Orthogonal protection of saccharide polyols through solvent-free one-pot sequences based on regioselective silylations

• Serena Traboni,
• Emiliano Bedini and
• Alfonso Iadonisi

Beilstein J. Org. Chem. 2016, 12, 2748–2756, doi:10.3762/bjoc.12.271

• Serena Traboni Emiliano Bedini Alfonso Iadonisi Department of Chemical Sciences, University of Naples Federico II, Via Cinthia 4, 80126, Naples, Italy 10.3762/bjoc.12.271 Abstract tert-Butyldimethylsilyl (TBDMS) and tert-butyldiphenylsilyl (TBDPS) are alcohol protecting groups widely employed in

• experimentally simple tool for the straightforward access to saccharide building-blocks useful in organic synthesis. Keywords: carbohydrates; one-pot synthesis; regioselective protection; silyl protecting group; solvent-free reaction; Introduction The application of an orthogonal set of protecting groups

• to a broad range of conditions and feasible removal under conditions compatible with many other used alcohol protecting groups [1][2][3]. For this reason, silyl protecting groups are often serving as temporary protecting groups with polyol and saccharide substrates. The most robust and adopted silyl

β-Amino functionalization of cinnamic Weinreb amides in ionic liquid

• Yi-Ning Wang,
• Guo-Xiang Sun and
• Gang Qi

Beilstein J. Org. Chem. 2016, 12, 2372–2377, doi:10.3762/bjoc.12.231

• reaction conditions required for the removal of the N-protecting groups. With the aminochlorination developed in the past few years [31], we found that when the aminochlorination reactions of α,β-unsaturated ketones 3 were carried out in ionic liquid, [BMIM][NTf2] (1-n-butyl-3-methylimidazolium bis

• -protecting groups is relatively easier than those shown above; and 3) the ionic liquids are environmentally friendly and can be readily recycled. Results and Discussion The first attempt was to conduct the aminochlorination reaction of N-methoxy-N-methylcinnamoylamide (5a) in acetonitrile by using 2-NsNCl2

• achieved by the aminochlorination of α,β-unsaturated Weinreb amides. The new process has the advantages that the starting materials can be easily achieved and the N-protecting groups simply removed. Additionally, the reactions can be readily performed in the ionic liquid [BMIM][NTf2] at room temperature

Useful access to enantiomerically pure protected inositols from carbohydrates: the aldohexos-5-uloses route

• Felicia D’Andrea,
• Giorgio Catelani,
• Lorenzo Guazzelli and
• Venerando Pistarà

Beilstein J. Org. Chem. 2016, 12, 2343–2350, doi:10.3762/bjoc.12.227

• precursors are employed as starting materials. As an example of application of the method, the indirect selective protection of secondary inositols’ hydroxy functions, by placing specific protecting groups on the aldohexos-5-ulose precursor has been presented. Keywords: aldohexos-5-uloses; inositols

• group (position 6). This 2,3,6-cis arrangement of the aldol products was observed irrespective to the stereochemistry of the other two positions (4 and 5), corresponding to the C-2 and C-3 of the parent dicarbonyl derivative. To determine the effect of additional protecting groups on the reaction, the

• stereoselectivity in accordance with the predicted stereo-outcome. In this way, the orthogonal protecting groups (allyl and naphthalenylmethyl) installed on aldohexos-5-ulose 20, differentiated the two 1,2-cis hydroxy couples (2,3 and 4,5 positions) of 22 which can be easily transformed further in a selective

Enduracididine, a rare amino acid component of peptide antibiotics: Natural products and synthesis

• Darcy J. Atkinson,
• Briar J. Naysmith,
• Daniel P. Furkert and
• Margaret A. Brimble

Beilstein J. Org. Chem. 2016, 12, 2325–2342, doi:10.3762/bjoc.12.226

• -hydroxyenduracididine 52 using the same procedure. The new route proved more efficient than the previous report and provided access to both diastereomers suitably armed with orthogonal protecting groups. Synthesis of (±)-enduracididine and (±)-allo-enduracididine by Du Bois et al.: The synthesis of (±)-enduracididine

• protected linear precursor 115. Cleavage of the TBS and methyl ester protecting groups afforded seco-acid 116. However, during the hydrolysis step, two of the three Cbz groups were cleaved from the enduracididine residue, and the position of the remaining Cbz and CO2H could not be determined. It was decided

• that final deprotection of the remaining enduracididine protecting groups would take place after formation of the macrocycle. Treatment of linear precursor 116 with modified Shiina macrolactonisation conditions reported by Batey et al. [74] of 2-methyl-6-nitrobenzoic anhydride (MNBA), DMAP and Dy(OTf)3

The direct oxidative diene cyclization and related reactions in natural product synthesis

• Juliane Adrian,
• Leona J. Gross and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2016, 12, 2104–2123, doi:10.3762/bjoc.12.200

• protecting groups. The first total synthesis of membrarollin (62, Scheme 13) was finally disclosed by Brown and co-workers in 2009 [107]. Similarly starting from 1-dodecyne (56), triene system 61 was selectively oxidized using a permanganate-mediated oxidative cyclization affording two separable

Synthesis of the C8’-epimeric thymine pyranosyl amino acid core of amipurimycin

• Pramod R. Markad,
• Navanath Kumbhar and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2016, 12, 1765–1771, doi:10.3762/bjoc.12.165

• including solvent, Lewis acid, and protecting groups on the nucleobase or sugar; we thought of synthesizing the peracylated anhydrosugar to alter its reactivity towards glycosylation [22]. In this regard, anhydrosugar 15 was subjected to 10% Pd/C and Et3SiH (for deprotection of the benzyl functionality and

Beta-hydroxyphosphonate ribonucleoside analogues derived from 4-substituted-1,2,3-triazoles as IMP/GMP mimics: synthesis and biological evaluation

• Tai Nguyen Van,
• Audrey Hospital,
• Corinne Lionne,
• Lars P. Jordheim,
• Charles Dumontet,
• Christian Périgaud,
• Laurent Chaloin and
• Suzanne Peyrottes

Beilstein J. Org. Chem. 2016, 12, 1476–1486, doi:10.3762/bjoc.12.144

• -protected nucleotides 3a–o (Scheme 2) in moderate to good yields. Removal of the sugar protecting groups (acetyl and benzoyl) in basic conditions resulted in the formation of the nucleotides 4a–q (Scheme 2), which were then treated by trimethylsilyl bromide (TMSBr) to generate the corresponding phosphonic

• water and extracted with EtOAc, the organic layers were combined and dried over with MgSO4 and concentrated under reduced pressure. The crude material was purified by flash chromatography (CH2Cl2/EtOAc) to give the desired product. General procedure D for removal of sugar protecting groups: The

Automated glycan assembly of a S. pneumoniae serotype 3 CPS antigen

• Markus W. Weishaupt,
• Stefan Matthies,
• Mattan Hurevich,
• Claney L. Pereira,
• Heung Sik Hahm and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2016, 12, 1440–1446, doi:10.3762/bjoc.12.139

• step with the activator prior to each glycosylation cycle greatly increased the yields by neutralizing any residual base from deprotection steps in the synthetic cycle. This process improvement is applicable to AGA of many other oligosaccharides. Keywords: automation; glycosylation; protecting groups

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• led to low conversion. The use of potassium tert-butoxide was found to be essential to achieve good reactivity and enantioselectivity. Other amino-protecting groups (Boc, phthalimido) or tertiary N-methylated variants rendered the 1,4-acceptor unreactive. Glorius and co-workers proposed that an

NeoPHOX – a structurally tunable ligand system for asymmetric catalysis

• Jaroslav Padevět,
• Marcus G. Schrems,
• Robin Scheil and
• Andreas Pfaltz

Beilstein J. Org. Chem. 2016, 12, 1185–1195, doi:10.3762/bjoc.12.114

• determined by X-ray diffraction and compared with known phosphinooxazoline complexes. We were interested to see whether the differences in steric shielding of the coordination sphere by the protecting groups on the tertiary alcohol function correlated with the hydrogenation results. From the obtained crystal

Chiral cyclopentadienylruthenium sulfoxide catalysts for asymmetric redox bicycloisomerization

• Barry M. Trost,
• Michael C. Ryan and
• Meera Rao

Beilstein J. Org. Chem. 2016, 12, 1136–1152, doi:10.3762/bjoc.12.110

• reaction for the synthesis of Tris-protected [3.1.0] pyrrolidines, it occurred to us that protecting groups other than Tris may be equally effective for the [3.1.0] system. The Tris group was chosen during our optimization of the six-membered ring system (Table 5), which may have significantly different

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• (Scheme 1) [14]. 3-Allyl-3-hydroxyoxindoles were obtained in 89–98% yield and with 32–86% ee when the reactions were carried out at −60 °C using 5 mol % of CNN pincer Pd complex (cat. 1). Substituents attached to the isatin aromatic ring and N-protecting groups were important in controlling the

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

• is remarkable that this protocol avoids using O-protecting groups or the Garner aldehyde which have been used extensively in the synthesis of related compounds. Conclusion In summary, this simple protocol described herein enables a rapid access to a number of useful enantiopure allylic amines from

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

• guanidinylation reagent 55. With the protected epicapreomycidine precursor 56 in hand, the Boc and acetonide protecting groups were removed. Urea formation with the valine derivative 57 with final oxidation of the primary hydroxy function afforded the desired dipeptide 58 [78] (Scheme 7). Furthermore, Ducho et al

• (5'S)-configuration, contrary to the results of MIC value determination. Further studies were then carried out with (5'R)-derivatives only, i.e., with 5'-epimers of the parent natural products. The influence of protecting groups was examined applying a strategy of stepwise deprotection. This led to

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

• -anhydrohexopyranoses were then converted into the target fluoro analogs of D-glucosamine and D-galactosamine (Scheme 1). Dual protection of the anomeric and primary hydroxy groups in the form of the 1,6-anhydro bridge reduced the number of protecting groups, and the rigid bicyclic skeleton of 1,6-anhydrohexopyranoses

Iridium/N-heterocyclic carbene-catalyzed C–H borylation of arenes by diisopropylaminoborane

• Mamoru Tobisu,
• Takuya Igarashi and
• Naoto Chatani

Beilstein J. Org. Chem. 2016, 12, 654–661, doi:10.3762/bjoc.12.65

• derivatives by treatment with protecting groups in a one-pot reaction sequence. The reactivity of 1g has previously been well-exploited in catalytic borylation of aryl halides [22][23][24][25][26][27]. Herein, we report the C–H borylation of arenes using 1g catalyzed by an Ir/N-heterocyclic carbene (NHC

• ) complex bearing an ICy ligand was the most efficient catalyst. The initially formed aminoborylated products can readily be converted to the corresponding organoboron compounds bearing various boron-protecting groups. Experimental Procedure for the Ir-catalyzed borylation of heteroarenes using 1g In a

Studies on the synthesis of peptides containing dehydrovaline and dehydroisoleucine based on copper-mediated enamide formation

• Franziska Gille and
• Andreas Kirschning

Beilstein J. Org. Chem. 2016, 12, 564–570, doi:10.3762/bjoc.12.55

• total synthesis when the guanidine group has either to be liberated by the removal of the protecting groups or used for the introduction to the corresponding ornithine residue. These results demonstrate that the copper-mediated cross-coupling reaction depends on the functional groups present in the

• peptide containing the vinyl iodide moiety and on the chosen protecting groups. Vinyl iodides bearing an arginine moiety gave a significantly reduced yield of the desired cross-coupling product compared to the corresponding ornithine derivatives. Furthermore, it turned out that the Alloc and Pbf

• protecting groups are not compatible for this enamide forming protocol. The best results were obtained by using the Boc-protected amide 30 and ornithine-containing vinyl iodides 24 and 28 (Scheme 5). It needs to be noted that the presence of a Cbz protecting group in dehydrooligopeptides is problematic

A selective and mild glycosylation method of natural phenolic alcohols

• Mária Mastihubová and
• Monika Poláková

Beilstein J. Org. Chem. 2016, 12, 524–530, doi:10.3762/bjoc.12.51

• Acetyl-protecting groups are the simplest choice also for the protection of the glycone part since the deprotection of both, sugar and aromatic moieties, can be accomplished in one step. Naturally occurring O-glycosides possess mostly 1,2-trans-glycosidic linkages. Therefore, neighbouring group

Diastereoselective synthesis of new O-alkylated and C-branched inositols and their corresponding fluoro analogues

• Charlotte Collet,
• Françoise Chrétien,
• Yves Chapleur and
• Sandrine Lamandé-Langle

Beilstein J. Org. Chem. 2016, 12, 353–361, doi:10.3762/bjoc.12.39

• case of the O-alkylated inositols a three carbon arm was envisioned whereas for the C-branched derivatives two and three carbon atom arms were used. For the fluorinated inositols, we developed a synthetic route with easily removing protecting groups, as acetates, suitable for PET imaging application

• the access to myo-10 and scyllo-10 in 78% and 75% yield, respectively. The O-alkylated inositol derivatives myo-1 and scyllo-1 were obtained quantitatively by removing of the benzyl protecting groups of compounds myo-10 and scyllo-10 by hydrogenation under pressure [45] using palladium hydroxide as

• and 92% yield, respectively [48]. All protecting groups of myo-13 and scyllo-13 were removed by the treatment with Na0 in MeOH [49], which gave quantitatively the fully deprotected fluorinated O-alkylated inositols myo-2 and scyllo-2. Synthesis of C-branched myo- and scyllo-inositol derivatives

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

• the use of Boc-protecting groups. Reduction of 6-iodoindole with NaBH3CN in HOAc afforded 6-iodoindoline (38, 90%) [47], which was subsequently TIPS-protected (39, Scheme 6). Hydroxyalkylation of 39 with β-cyclocitral (30) gave cyclization precursor 40 (68%). We were pleased to find that this time the

Application of 7-azaisatins in enantioselective Morita–Baylis–Hillman reaction

• Qing He,
• Gu Zhan,
• Wei Du and
• Ying-Chun Chen

Beilstein J. Org. Chem. 2016, 12, 309–313, doi:10.3762/bjoc.12.33

• enantioselectivity was observed for products 3h and 3i (Table 2, entries 8 and 9). 7-Azaisatins with different N-protecting groups were also applied to the MBH reaction with N-phenylmaleimide (2a), including methoxymethyl (MOM), benzyl (Bn) and 4-chlorophenyl substituents. All of them showed a lower reactivity and

Amino-functionalized (meth)acryl polymers by use of a solvent-polarity sensitive protecting group (Br-t-BOC)

• Helmut Ritter,
• Monir Tabatabai and
• Markus Herrmann

Beilstein J. Org. Chem. 2016, 12, 245–252, doi:10.3762/bjoc.12.26

• )acrylates [2]. Therefore, for the synthesis of amino-containing (meth)acrylic monomers and polymers suitable amino-protecting groups are required. Classical protecting groups such as ammonium salts, F-MOC, Z- or t-BOC, respectively are readily available. Regarding to this aspect, we published some papers

• about polymer protecting groups about three decades ago [3][4][5][6][7]. However, they are limited in application by certain restrictions on the deprotection conditions. Therefore, there is a continued interest in developing new protecting groups which can be cleaved by different mechanisms. Keeping

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

• , particularly for iminium ions, progress is on-going to determine stable precursors to the requisite iminium ion intermediates and to identify readily removed protecting groups. Given the potential of enantioselective, copper-catalyzed alkynylations to deliver important scaffolds, significant effort is still

Synthesis of cyclic N¹-pentylinosine phosphate, a new structurally reduced cADPR analogue with calcium-mobilizing activity on PC12 cells

• Ahmed Mahal,
• Stefano D’Errico,
• Nicola Borbone,
• Brunella Pinto,
• Agnese Secondo,
• Valeria Costantino,
• Valentina Tedeschi,
• Giorgia Oliviero,
• Vincenzo Piccialli and
• Gennaro Piccialli

Beilstein J. Org. Chem. 2015, 11, 2689–2695, doi:10.3762/bjoc.11.289

• allowed the removal of both the OCE phosphate protecting groups together with the acetate function, thus obtaining the key intermediate 18 as triethylammonium salt after HPLC purification. The derivate 18, dissolved in DMF at the final concentration of 2 mM was treated with EDC (1.2 equiv) and the

Selectively fluorinated cyclohexane building blocks: Derivatives of carbonylated all-cis-3-phenyl-1,2,4,5-tetrafluorocyclohexane

• Mohammed Salah Ayoup,
• David B. Cordes,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2015, 11, 2671–2676, doi:10.3762/bjoc.11.287

• demonstrated that 4 can be elaborated in a relatively straightforward manner by mainstream reactions of electrophilic aromatic substitution [7]. This extended to the synthesis of cyclohexane substituted (S)-L-phenylalanines with orthogonal protecting groups suitable for their incorporation into peptides [8