product 5b was only obtained with 10% selectivity. From more hindered 2-bromobenzaldehyde diethyl acetal, the selectivity in favour of desired

4-Hydroxy-6-alkyl-2-pyrones as nucleophilic coupling partners in Mitsunobu reactions and oxa-Michael additions

• Michael J. Burns,
• Thomas O. Ronson,
• Richard J. K. Taylor and
• Ian J. S. Fairlamb

Beilstein J. Org. Chem. 2014, 10, 1159–1165, doi:10.3762/bjoc.10.116

• , entry 2), a tosylate leaving group (Table 1, entry 4), and a halide (Table 1, entry 5). Somewhat more exotic functional groups such as a phosphonate ester (Table 1, entry 6) or a dimethyl acetal (Table 1, entry 7) were still tolerated in the reaction, albeit in more modest yields. A variety of alkylated

Amino acid motifs in natural products: synthesis of O-acylated derivatives of (2S,3S)-3-hydroxyleucine

• Oliver Ries,
• Martin Büschleb,
• Markus Granitzka,
• Dietmar Stalke and
• Christian Ducho

Beilstein J. Org. Chem. 2014, 10, 1135–1142, doi:10.3762/bjoc.10.113

• to introduce an N,O-acetal moiety by transformation of 7 into the dimethyloxazolidine 8, a reaction which required careful optimization though (Scheme 2, Table 1). Using boron trifluoride and 2,2-dimethoxypropane (2,2-DiMP), as known from the synthesis of the structurally related Garner's aldehyde

• [33][34], led to an unwanted cleavage of the silyl ether and furnished a mixture of the desired product 8, the TBDMS cleavage product 9 and the corresponding O,O-acetal 10 (Table 1, entry 1). Hence, further reaction conditions using different acid catalysts and solvents were investigated. Changing the

• catalyst to pyridinium p-toluenesulfonate (PPTS) only led to small amounts of the product after prolonged reaction times and could not suppress the formation of the O,O-acetal (Table 1, entries 2 and 3). The use of racemic camphorsulfonic acid (CSA) in toluene and acetone, respectively, resulted in the

Olefin cross metathesis based de novo synthesis of a partially protected L-amicetose and a fully protected L-cinerulose derivative

• Bernd Schmidt and
• Sylvia Hauke

Beilstein J. Org. Chem. 2014, 10, 1023–1031, doi:10.3762/bjoc.10.102

• ]. With a commercial sample of Pd on charcoal (10 wt %) a plethora of products was detected, four of which could be isolated and identified as the hydrogenated acetal 11, the methyl ether 13, and the two desilylated products 14 and 15 (Table 3, entry 1). Literature precedence exists for the Pd/C-induced

• of the acetal remained a problem and the combined yield of the desired products 11 and 12 was still unsatisfactory (Table 3, entry 2). This situation changed when we used Pd(OH)2 on charcoal (10 wt %) as hydrogenation catalyst, which resulted in the exclusive formation of acetal 11 and aldehyde 12 in

• 83% combined yield (Table 3, entry 3). For the deprotection of 11 and 12 a desilylation initiated by TBAF, followed by acidic hydrolysis was investigated first. With isolated acetal 11, these conditions induced a scrambling of the benzoate and led to a mixture of the desired pyranose 16 and the

Molecular architecture with carbohydrate functionalized β-peptides adopting 3₁₄-helical conformation

• Nitin J. Pawar,
• Navdeep S. Sidhu,
• George M. Sheldrick,
• Dilip D. Dhavale and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2014, 10, 948–955, doi:10.3762/bjoc.10.93

• , galactose and xylose derivatives were incorporated as sugar units in rigid peptide templates. Keeping the proper β3-configuration for getting a β-peptide 314-helix (2–6) the isopropylidene protecting group and an anomeric acetal are structurally well tolerated. An additional perspective emerged from the

Synthesis of (2S,3R)-3-amino-2-hydroxydecanoic acid and its enantiomer: a non-proteinogenic amino acid segment of the linear pentapeptide microginin

• Rajendra S. Rohokale and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2014, 10, 667–671, doi:10.3762/bjoc.10.59

• multicomponent condensation reactions of aldehyde, an amine and ketene silyl acetal derivatives to get the vicinal hydroxylamino acids [17]. In addition, a few strategies employ a chiral pool approach. For example, Wee et al. utilized the zinc-silver-mediated reductive elimination of α-D-lyxofuranosyl