Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates

• Yuichi Yoshimura,
• Hideaki Wakamatsu,
• Yoshihiro Natori,
• Yukako Saito and
• Noriaki Minakawa

Beilstein J. Org. Chem. 2018, 14, 1595–1618, doi:10.3762/bjoc.14.137

• reaction of trans-cyclobutane sulfoxide 59. The authors concluded that the stereochemistry of the sulfoxide and the nature of the protecting groups had no significant effect on the yield of the Pummerer-type glycosylation [47] (Scheme 8). Pummerer-type glycosylation, which was developed by our group

Synthesis of chiral 3-substituted 3-amino-2-oxindoles through enantioselective catalytic nucleophilic additions to isatin imines

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 1349–1369, doi:10.3762/bjoc.14.114

• yields (51–91%) and uniformly high enantioselectivities (92–99% ee), as shown in Scheme 1. Common protecting groups (R1), such as methyl, ethyl, 4-methoxybenzyl, methoxymethyl, phenyl and benzyl, were tolerated as well as various substituents (R2) on the aromatic ring of the isatins, including electron

• )substituted isatin imines (R1 = Me, Bn, H). Moreover, a range of electron-withdrawing and electron-donating groups on the aryl moiety (R2) as well as different N-carbamoyl protecting groups (R3 = t-Bu, Et, Bn) were compatible, providing generally high enantioselectivities (85 to >99% ee), except for the 5

The first Pd-catalyzed Buchwald–Hartwig aminations at C-2 or C-4 in the estrone series

• Ildikó Bacsa,
• Dávid Szemerédi,
• János Wölfling,
• Gyula Schneider,
• Lilla Fekete and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 998–1003, doi:10.3762/bjoc.14.85

• derivative [17][18]. The C(sp2)–N cross-coupling of the triflate was achieved with benzophenone imine or benzylamine. The removal of the protecting groups resulted in 3-aminoestrone in high yields. Schön et al. developed two convenient protocols for the preparation of 3-aminoestrone using Pd(OAc)2 and Pd2

Development of novel cyclic NGR peptide–daunomycin conjugates with dual targeting property

• Andrea Angelo Pierluigi Tripodi,
• Szilárd Tóth,
• Kata Nóra Enyedi,
• Gitta Schlosser,
• Gergely Szakács and
• Gábor Mező

Beilstein J. Org. Chem. 2018, 14, 911–918, doi:10.3762/bjoc.14.78

• the use of orthogonal protecting groups (Figure 1A). Previous studies indicated that the free ε-amino group of Lys does not have an impact on the biological activity [15][17]. To prove our assumption, a set of novel cyclic NGR peptide–Dau conjugates were developed in which the Lys was replaced by

• was observed in the case of conjugates 2, 3 and 4 obtained with a lower yield. The improvement was observed especially in the cyclization step that might be explained by the lack of bulky protecting groups on amino acids used instead of Lys. Chemostability of cyclic NGR peptide–daunomycin conjugates

A stereoselective and flexible synthesis to access both enantiomers of N-acetylgalactosamine and peracetylated N-acetylidosamine

• Bettina Riedl and
• Walther Schmid

Beilstein J. Org. Chem. 2018, 14, 856–860, doi:10.3762/bjoc.14.71

• improvement can be explained by a protonation of TMSN3 causing the in situ generation of highly reactive HN3 (Scheme 3). Additionally, no acidic work-up, as described by Miyashita et al., was necessary to gain the free alcohol on C5, which corroborates the proposed mechanism. The protecting groups were

Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

• Kartik Temburnikar and
• Katherine L. Seley-Radtke

Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65

• proved to be the most promising compound. The fluorine on 29 was replaced with a methoxy group after re-installing the isopropylidene protecting group. The cyano group was then converted to an amide and the methoxy converted to a hydroxy group. Removal of the protecting groups on the sugar gave 25, which

Synthesis and in vitro biochemical evaluation of oxime bond-linked daunorubicin–GnRH-III conjugates developed for targeted drug delivery

• Sabine Schuster,
• Beáta Biri-Kovács,
• Bálint Szeder,
• Viktor Farkas,
• László Buday,
• Zsuzsanna Szabó,
• Gábor Halmos and
• Gábor Mező

Beilstein J. Org. Chem. 2018, 14, 756–771, doi:10.3762/bjoc.14.64

• homogenate. Results and Discussion Synthesis of oxime bond-linked GnRH-III–[4Ser/Lys(Bu), 6Aaa, 8Lys(Dau=Aoa)] bioconjugates The GnRH-III bioconjugates were prepared as shown in Scheme 1. All peptides were synthesized by standard Fmoc-SPPS using orthogonal lysine protecting groups. Fmoc-Lys(Dde)-OH was

• aminooxyacetic acid as “carbonyl capture” reagent (2 h, at room temperature (rt)) resulted in the simultaneous removal of the side chain protecting groups and the cleavage of the peptide from the resin [54]. Peptides were isolated by precipitation with ice-cold Et2O, centrifuged, washed 3 times, dissolved in

Synthesis of a sucrose-based macrocycle with unsymmetrical monosaccharides "arms"

• Karolina Tiara,
• Mykhaylo A. Potopnyk and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2018, 14, 634–641, doi:10.3762/bjoc.14.50

• practical reasons, the method was elaborated for the methylated derivatives of hextitol pendants it might be, eventually, applied also for synthons with other protecting groups. Experimental General The NMR spectra were recorded with a Varian VNMRS 600 MHz spectrometer for solutions in CDCl3 at 25 °C. The

High-yielding continuous-flow synthesis of antimalarial drug hydroxychloroquine

• Eric Yu,
• Hari P. R. Mangunuru,
• Nakul S. Telang,
• Caleb J. Kong,
• Jenson Verghese,
• Stanley E. Gilliland III,
• Saeed Ahmad,
• Raymond N. Dominey and
• B. Frank Gupton

Beilstein J. Org. Chem. 2018, 14, 583–592, doi:10.3762/bjoc.14.45

• synthesis of the antimalarial drug hydroxychloroquine (HCQ). Key improvements in the new process include the elimination of protecting groups with an overall yield improvement of 52% over the current commercial process. The continuous process employs a combination of packed bed reactors with continuous

Addition of dithi(ol)anylium tetrafluoroborates to α,β-unsaturated ketones

• Yu-Chieh Huang,
• An Nguyen,
• Simone Gräßle,
• Sylvia Vanderheiden,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2018, 14, 515–522, doi:10.3762/bjoc.14.37

• dithiolane and dithiane protecting groups which are irreplaceable intermediates for the introduction of, e.g., fluorine via gem-difluorination [1][2]. They also allow the formation of valuable building blocks that can be used for diverse transformations in organic chemistry (e.g., Umpolung) [3]. Ketene 1,3

Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing

• Françoise Debart,
• Christelle Dupouy and
• Jean-Jacques Vasseur

Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32

• use of photolabile protecting groups [38] of allyloxycarbonyl groups deprotected by Pd(0) [39] and of fluoride-labile groups [40] in place of the standard acyl protection of nucleobases has made possible the acquisition of short sequences of heteropolymer pro-oligonucleotides. However, none of these

• to their rapid removal under mild conditions [57]. Heat-sensitive phosphate/thiophosphate-protecting groups have been incorporated into ONs via phosphoramidite chemistry using solid-support methodology. However, some required more drastic conditions (90 °C for a long period of time) to be cleaved

• potential immunotherapeutic prodrugs [58]. The first impressive result was obtained in vivo with a CpG ODN (CpG ODN fma1555) functionalized with the 2-(N-formyl-N-methyl)aminoethyl (fma) thiophosphate protecting groups, which were cleaved at 37 °C to yield the well-known immunomodulatory CpG ODN 1555

Synthetic and semi-synthetic approaches to unprotected N-glycan oxazolines

• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 416–429, doi:10.3762/bjoc.14.30

• sugars as substrates presents some limitations, as any remaining protecting groups must be removed in a subsequent step. Firstly, and most importantly, glycosyl oxazolines are extremely labile to acidic hydrolysis, and so this approach precludes the use of any OH-protecting groups that require acidic

• conditions for their cleavage. Secondly some glycosyl oxazolines are also prone to reductive cleavage by catalytic hydrogenation [41], presenting a significant further limitation as to which OH-protecting groups may be employed. Most of the reports in the literature have therefore used a protecting group

• of the 3-branched arm. Subsequent removal (or regioselective reductive ring-opening) of the 4,6-benzylidene protecting group allowed a second glycosylation at position 6. Conversion of all OH-protecting groups to acetate and the phthalamide to acetamide was followed by oxazoline formation using TMSBr

Preparation of trinucleotide phosphoramidites as synthons for the synthesis of gene libraries

• Ruth Suchsland,
• Bettina Appel and
• Sabine Müller

Beilstein J. Org. Chem. 2018, 14, 397–406, doi:10.3762/bjoc.14.28

• gene libraries stands out as facilitating fully controlled total or partial randomization at any predefined number and position of codons of a given gene. Trinucleotide synthons need to be chemically synthesized. Here, the challenge has been to find a suitable set of orthogonal protecting groups that

• ]. A key issue in all these methodologies is that the 5'- or the 3'-O-protecting group is selectively cleaved, whereas all other protecting groups (at the nucleobases, the phosphorous and the 5'- or alternatively 3'-OH group) remain intact. Basically, this aim has been achieved, although in particular

• in earlier reports a number of problems associated with insufficient stability of protecting groups under synthesis conditions, as well as restricted orthogonality have been described, which was mirrored in the sometimes severely limited quality of the trinucleotide synthons and accordingly of the

Novel amide-functionalized chloramphenicol base bifunctional organocatalysts for enantioselective alcoholysis of meso-cyclic anhydrides

• Lingjun Xu,
• Shuwen Han,
• Linjie Yan,
• Haifeng Wang,
• Haihui Peng and
• Fener Chen

Beilstein J. Org. Chem. 2018, 14, 309–317, doi:10.3762/bjoc.14.19

• . Different protecting groups for the nitrogen at the C-2 position and oxygen at C-3 are also investigated to yield the desired chiral catalysts using a simple procedure. With various bifunctional catalysts in hand, assessment of their catalytic behavior in enantioselective alcoholysis of meso-cyclic

• reactivity with this electron-poor 7i suggested that the pKa is crucial for this catalysis. Further modifications of the chloramphenicol skeleton with various protecting groups on the nitrogen at C-2 position and oxygen at C-3 did not improve the reaction but with lowered enantioselectivity (Table 1, entries

Progress in copper-catalyzed trifluoromethylation

• Guan-bao Li,
• Chao Zhang,
• Chun Song and
• Yu-dao Ma

Beilstein J. Org. Chem. 2018, 14, 155–181, doi:10.3762/bjoc.14.11

• trifluoromethyl radical was generated from CF3SO2Na in the presence of TBHP at room temperature using a mixture of water and DCM as solvent. Arylboronic acids with electron-donating substituents proceeded smoothly to give the corresponding products in good yields. Common hydroxy protecting groups (Bn and TBS

Fluorescent nucleobase analogues for base–base FRET in nucleic acids: synthesis, photophysics and applications

• Mattias Bood,
• Sangamesh Sarangamath,
• Moa S. Wranne,
• Morten Grøtli and
• L. Marcus Wilhelmsson

Beilstein J. Org. Chem. 2018, 14, 114–129, doi:10.3762/bjoc.14.7

• or 2-aminophenol afforded compounds 5 and 6, respectively. Refluxing 5 with t-BuOK in EtOH generated 7 in 38% isolated yield. When 6 was treated with the same cyclization conditions as 5 only dehalogenation was observed. Compound 8 was obtained by first removing the acetyl protecting groups using

• , the oxo-analogue tCO, which Lin et al. initially prepared in 1995 [41], was re-synthesized in order to characterize its photophysical properties, using the same procedure except that p-toluoyl protecting groups rather than acetyl were used [31]. In 2009, we published the first base–base FRET system

• yields, was effectively obtained in 86% yield by using an excess of KF in ethanol and microwave heating at 140 °C. Conveniently, at the same time all the three acetyl protecting groups were cleaved and the free nucleobase was isolated via precipitation. A 5´-DMTr protection followed by 2´-TBDMS

Stereochemical outcomes of C–F activation reactions of benzyl fluoride

• Neil S. Keddie,
• Pier Alexandre Champagne,
• Justine Desroches,
• Jean-François Paquin and
• David O'Hagan

Beilstein J. Org. Chem. 2018, 14, 106–113, doi:10.3762/bjoc.14.6

• years, there has been an increasing interest in C–F bond activation [2], with a view to using organic bound fluoride as a leaving group in substitution reactions that typically require more activated leaving groups. Such an approach could circumvent the requirement for protecting groups in multistep

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

• comprising lipid A and describes the synthesis and immunobiological properties of representative lipid A variants corresponding to different bacterial species. The main criteria for the choice of orthogonal protecting groups for hydroxyl and amino functions of synthetically assembled β(1→6)-linked

• fluoride required an excess of Lewis acid as promotor which was incompatible with the acid-labile protecting groups present in the key diglucosamine precursor. Therefore, a new N-phenyltrifluoroacetimidate Kdo donor 35 was developed (Scheme 4) [21]. The disaccharide acceptor 34 was prepared by

• regioselectively phosphorylated in a stereoselective manner by 1-O-lithiation with LHMDS, and subsequent treatment with tetrabenzyl pyrophosphate at −78 °C. Protecting groups were removed by hydrogenolysis on Pd-black to give H. pylori lipid A 39. For the synthesis of Kdo-lipid A 41 entailing a phosphoethanolamine

Synthetic mRNA capping

• Fabian Muttach,
• Nils Muthmann and
• Andrea Rentmeister

Beilstein J. Org. Chem. 2017, 13, 2819–2832, doi:10.3762/bjoc.13.274

• (rt, 24 h) and TBDMS protecting groups were removed with HCl (pH 2, rt, 12 h). (B) Large-scale production of RNAs with cap0 or cap1 by a combination of solid-phase synthesis and enzymatic methylation [111]. Deprotection conditions: DBU (1,8-diazadicyclo[5,4,0]undec-7-ene) in acetonitrile (rt, 3 min

Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• free alcohol which was oxidized to provide the N-protected dipeptide isostere 9. Some limitations were observed towards the compatibility of the N-protecting groups and in particular, N-tert-butoxycarbonyl-protected amines were not compatible with this methodology. Xaa-ψ[CF=CH]-Gly To access Xaa-ψ[CF

A semisynthesis of 3'-O-ethyl-5,6-dihydrospinosyn J based on the spinosyn A aglycone

• Kai Zhang,
• Shenglan Liu,
• Anjun Liu,
• Hongxin Chai,
• Jiarong Li and
• Lamusi A

Beilstein J. Org. Chem. 2017, 13, 2603–2609, doi:10.3762/bjoc.13.257

• opportunities to synthesize spinosyn analogues and rhamnose derivatives. Keywords: 3-O-ethyl-2,4-di-O-methylrhamnose; protecting groups; semisynthesis; spinetoram; spinosyn A; Introduction Spinosyns, a large family of secondary metabolites produced by aerobic fermentation of Saccharopolyspora spinosa, are a

• ). Rhamnose contains several hydroxy groups with similar chemical activities, so regioselective protection and alkylation are challenges. Common protecting groups of the hydroxy group at 1-position of rhamnose include allyl [28], methoxyphenyl [29] and 1-thiorhamnoside [30]. Compared with the reaction

• conditions of the other two protecting groups, the conditions of selective allyl protection are mild, and no irritant gas is produced during the reaction, so selective allyl protection was chosen to afford 1. A survey of literature [31][32][33] shows that the combination of Bu2SnO and EtBr can selectively

Diosgenyl 2-amino-2-deoxy-β-D-galactopyranoside: synthesis, derivatives and antimicrobial activity

• Henryk Myszka,
• Patrycja Sokołowska,
• Agnieszka Cieślińska,
• Andrzej Nowacki,
• Maciej Jaśkiewicz,
• Wojciech Kamysz and
• Beata Liberek

Beilstein J. Org. Chem. 2017, 13, 2310–2315, doi:10.3762/bjoc.13.227

• . This procedure removes the TCP and acetyl protecting groups in a one-pot reaction and yields diosgenyl 2-amino-2-deoxy-β-D-galactopyranoside (4). Saponin 4 treated with the HCl in MeOH was converted into hydrochloride 5. To explore the influence of different modifications of the amino group in 4 on its

Peptide synthesis: ball-milling, in solution, or on solid support, what is the best strategy?

• Ophélie Maurin,
• Pascal Verdié,
• Gilles Subra,
• Frédéric Lamaty,
• Jean Martinez and
• Thomas-Xavier Métro

Beilstein J. Org. Chem. 2017, 13, 2087–2093, doi:10.3762/bjoc.13.206

• , thereby leading to a lower overall conversion [14]. The removal of the protecting groups was performed by treatment of the Boc-protected peptides with gaseous HCl in the absence of solvents, providing the amino esters as hydrochlorides in high yield and purity (Scheme 1). Alternatively, removal of the Boc

Intramolecular glycosylation

• Xiao G. Jia and
• Alexei V. Demchenko

Beilstein J. Org. Chem. 2017, 13, 2028–2048, doi:10.3762/bjoc.13.201

• that affected the removal of the template and all benzyl protecting groups followed by acetylation of the resulting hydroxy groups. Peptide tether/template Short peptide chains have also been investigated as templates for glycosylation. The general underpinning idea is to streamline the oligosaccharide

• -selectivity. With the varying anomeric stereoselectivities and yields, it was hypothesized that the benzylic methylene group may be responsible for the increased rotational freedom between the triazoyl and benzyl moieties. Investigations with o-azidobenzyl protecting groups were used to reduce the degrees of

1,3-Dibromo-5,5-dimethylhydantoin as promoter for glycosylations using thioglycosides

• Fei-Fei Xu,
• Claney L. Pereira and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2017, 13, 1994–1998, doi:10.3762/bjoc.13.195

• of their aglycons (SEt or STol). This promoter is compatible with most commonly used protecting groups, except some electron-rich groups like 4-methoxybenzyl ethers that may be partly brominated under these conditions [40]. To probe the scope of DBDMH/TfOH-mediated 1,2-cis-glycosylation

• inexpensive reagent DBDMH has been demonstrated to be a powerful promoter for the activation of thioglycosides. This promoter is readily available, highly soluble, and shelf-stable. A variety of substrates containing diverse protecting groups have been investigated with promising results, while the