An efficient synthesis of a C₁₂-higher sugar aminoalditol

• Łukasz Szyszka,
• Anna Osuch-Kwiatkowska,
• Mykhaylo A. Potopnyk and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2017, 13, 2146–2152, doi:10.3762/bjoc.13.213

• building blocks. The synthesis was realized by a regioselective introduction of the azide group and subsequent protection–deprotection transformations. The chemical reactivity of the aminoalditol was tested in the reductive amination reaction with a selectively protected sucrose monoaldehyde. Keywords

• : higher carbon sugars; reductive amination; sucrose; Introduction Carbohydrates, because of their availability in a variety of optical pure forms, are particularly useful in planning and executing the synthesis of chiral macrocyclic compounds [1][2][3][4][5]. In this context, polyhydroxylated derivatives

• ][20]. Our synthesis towards a sucrose derivative with a long alditol pendant was initiated from aldehyde 12 (readily prepared from the known [15] alcohol 11 with the free 6-OH group) and C12-aminoalditol 10 (Scheme 2). Coupling of these two species under the reductive amination conditions provided

Accessing simply-substituted 4-hydroxytetrahydroisoquinolines via Pomeranz–Fritsch–Bobbitt reaction with non-activated and moderately-activated systems

• Marco Mottinelli,
• Mathew P. Leese and
• Barry V. L. Potter

Beilstein J. Org. Chem. 2017, 13, 1871–1878, doi:10.3762/bjoc.13.182

• . Compound 18 (Scheme 7) was generated via a double reductive amination, in analogy to the syntheses of compounds 9a–q. Because none of the aromatic rings contained any activating group, the cyclization was performed with 70% HClO4 as catalyst. However, in the experimental conditions used it was not possible

• between ring formation in para- or meta-position to an activating group such as a methoxy group, when both were possible. For this, compound 22 (Scheme 8) was synthesized via a double reductive amination, as per synthesis of 9a–q. As expected, when the precursor was treated with 6 M HCl, the cyclization

• procedures were followed unless indicated otherwise. Some representative examples of spectroscopic data are reported below. The complete sets of data are reported in Supporting Information File 1. General method for the double reductive amination reaction NaBH(OAc)3 (3.3 g, 15 mmol) was added to a stirring

Aqueous semisynthesis of C-glycoside glycamines from agarose

• Juliana C. Cunico Dallagnol,
• Alexandre Orsato,
• Diogo R. B. Ducatti,
• Miguel D. Noseda,
• Maria Eugênia R. Duarte and
• Alan G. Gonçalves

Beilstein J. Org. Chem. 2017, 13, 1222–1229, doi:10.3762/bjoc.13.121

• starting material to produce primary, secondary and tertiary C-glycoside glycamines, including mono- and disaccharide structures. The semisynthetic approach utilized was generally based on polysaccharide-controlled hydrolysis followed by reductive amination. All reactions were conducted in aqueous media

• and without the need of hydroxyl group protection. We were able to identify optimal conditions for the reductive amination of agar hydrolysis products and to overcome the major difficulties related to this kind of reaction, also extending it to reducing anhydrosugars. The excess of ammonium acetate

• , methyl- or dimethylamine, and the use of a diluted basic (pH 11) reaction media were identified as important aspects to achieve improved yields, as well as to decrease the amount of byproducts commonly related to reductive amination of carbohydrates. This strategy allowed the transposition of the 3,6

Automating multistep flow synthesis: approach and challenges in integrating chemistry, machines and logic

• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2017, 13, 960–987, doi:10.3762/bjoc.13.97

Exploring endoperoxides as a new entry for the synthesis of branched azasugars

• Svenja Domeyer,
• Mark Bjerregaard,
• Henrik Johansson and
• Daniel Sejer Pedersen

Beilstein J. Org. Chem. 2017, 13, 644–647, doi:10.3762/bjoc.13.63

• ready access to the two lactol isomers 29,30 in quantitative yield (≈1:1 ratio of isomers) [10][22][23]. Lactol isomers 29,30 could potentially serve as precursors for the formation of substituted piperidines via reductive amination or be oxidised to yield lactones or lactam derivatives. Conclusion

Continuous N-alkylation reactions of amino alcohols using γ-Al₂O₃ and supercritical CO₂: unexpected formation of cyclic ureas and urethanes by reaction with CO₂

• Emilia S. Streng,
• Darren S. Lee,
• Michael W. George and
• Martyn Poliakoff

Beilstein J. Org. Chem. 2017, 13, 329–337, doi:10.3762/bjoc.13.36

• ., boron salts from reductive amination [4]. Hydrogenation offers a greener approach but is often only applicable to simple substrates due to chemoselectivity issues. An approach that has received much attention recently is the concept of hydrogen borrowing catalysis [5][6][7][8][9][10][11][12][13][14][15

First DMAP-mediated direct conversion of Morita–Baylis–Hillman alcohols into γ-ketoallylphosphonates: Synthesis of γ-aminoallylphosphonates

• Marwa Ayadi,
• Haitham Elleuch,
• Emmanuel Vrancken and
• Farhat Rezgui

Beilstein J. Org. Chem. 2016, 12, 2906–2915, doi:10.3762/bjoc.12.290

• were prepared by reductive amination of γ-aminophosphonyl ketones using sodium borohydride [41], or by conjugate addition of diethyl methylphosphonite to 2-cyclohexenone followed by Bucherer–Bergs amino acid synthesis [42]. Another synthetic approach for a series of α-fluorinated-γ-aminophosphonates

Experimental and theoretical investigations into the stability of cyclic aminals

• Edgar Sawatzky,
• Antonios Drakopoulos,
• Martin Rölz,
• Christoph Sotriffer,
• Bernd Engels and
• Michael Decker

Beilstein J. Org. Chem. 2016, 12, 2280–2292, doi:10.3762/bjoc.12.221

• tetrahydroquinazoline core (Scheme 4b). Thus, anthranilic acid was alkylated by reductive amination with acetone and NaBH4 in two steps to yield the isopropyl-substituted derivative 14. The derivative 14 and the commercially available N-phenylanthranilic acid were converted to amides 15a,b under standard conditions

DNA functionalization by dynamic chemistry

• Zeynep Kanlidere,
• Oleg Jochim,
• Marta Cal and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2016, 12, 2136–2144, doi:10.3762/bjoc.12.203

• containing ON1 and four nucleobases in the presence of a DNA-template: a) TC; b) TG; c) TT; d) TA. The chromatograms were performed after reductive amination of the samples (for more details see Supporting Information File 1). Representative HPLC chromatograms obtained using elevated pH, for samples

• collected from first purification step (in Figure 4 marked with dashed line). The samples were collected from the reaction of ON1 and four nucleobases in the presence of a DNA-template: a) TC; b) TG; c) TT; d) TA. The chromatograms were obtained after reductive amination of the samples (for more details see

A chiral analog of the bicyclic guanidine TBD: synthesis, structure and Brønsted base catalysis

• Mariano Goldberg,
• Denis Sartakov,
• Jan W. Bats,
• Michael Bolte and
• Michael W. Göbel

Beilstein J. Org. Chem. 2016, 12, 1870–1876, doi:10.3762/bjoc.12.176

• -von-Laue-Straße 7, D-60438 Frankfurt am Main, Germany 10.3762/bjoc.12.176 Abstract Starting from (S)-β-phenylalanine, easily accessible by lipase-catalyzed kinetic resolution, a chiral triamine was assembled by a reductive amination and finally cyclized to form the title compound 10. In the crystals

• reductive amination to form 18 (58%). After removal of the Boc protecting group (quant.), triamine 19 was reacted with dimethyl trithiocarbonate in refluxing nitromethane. The thiourea intermediate was activated in situ by S-alkylation with MeI. Upon further heating the final cyclization occured forming the

Practical synthetic strategies towards lipophilic 6-iodotetrahydroquinolines and -dihydroquinolines

• David R. Chisholm,
• Garr-Layy Zhou,
• Ehmke Pohl,
• Roy Valentine and
• Andrew Whiting

Beilstein J. Org. Chem. 2016, 12, 1851–1862, doi:10.3762/bjoc.12.174

• avoid. However, the desired product 6 can be isolated using basic alumina chromatography. Reductive amination with acetone, mediated by AcOH and NaOAc was also pursued as an alternative strategy [18]. While being much easier to purify due to the elimination of the bis-alkylation product, the yield of

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• separated by column chromatography. After debenzylation, the resultant primary amines were connected with amido aldehydes 6 substituted with different moieties R and R' by reductive amination with R being either a hydroxy group or a hydrogen and R' representing an alkyl, allyl, ester or a protected amino

• followed by an azide reduction, Boc protection, saponification of the ester, peptide coupling with the amino acid 17, oxidative cleavage of the double bond to give 18 and an intramolecular reductive amination in order to construct the seven-membered ring. Methylation with subsequent acidic global

• diastereoselectively converted with a Grignard reagent into the amine 53 as a key step of the synthesis [78]. Cbz protection followed by ozonolysis with subsequent reductive amination and hydrogenolysis led to the 1,3-diamine 54. The cyclisation to the guanidine functionality was achieved with the novel

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• desired products in excellent yields and selectivities. In order to broaden the utility of this methodology, the authors reduced the nitro group to an amine. The product was in situ transformed to the tricyclic product 102, through a diastereoselective reductive amination, that controlled the

A novel and practical asymmetric synthesis of dapoxetine hydrochloride

• Yijun Zhu,
• Zhenren Liu,
• Hongyan Li,
• Deyong Ye and
• Weicheng Zhou

Beilstein J. Org. Chem. 2015, 11, 2641–2645, doi:10.3762/bjoc.11.283

• temperature and dissociated with NaHCO3 to give the primary amine 6 in 90.0% yield. The reductive amination of 6 under Eschweiler–Clarke conditions furnished (S)-dapoxetine 7 with excellent enantiopurity (99.3% ee) in 74.7% yield. After salt formation and recrystallization, the target compound 1 was obtained

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

• strategy for the synthesis of diversely functionalized trihydroxypiperidines through double reductive amination of the D-mannose-derived aldehyde 2 (Scheme 1) [24][25]. Among the 1-azasugars accessed with this methodology, our attention was drawn to the enantiomer of natural 3,4,5-trihydroxypiperidine (1

• [24][33]. The versatility of our synthetic methodology allows access to differently substituted N-alkylated trihydroxypiperidines by simply using the same aldehyde and different amines as the nitrogen source in a double reductive amination strategy [24][25]. In particular, catalytic hydrogenation with

• Pd(OH)2/C in MeOH followed by reductive amination of the formed dialdehyde intermediate with 3-azidopropyl-1-amine [34] in the presence of NaBH3CN and AcOH allowed access to N-alkylated piperidine 4 in 67% yield (Scheme 2) [25]. With the key azido intermediate 4 in hands, we proceeded with the

Fates of imine intermediates in radical cyclizations of N-sulfonylindoles and ene-sulfonamides

• Hanmo Zhang,
• E. Ben Hay,
• Stephen J. Geib and
• Dennis P. Curran

Beilstein J. Org. Chem. 2015, 11, 1649–1655, doi:10.3762/bjoc.11.181

• amination of N-tosylindole aldehyde 6 with 2-iodoaniline (66%), followed by methylation of the aniline nitrogen atom (91%). Substrate 10 with the ester on C2 of the indole was chosen to learn if a more stabilized radical intermediate would still eliminate the N-tosyl group. Reductive amination of 9, 2

• cyclization indeed undergoes elimination to form an imine, but that this cyclic imine is directly reduced by tributyltin hydride by either a radical or ionic pathway. We next studied two aryl radical cyclizations of N-sulfonylindoles, as shown in Scheme 2. Substrate 7 was made in two steps by reductive

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

• , reduction with LiAlH4, reductive amination and allylation that afforded the indole derivatives 63 (18%) and N-Boc protected compound 68 (23%). The reaction of 63 with Pd(OAc)2 (25 mol %) and tri(o-tolyl)phosphine (55 mol %) at reflux gave 9-endo-64a (24%) and 8-exo-65b (21%). However, the compound 68 under

Discrete multiporphyrin pseudorotaxane assemblies from di- and tetravalent porphyrin building blocks

• Mirko Lohse,
• Larissa K. S. von Krbek,
• Sebastian Radunz,
• Suresh Moorthy,
• Christoph A. Schalley and
• Stefan Hecht

Beilstein J. Org. Chem. 2015, 11, 748–762, doi:10.3762/bjoc.11.85

• obtained through the condensation of aldehyde 3 with mesityldipyrromethane (6) followed by metalation of the intermediately formed free base porphyrin 7 to give its respective zinc complex 2. In the next step, axle precursor 8 was synthesized by reductive amination of 4-bromobenzaldehyde (9) and

Synthesis of multivalent carbohydrate mimetics with aminopolyol end groups and their evaluation as L-selectin inhibitors

• Joana Salta,
• Jens Dernedde and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2015, 11, 638–646, doi:10.3762/bjoc.11.72

• hence compounds inhibiting their activity are of interest as potential therapeutics [19][20][21][22][23]. In a previous report [24] we described the synthesis of divalent carbohydrate mimetics connecting aminopyran 1 or its simplified analog serinol (2) (Scheme 1) to different linker units by reductive

• amination of aldehydes. We now enclose our results on the preparation of related di- and trivalent carbohydrate mimetics in which compounds 1 or 2 are connected to carboxylic acid cores by amide bonds. A series of compounds with spacer units of different length and rigidity were prepared in order to find

Hydrogenation of unactivated enamines to tertiary amines: rhodium complexes of fluorinated phosphines give marked improvements in catalytic activity

• Sergey Tin,
• Tamara Fanjul and
• Matthew L. Clarke

Beilstein J. Org. Chem. 2015, 11, 622–627, doi:10.3762/bjoc.11.70

• out as reductive amination or reduction of enamines need stoichiometric acetic acid to promote the formation of the iminium ion that is the substrate reduced in hydride reductions, which might not be compatible with other functional groups. To the best of our knowledge, the hydrogenation of

Stereoselective cathodic synthesis of 8-substituted (1R,3R,4S)-menthylamines

• Carolin Edinger,
• Jörn Kulisch and
• Siegfried R. Waldvogel

Beilstein J. Org. Chem. 2015, 11, 294–301, doi:10.3762/bjoc.11.34

• naturally occurring terpenoids is the reductive amination under Leuckart–Wallach conditions (see Scheme 2, pathway I) [39]. This method was applied to convert 2 to N-alkyl substituted menthylamines [40]. However, a significant disadvantage of this method is the lack of stereocontrol and partial inversion of

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

Conjugates of methylated cyclodextrin derivatives and hydroxyethyl starch (HES): Synthesis, cytotoxicity and inclusion of anaesthetic actives

• Lisa Markenstein,
• Antje Appelt-Menzel,
• Marco Metzger and
• Gerhard Wenz

Beilstein J. Org. Chem. 2014, 10, 3087–3096, doi:10.3762/bjoc.10.325

• known to have a much lower toxic potential compared to CD monomers [20]. Native β-CD was already conjugated by esterification [21], reductive amination [22][23][24][25], amide coupling [26][27] and [2 + 3] cycloadditions [28] to both biogenic and synthetic polymers. Conjugation of CDs to polysaccharides

Bifunctional dendrons for multiple carbohydrate presentation via carbonyl chemistry

• Davide Bini,
• Francesco Nicotra and
• Laura Cipolla

Beilstein J. Org. Chem. 2014, 10, 1686–1691, doi:10.3762/bjoc.10.177

• carbonyl group at the termini has been carried out. The carbonyl group has been exploited for the multivalent conjugation to a sample saccharide by reductive amination and alkoxyamine conjugation. Keywords: bis-MPA; carbohydrates; dendrons; levulinic acid; multivalency; multivalent glycosystems

• carbonyl groups can be exploited for carbohydrate functionalization [15][16] by reductive amination, oxime or hydrazone formation to yield suitably functionalized saccharides (Figure 1). Given the relevance of L-fucose in mammal oligosaccharides, α-L-(2-aminoethyl) fucoside [17] and α-O-L

• synthesized from commercial L-fucopyranose in 4 and 5 steps, respectively, as already reported by Flitsch and co-workers [17] and Dumy and co-workers [18]. Dendron conjugation to L-fucose by reductive amination α-L-(2-Aminoethyl) fucopyranoside (4) was conjugated first to G0 dendron 1 by reductive amination

Carbohydrate PEGylation, an approach to improve pharmacological potency

• M. Eugenia Giorgi,
• Rosalía Agusti and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2014, 10, 1433–1444, doi:10.3762/bjoc.10.147

• mannose to PEI via a PEG chain spacer (Figure 3B). This system was used to deliver small interfering RNA (siRNA) into a murine macrophage cell line [44]. Mannose residues as their 2-aminoethyl glycosides were attached by reductive amination to the surface of copolymer micelles of PEG with poly-ε