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

• 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

• after in situ peracetylation (Table 2, entry 8). The scope of the TBAB-catalyzed silyl protection under solvent-free conditions was next examined for the regioselective attachment of TBDPS (Table 2, entries 9–13), a commonly used silyl protecting group bulkier than TBDMS and more resistant to acidic

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

• Dodd et al. published a synthesis of protected enduracididine using an azide ring opening of a chiral aziridine as the key step (Scheme 3) [55]. The 9-phenylfluorenyl (PhF) protecting group was employed to help prevent undesired copper coordination during the key aziridation step. The synthesis relied

• protecting group manipulation and installation of the guanidine using S-methylisothiourea 33 (Scheme 5). Mitsunobu cyclisation followed by deprotection and oxidation afforded the azido acids 38 and 39 in 40% yield over 8 steps from amino azides 36 and 37. Synthesis of β-hydroxyenduracididine by Nieuwenhze et

• al.: In 2010, Nieuwenhze and Oliver reported a synthesis of protected β-hydroxyenduracididines 40 and 41 making use of intermediate nosylamine 42 (Scheme 6) [57]. The synthesis of 42 began with alkene 43, available from (S)-Garner’s aldehyde. Cleavage of the protecting group allowed installation of

Tunable microwave-assisted method for the solvent-free and catalyst-free peracetylation of natural products

• Manuela Oliverio,
• Paola Costanzo,
• Monica Nardi,
• Carla Calandruccio,
• Raffaele Salerno and
• Antonio Procopio

Beilstein J. Org. Chem. 2016, 12, 2222–2233, doi:10.3762/bjoc.12.214

• balanced by the absence of catalyst and by the reaction speed due to microwaves. The applied P-program was compatible with the N-Boc protecting group already present on the tyrosine methyl ester 8. Concerning salbutamol (9) the reported yield was referred to the peracetylated product 9a even if a

Regiocontroled Pd-catalysed C5-arylation of 3-substituted thiophene derivatives using a bromo-substituent as blocking group

• Mariem Brahim,
• Hamed Ben Ammar,
• Jean-François Soulé and
• Henri Doucet

Beilstein J. Org. Chem. 2016, 12, 2197–2203, doi:10.3762/bjoc.12.210

• -phenylthiophene (27) in 60% yield. A higher yield of 80% in 28 was obtained for the coupling of 16 with phenylboronic acid. In order to further demonstrate that a bromo-substituent at C2-position of the thiophenes can be considered as a protecting group, we removed it via palladium-catalysed hydrogenolysis

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

• compound 9 containing two hydroxy groups and the cyanoethyl protected thiol group was converted into the phosphoramidite being compatible with conditions of solid-phase oligonucleotide synthesis. The DMTr protecting group was incorporated and the conversion of the secondary alcohol 10 to phosphoramidite 11

• 55 °C. The Fmoc protecting group of oligonucleotide ON1 was removed, however, the cyanoethyl group as a base-labile protecting group of the thiol was not removed quantitatively from the oligonucleotide ON2 [54][55][56][57][58]. Dynamic template-driven assembly of double strand libraries

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

• obtained, which was subsequently cyclized. The reaction yielded the desired THF diol 10a in 61% as a single diastereoisomer together with over-oxidized 10b as side product. The total synthesis was finally achieved from 10a via some protecting group operations and an oxidation of the primary alcohol to the

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

• 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

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

• diketone 257, which cyclized to hemiketal 258 as the products (Scheme 79) [354]. As the above reaction did not allow the isolation of hydroperoxide 254, an alternative strategy towards this compound was developed. The introduction of a protecting group into endoperoxide 253 using 2-methoxypropene gave

Total synthesis of leopolic acid A, a natural 2,3-pyrrolidinedione with antimicrobial activity

• Atul A. Dhavan,
• Rahul D. Kaduskar,
• Loana Musso,
• Leonardo Scaglioni,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2016, 12, 1624–1628, doi:10.3762/bjoc.12.159

• A straightforward route to the intriguing 2,3-pyrrolidinedione system appeared to be the Michael addition of a suitable amine to ethyl acrylate, followed by a Dieckmann cyclization with diethyl oxalate [10][11]. We chose the p-methoxybenzyl (PMB) protecting group for the amine, because of its facile

• DIBAL-H gave the corresponding primary alcohol, which was converted into bromide 5 by Appel reaction with PPh3 and CBr4. The phosphonium salt obtained from this bromide was subjected to a Wittig reaction with nonanal, to afford compound 6 [12]. Attempts to remove the PMB protecting group (CAN, DDQ, TFA

• it could also act as a NH-protecting group in the following steps. However, as the ureido fragment would interfere with the reduction of the ester group on the nucleus, we opted for installing sequentially the valine, then the phenylalanine residue. Thus, compound 7 was coupled with pentafluorophenyl

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

• block 1 was designed (Figure 2). A levulinoyl (Lev) ester was chosen as temporary protecting group (TPG) since the Fmoc (fluorenylmethoxycarbonyl) group led to a loss of stereocontrol during glycosylations with this glucuronic acid (GlcA) building block (data not shown). Glucose building blocks 2 and 3

• ]. The building blocks were synthesized in high yields using standard protecting group chemistry (see Supporting Information File 1). Solid support 4 was prepared according to an established procedure [28]. The automated glycosylation protocol employed three times three equivalents of building block to

• maintained for 30 min. The temporary Fmoc protecting group was cleaved with triethylamine in DMF (N,N-dimethylformamide; 10% v/v). The Lev protecting group was removed using hydrazine monohydrate in pyridine/acetic acid (3:2 v/v). The crude oligosaccharide products were cleaved from the solid support by

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

• protecting group, the steric properties of the ligand can be optimized for a specific application. PHOX ligands of this type have been previously prepared from serine and successfully used in iridium-catalyzed hydrogenation [29][30]. Synthesis of serine- and threonine-derived NeoPHOX ligands The synthesis

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

• amide to the Lewis acidic ruthenium center (Table 5, entry 7). Gratifyingly, utilizing the bulkier 2,4,6-triisopropylbenzenesulfonyl group (Tris) significantly improved the er of protected piperidine 35 to 15.0:85.0. Because of its differential impact on selectivity, this protecting group was pursued

• isomerization known to date. We were able to demonstrate that the nitrogen protecting group on the 1,7-enynes had a significant impact on the enantioselectivity of the redox bicycloisomerization as did the choice of solvent. Extending the chemistry to the 1,6-enynes, we showed that these substrates were much

• ligands. Solvent effects on asymmetric redox bicycloisomerization reaction as described in [43]. Effect of the catalyst structure on the redox bicycloisomerization as described in [43]. Comparison of complex 1 to other catalyst systems as described in [43]. Effect of the nitrogen protecting group on

Synthesis of a deuterated probe for the confocal Raman microscopy imaging of squalenoyl nanomedicines

• Eric Buchy,
• Branko Vukosavljevic,
• Maike Windbergs,
• Dunja Sobot,
• Camille Dejean,
• Simona Mura,
• Patrick Couvreur and
• Didier Desmaële

Beilstein J. Org. Chem. 2016, 12, 1127–1135, doi:10.3762/bjoc.12.109

• thioketal [38]. These results clearly showed that another protecting group must be used, avoiding the use of an acidic catalyst that triggered the cyclization cascade of the polyisoprenyl chain (Scheme 3). Despite this setback, the synthetic route seemed suitable to produce the desired material. Thus, the

• directly the alcohol 28 in 41% yield through concomitant reduction of the intermediate allylic chloride and cleavage of the silyl protecting group. The reductive cleavage of tert-butyldiphenylsilyl ethers by LiAlH4 has been previously noticed [39]. Jones oxidation straightforwardly completed the synthesis

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

• ). The generality of this protocol was examined using various isatin derivatives and all reactions proceeded smoothly within 15 min to give the desired products in good results regardless of the electronic properties of the substituents. Additionally, the N-protecting group of isatins was found to have a

• adducts were obtained in high yields (up to 92%) and with moderate to good enantioselectivities (up to 88% ee, Scheme 40) [57]. The substrate scope was examined, showing that the protecting group attached to the isatin amide was crucial for the enantioselectivity, while the electronic properties of

• substituents on the isatin aromatic ring had little effect on the reaction. Particularly, when the N-protecting group was methyl and triphenylmethyl (trityl), the corresponding products were obtained with extremely low enantioselectivities (25% and 4% ee, respectively). Pan and co-workers reported the first

A cross-metathesis approach to novel pantothenamide derivatives

• Jinming Guan,
• Matthew Hachey,
• Lekha Puri,
• Vanessa Howieson,
• Kevin J. Saliba and
• Karine Auclair

Beilstein J. Org. Chem. 2016, 12, 963–968, doi:10.3762/bjoc.12.95

• -methoxybenzaldehyde acetal protecting group in 9 is believed to tie back the alcohols and prevent them from coordinating and deactivating the ruthenium catalyst. When testing the scope of the metathesis reaction with 9, a variety of partners were chosen, including not only acrylic acid (10a), but also 2-vinylpyridine

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

• and threonine derivatives. Keywords: amino acids; olefination; protecting group free; synthetic methods; Wittig reactions; Introduction Allylic amines have received significant attention because they represent a common scaffold in diverse biologically relevant compounds and natural products [1]. In

• -protected α-amino esters requires three chemical steps, i.e. reduction, oxidation and olefination (Figure 1) [9][10]. When the benzyl group is used as protecting group for the nitrogen functionality, the method represents a variation of the well-known Reetz protocol [11]. In the particular case of serine

• ]. However, that preliminary study was limited to the use of phosphonium ylide reagents and commonly t-Boc (iBoc and Ac were used once) as N-protecting group. To the best of our knowledge, no further studies on the reaction conditions have been carried out. Instead, the method was applied to N-Ac aspartic

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 the benzoyl group and a subsequent reaction of the salt 24 with methanol upon quenching. A similar participation of a vicinal O-acetyl protecting group on reaction with DAST leading to the formation of an orthoacetate was reported [47]. Reaction of fluorohydrin 20 with DAST proceeded with

Gold-catalyzed direct alkynylation of tryptophan in peptides using TIPS-EBX

• Gergely L. Tolnai,
• Jonathan P. Brand and
• Jerome Waser

Beilstein J. Org. Chem. 2016, 12, 745–749, doi:10.3762/bjoc.12.74

• . Results and Discussion We started our investigation by attempting the alkynylation of valine-tryptophan dipeptide 4a as model substrate (Table 1). An often used carboxybenzyl (Cbz, Z) protecting group was chosen. Examining this substrate will tell if C2-alkynylation is possible in the presence of an ester

• , a carbamate and an amide protecting group. A promising result was obtained with 5 mol % gold chloride as catalyst at room temperature in acetonitrile (Table 1, entry 1). Although the reaction did not go to completion even after two days, the desired C2 alkynylation product 5a was obtained in 44

Asymmetric α-amination of 3-substituted oxindoles using chiral bifunctional phosphine catalysts

• Qiao-Wen Jin,
• Zhuo Chai,
• You-Ming Huang,
• Gang Zou and
• Gang Zhao

Beilstein J. Org. Chem. 2016, 12, 725–731, doi:10.3762/bjoc.12.72

• transformation (Table 1, entry 4). Different from N-Boc-oxindole, using N-unprotected oxindole and N-benzyl-substituted oxindole as the substrates, accomplished the reaction with every low enantioselectivity (Table 1, entries 7 and 8), incidated the N-Boc protecting group is crucial for this system. Next, the

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

• protecting group and the reaction conditions. It was found that ornithine – a suitable precursor – is better suited than arginine for achieving good yields for the C–N cross-coupling reaction. The optimized conditions were utilized for the synthesis of peptides 32, 33, 39 and 40 containing a neighboring

• in commonly good yields (Scheme 4). The coupling partners 18–23 (synthesis see Supporting Information File 1) all contain arginine or the precursor amino acid ornithine and they differ in the choice of the protecting group. These variations are important for gaining flexibility towards the end of the

• 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

• -benzyloxyphenyl)alkyl alcohol catalysed by Ag salts [9][18]. The final removal of the benzyl protecting group from the phenolic function of the aglycone by catalytic reduction can be however problematic in the case of more complex molecules containing for example double bonds (e.g., arenarioside) [30

Copper-mediated arylation with arylboronic acids: Facile and modular synthesis of triarylmethanes

• H. Surya Prakash Rao and
• A. Veera Bhadra Rao

Beilstein J. Org. Chem. 2016, 12, 496–504, doi:10.3762/bjoc.12.49

• preparation of the starting diarylmethanol 20, which was accomplished by the addition the anion from 9-bromophenanthrene [63] 19 to 4-methoxybenzaldehdye. The resulting diarylmethanol 20 was treated with bis(pinacolato)diboron [64] 10n, which has an 2-nitrobenzyl protecting group on the phenolic hydroxy group

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

• and coworkers for benzyl ether cleavage in the presence of Boc-protected amines when studying the late stages of the total synthesis of the trisindole alkaloid yatakemycin [44]. As an alternative, the 3,4-dimethoxybenzyl (DMB) protecting group was installed (13). We favored the DMB over the related

• 100 °C. Unfortunately, all reactions gave intractably complex mixtures. 1H and 19F NMR analysis suggested that cleavage of at least one Boc-protecting group had occurred. Additionally, the triflate was still visible in the 19F NMR spectrum, thus indicating that oxidative addition to the Pd catalyst

• ]indole 35 (21%). For the corresponding N-TIPS-protected indole 33, obtained from 29, yields of tetracyclic products 36 (7%) and 37 (2%) were very low and we observed the loss of the TIPS protecting group. Noteworthy, we did not detect regioisomeric indeno[2,1-g]indole products when starting from 33

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

• this in mind, the bromo-tert-butyloxycarbonyl (Br-t-BOC) group represents the first known solvent-polarity sensitive amino-protecting group. As shown in Figure 1, this group is stable in nonpolar solvents because of high activation energy and easily decomposes in a more polar environment because of

• reduced activation energy. This effect is a result of an increased polarity of the transition state in comparison to the starting molecule (Figure 1). In contrast to the classical t-BOC protecting group, the Br-t-BOC group can be easily removed without pH adjustments. Since the published papers from L. A

• . Carpino [8][9][10] and a first practical application in peptide synthesis [11] this protecting group was quasi forgotten. In the present work we report new Br-t-Boc-protected (meth)acrylic monomers and their polymerization through free radical polymerization. The kinetics of Br-t-BOC solvolysis of the

Hydroquinone–pyrrole dyads with varied linkers

• Hao Huang,
• Christoffer Karlsson,
• Maria Strømme,
• Martin Sjödin and
• Adolf Gogoll

Beilstein J. Org. Chem. 2016, 12, 89–96, doi:10.3762/bjoc.12.10

• , see Supporting Information File 2). According to a study by Liu et al. [19], the protecting group for 3-iodo pyrrole is essential in the Heck reaction involving pyrrole. Based on this suggestion, 3-iodo-1-tosyl-1H-pyrrole was also tested but did not result in any product. It is worth to mention that