The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

• which although commercially available was expensive and could be generated from 1,3-cyclohexadione (104). The sequence consisted of O-acetylation, a Steglich rearrangement, oxidation and a final methylation reaction. As the use of flow chemistry had already improved the O-acetylation during scale-up

Gold-catalyzed formation of pyrrolo- and indolo-oxazin-1-one derivatives: The key structure of some marine natural products

• Sultan Taskaya,
• Nurettin Menges and
• Metin Balci

Beilstein J. Org. Chem. 2015, 11, 897–905, doi:10.3762/bjoc.11.101

• ]. Results and Discussion The starting compound 11 was synthesized via a slightly modified route by acetylation of pyrrole with trichloroacetyl chloride in 99% yield [42][43]. The propargyl ester 13 [44][45][46] was obtained in high yield from the reaction of 12 with propargyl bromide in the presence of NaH

DNA display of glycoconjugates to emulate oligomeric interactions of glycans

• Alexandre Novoa and
• Nicolas Winssinger

Beilstein J. Org. Chem. 2015, 11, 707–719, doi:10.3762/bjoc.11.81

• resulted in acetylation of the glycan thus blocking the glycan’s hydroxy groups. The generality of this method was illustrated with the synthesis of 16 different DNA conjugates containing one or two glycan units. Analysis of glycan-modified duplexes by CD spectroscopy indicated minimal perturbation of the

Synthesis of a hexasaccharide partial sequence of hyaluronan for click chemistry and more

• Marina Bantzi,
• Stephan Rigol and
• Athanassios Giannis

Beilstein J. Org. Chem. 2015, 11, 604–607, doi:10.3762/bjoc.11.67

• reducing conditions (Zn, AcOH) [28] and subsequently the liberated amino groups were acetylated to furnish compound 8. Eventually, the silyl group and all benzylidene moieties were removed by treatment with Olah's reagent to give, after acetylation, derivative 9. Finally, oxidation of the terminal olefinic

Chemoselective O-acylation of hydroxyamino acids and amino alcohols under acidic reaction conditions: History, scope and applications

• Tor E. Kristensen

Beilstein J. Org. Chem. 2015, 11, 446–468, doi:10.3762/bjoc.11.51

• therefore be an important theme throughout most of this text. However, this methodology is founded upon a few pioneering but more narrow-scoped precursor techniques. Early chemoselective O-acetylation of hydroxyamino acids In 1942, Sakami and Toennies reported a method for the preparation of the O-acetyl

• derivatives of naturally occurring hydroxyamino acids (Scheme 1), a method that was also patented [9][10]. Being mindful of the known accelerating effect of the presence of acids in acetylation reactions of alcohols with acetic anhydride as well as the inhibitory effect of strong acids on the acetylation of

• amines with acetic anhydride, Sakami and Toennies scrutinized this effect through use of perchloric acid (HClO4), at first during titration experiments involving the acetylation of certain amino acids. They then exploited this reactivity pattern to develop a preparatory method for the class of O

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

• amino acids and the more reactive HATU/HOAt/NMM cocktail in NMP for attachment of building block 11 and a triethylene glycol spacer [52], the desired glycopeptide was assembled. Release from the resin using TFA/iPr3SiH/water (10:1:1) followed by careful de-O-acetylation with NaOMe/MeOH (pH 9.0) and

First chemoenzymatic stereodivergent synthesis of both enantiomers of promethazine and ethopropazine

• Paweł Borowiecki,
• Daniel Paprocki and
• Maciej Dranka

Beilstein J. Org. Chem. 2014, 10, 3038–3055, doi:10.3762/bjoc.10.322

• that generated ester (R)-(−)-6a was enantiomerically pure (>99% ee) regardless of the time and the conversion. In turn, the reaction rate was considerably improved in Novozym 435-catalyzed analytical scale acetylation. This revealed that Candida antarctica lipase B (CAL-B) immobilized on acrylic resin

• ≈ MTBE ≈ Et2O > toluene ≈ vinyl acetate, and the reaction enantioselectivity: toluene > vinyl acetate > n-hexane > MTBE ≈ Et2O > pentane. As it was observed, the acetylation reaction in toluene was mostly enantioselective (E = 180), thus transforming the racemic starting material (±)-3 into optically

• experiments, this extremely enantioselective lipase preparation afforded recovery of ester (R)-(−)-6a with perfect optical purity (>99% ee) at a conversion in the rage of 39–49% (Table 2, entries 4–7). On the other hand, since the Lipozyme TL IM-catalyzed acetylation tends to cease before achieving 50

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

• the removal of the benzyl group was accomplished by hydrogenation using Pearlman’s catalyst [36]. Finally the acetates were removed by Zemplén de-O-acetylation [37] using sodium methoxide to afford the target pentasaccharide 1 in 58% overall yield (Scheme 2). Conclusion In summary, a [3 + 2] block

Gold(I)-catalysed synthesis of a furan analogue of thiamine pyrophosphate

• Amjid Iqbal,
• El-Habib Sahraoui and
• Finian J. Leeper

Beilstein J. Org. Chem. 2014, 10, 2580–2585, doi:10.3762/bjoc.10.270

• strong inhibitor of ZmPDC with picomolar affinity. Friedel–Crafts acetylation of the furan at C-2 was successful which opens the possibility of synthesising furan analogues of the enzymic reaction intermediates. Structure of thiamine diphosphate (ThDP, 1). Time course inactivation of ZmPDC by various

A simple copper-catalyzed two-step one-pot synthesis of indolo[1,2-a]quinazoline

• Chunpu Li,
• Lei Zhang,
• Shuangjie Shu and
• Hong Liu

Beilstein J. Org. Chem. 2014, 10, 2441–2447, doi:10.3762/bjoc.10.254

• ]quinazoline derivatives. (3) This protocol is performed as a two-step reaction in one pot. Results and Discussion Substituted N-(2-iodophenyl)acetamides 1 were synthesized from substituted 2-iodoaniline by acetylation [31][32]. Substituted o-iodobenzaldehydes 3 were prepared from 2-iodobenzoic acid

Synthesis of novel conjugates of a saccharide, amino acids, nucleobase and the evaluation of their cell compatibility

• Dan Yuan,
• Xuewen Du,
• Junfeng Shi,
• Ning Zhou,
• Abdulgader Ahmed Baoum and
• Bing Xu

Beilstein J. Org. Chem. 2014, 10, 2406–2413, doi:10.3762/bjoc.10.250

• . Synthesis Schemes 1–4 show the syntheses of the SAN conjugates formed by the reaction of the amino acid segment with the nucleobase and the saccharide derivative. The key steps include N-alkylation, acetylation, solid-phase peptide synthesis (SPPS) and N-hydroxysuccinimide (NHS)/N,N-diisopropylcarbodiimide

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

• performed at an early stage of the synthetic route than on valuable advanced intermediates. Accordingly, the azide reduction with NiCl2/NaBH4 protocol [29] occurred smoothly on the previously described [25] silyl glycoside 4, and after standard N-acetylation furnished acetamide 5 in high yield (Scheme 1

Expanding the scope of cyclopropene reporters for the detection of metabolically engineered glycoproteins by Diels–Alder reactions

• Anne-Katrin Späte,
• Verena F. Schart,
• Julia Häfner,
• Andrea Niederwieser,
• Thomas U. Mayer and
• Valentin Wittmann

Beilstein J. Org. Chem. 2014, 10, 2235–2242, doi:10.3762/bjoc.10.232

• sugars 1 and 2 we neutralized the corresponding hexosamine hydrochlorides 5 and 6 with sodium methoxide and coupled them to the activated cyclopropene 7 (Scheme 2), the synthesis of which we reported previously [24]. Subsequent acetylation of the carbamates 8 and 9 gave Ac4GlcNCyoc (1) and Ac4GalNCyoc (2

• anhydride (10 mL) was added. After stirring for 24 h at room temperature additional 5 mL acetic anhydride were added to complete the acetylation. After additional 24 h the solvents were evaporated under reduced pressure. The residue was dissolved in CH2Cl2 (250 mL), washed with 10 % aq KHSO4 (200 mL), satd

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

• reaction furnished olefins 2a and 2b after acetylation in quantitative yield (Scheme 1). In the gluco-case a yield of 70% for 2c was obtained owing to incomplete consumption of the starting material 1c. Ozonolysis of the olefins 2 was performed using thiourea as reducing agent. Subsequently the generated 2

• followed by N-acetylation with N-acetoxyphthalimide did not afford products 8a–c in acceptable yields and/or purity. Since compounds 8a–c could not be purified by conventional silica gel chromatography we decided to perform an additional acetylation step in order to avoid reversed-phase HPLC and to

Synthesis and optical properties of pyrrolidinyl peptide nucleic acid carrying a clicked Nile red label

• Nattawut Yotapan,
• Chayan Charoenpakdee,
• Pawinee Wathanathavorn,
• Boonsong Ditmangklo,
• Hans-Achim Wagenknecht and
• Tirayut Vilaivan

Beilstein J. Org. Chem. 2014, 10, 2166–2174, doi:10.3762/bjoc.10.224

• completion of the synthesis, the N-terminal Fmoc group was removed and the free amino group was capped by acetylation. The acpcPNA on the solid support was spilt to 0.5 µmol portions for a further labeling experiment and treated with 1:1 dioxane/aqueous NH3 at 60 °C overnight to remove the nucleobase- and

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

Palladium-catalysed cyclisation of alkenols: Synthesis of oxaheterocycles as core intermediates of natural compounds

• Miroslav Palík,
• Jozef Kožíšek,
• Peter Koóš and
• Tibor Gracza

Beilstein J. Org. Chem. 2014, 10, 2077–2086, doi:10.3762/bjoc.10.216

• olefination using diethyl carbethoxyethylidenephopsphonate. Reduction of the resultant ester with DIBAL-H in dichloromethane afforded partially protected triol 36 in 39% yield over five steps. Finally, acetylation of the primary hydroxy group and subsequent removal of the acetonide provided the target

• compound 37 in good yield (77%). Synthesis of the similar substrate rac-42 having two conjugated double bonds is shown in Scheme 5. The synthesis started from the known acetate 38, which was obtained by acetylation of commercially available non-3-ene-1-ol [34]. Epoxidation of acetate 38 with MCPBA 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

• that the application of these reagents favours the addition of Grignard reagents to carbonyl compounds to afford higher yields [20][21][22]. Since all attempts to separate and purify carbinols 4–7 using column chromatography were unsuccessful even after acetylation, their physical and spectral data are

Supercritical carbon dioxide: a solvent like no other

• Jocelyn Peach and
• Julian Eastoe

Beilstein J. Org. Chem. 2014, 10, 1878–1895, doi:10.3762/bjoc.10.196

• ) (PMA - Table 2, compound 22) has a greater degree of acetylation than poly(vinyl acetate) (PVAc - Table 2, compound 23) but has a much higher melting point and is insoluble in CO2 [84]. A significant amount of experimental and theoretical work has been carried out on the addition of CO2-philic moieties

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

• showed that the acetylation of the furanose hydroxy groups resulted in a dramatic decrease in anti-leishmanian activity from 10.6 ± 1.3 µM (63a) to 139 µM (64b). Compound 65 was active against the cowpox virus in human foreskin fibroblast cells (EC50 = 2.0 ± 0.3 µM) [93] and showed anti-leishmanian

Orthogonal dual thiol–chloroacetyl and thiol–ene couplings for the sequential one-pot assembly of heteroglycoclusters

• Michele Fiore,
• Gour Chand Daskhan,
• Baptiste Thomas and
• Olivier Renaudet

Beilstein J. Org. Chem. 2014, 10, 1557–1563, doi:10.3762/bjoc.10.160

• α-D-ManSH 1 and β-D-GlcNAcSH 2 were prepared from the corresponding bromo peracetyl and chloro peracetyl sugars by treatment with potassium thioacetate followed by de-O-acetylation under standard conditions [24]. Cyclopeptide 3 displaying two orthogonal functionalities, i.e., four lysine residues

Synthesis and solvodynamic diameter measurements of closely related mannodendrimers for the study of multivalent carbohydrate–protein interactions

• Yoann M. Chabre,
• Alex Papadopoulos,
• Alexandre A. Arnold and
• René Roy

Beilstein J. Org. Chem. 2014, 10, 1524–1535, doi:10.3762/bjoc.10.157

• follow a conceptually identical strategy to the one described above for trimers 5 and 9. Toward this goal, propargylated 9-mer scaffold 10 [17] was treated under the same CuAAc conditions with azide 3 to provide peracetylated 11 in 83% yield which upon Zemplén de-O-acetylation gave 12 in essentially

• :0 to 90:10) afforded the desired glycocluster. Procedure B: Zemplén de-O-acetylation procedure for insoluble hydroxylated derivatives The acetylated compound was dissolved in anhydrous MeOH and a solution of sodium methoxide (1 M in MeOH, 5 µL every 20 min until precipitation) was added. An

Design, automated synthesis and immunological evaluation of NOD2-ligand–antigen conjugates

• Marian M. J. H. P. Willems,
• Gijs G. Zom,
• Nico Meeuwenoord,
• Ferry A. Ossendorp,
• Herman S. Overkleeft,
• Gijsbert A. van der Marel,
• Jeroen D. C. Codée and
• Dmitri V. Filippov

Beilstein J. Org. Chem. 2014, 10, 1445–1453, doi:10.3762/bjoc.10.148

• neopentyl glycol at 60 °C and careful monitoring of the reaction progress led to compound 17 in 88% yield. Acetylation of 17 then afforded compound 18. Stabilization of the glycosidic linkage by the installment of electron-withdrawing groups proved to be successful, and the treatment of 18 with 20% TFA in

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

• and chitosan derivatives for pharmaceutical applications was described [22]. Chitosan is the polysaccharide obtained from the abundant chitin by alkali or enzymatic degradation. It consists of a backbone of β-(1→4)-linked D-glucosamine units with a variable degree of N-acetylation. The protonated

A complete series of 6-deoxy-monosubstituted tetraalkylammonium derivatives of α-, β-, and γ-cyclodextrin with 1, 2, and 3 permanent positive charges

• Martin Popr,
• Simona Hybelbauerová and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2014, 10, 1390–1396, doi:10.3762/bjoc.10.142

• ], acetylation [11] or hydroxypropylation [12] and perfacial substitution of all primary 6-OH hydroxy groups by iodine [13]. The products of these reactions are easily accessible in high amounts and are used in the pharmaceutical industry [14] or as precursors for further derivatizations. Monosubstituted CDs