Asymmetric Michael addition reactions catalyzed by calix[4]thiourea cyclohexanediamine derivatives

• Zheng-Yi Li,
• Hong-Xiao Tong,
• Yuan Chen,
• Hong-Kui Su,
• Tangxin Xiao,
• Xiao-Qiang Sun and
• Leyong Wang

Beilstein J. Org. Chem. 2018, 14, 1901–1907, doi:10.3762/bjoc.14.164

• , were obtained. Of note, for the preparation of compound 1 the chiral mono-Boc-protected cyclohexanediamine was used for the coupling reaction. The protecting group was removed by treatment with CF3COOH to afford 1. Moreover, in order to comparatively study the role of the cavity of calix[4]arene, we

Diazirine-functionalized mannosides for photoaffinity labeling: trouble with FimH

• Femke Beiroth,
• Tomas Koudelka,
• Thorsten Overath,
• Stefan D. Knight,
• Andreas Tholey and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1890–1900, doi:10.3762/bjoc.14.163

• from p-nitrophenyl α-D-mannopyranoside (1), which was first reduced to the corresponding amine 6 [26][27] by catalytic hydrogenation (Scheme 1). HATU-mediated peptide coupling with Boc-protected glycine under basic conditions led to 7. After removal of the Boc protecting group using trifluoroacetic

• the squaric acid monoester 10 employing squaric acid diester 9. The monoester 10 was reacted with N-Boc-ethylendiamine to obtain the squaric acid diamide 11. Then removal of the Boc protecting group with trifluoroacetic acid followed by peptide coupling with the diazirine 8 led to target molecule 4

Recent advances in hypervalent iodine(III)-catalyzed functionalization of alkenes

• Xiang Li,
• Pinhong Chen and
• Guosheng Liu

Beilstein J. Org. Chem. 2018, 14, 1813–1825, doi:10.3762/bjoc.14.154

• , the selected protecting group can be removed easily under reducing conditions, providing the free diamine derivatives. However, the substrate scope was limited to alkenes bearing phenyl substituents on the backbone. On the contrary, the intermolecular diamination of alkenes presented a big challenge

An amine protecting group deprotectable under nearly neutral oxidative conditions

• Shahien Shahsavari,
• Chase McNamara,
• Mark Sylvester,
• Emily Bromley,
• Savannah Joslin,
• Bao-Yuan Lu and
• Shiyue Fang

Beilstein J. Org. Chem. 2018, 14, 1750–1757, doi:10.3762/bjoc.14.149

• . Deprotection was performed by oxidation followed by treating with a weak base. The yields were good to excellent. The new amino protecting group offers a different dimension of orthogonality in reference to the commonly used amino protecting groups in terms of deprotection conditions. It is expected to allow a

• collection of transformations to be carried out on the protected substrates that are unattainable using any known protecting groups. Keywords: amine; carbamate; dM-Dmoc; oxidation; protecting group; Introduction In multistep organic synthesis, amino groups usually have to be protected [1]. Protecting

• carboxylic acid protection [19]. To further explore the use of the 1,3-dithiane function as protecting group in organic synthesis, here we report the results of our studies on the use of the dimethyl-1,3-dithian-2-ylmethoxycarbonyl (dM-Dmoc) group for amine protection (Scheme 1). Compared with the Dmoc group

Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

• the reaction outcome, favoring nucleophilic attack from a preferred face of the sugar ring [22][23]. Grynkiewicz and colleagues have discussed anchimeric assistance even when no protecting group is present at C-2, assuming a Brigl’s anhydride type intermediate [24]. In the absence of a substituent at

• bulky DTBS protecting group to enforce α-stereoselection despite of the anchimeric effect of the vicinal N-Troc protecting group to achieve the α-glycoside 80 in high yield. Nevertheless, this reaction needed optimization, such as an unusually high reaction temperature. Also weakly acidic phenols were

• ]. Synthesis of phenyl glycosides 44 and 45 from unprotected sugars [24]. Synthesis of azobenzene mannosides 47 and 48 without protecting group chemistry [46]. Synthesis of various aryl sialosides using Mitsunobu glycosylation [25]. Mitsunobu synthesis of different jadomycins [54][55]. BOM: benzyloxymethyl

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

• adjacent to a sulfur atom, which affects the regioselectivity of the reaction. To study the effects of a protecting group on the reaction, the regioselectivity of the reaction was examined using 42 and 43, which were obtained from 27. When the 5-hydroxy group was protected with a benzoyl group, the

• coupling reaction of 42 occurred at the 4-position, as in the case mentioned above, to give 46 in 44% yield along with the desired product and its N7 isomer. In contrast, switching the protecting group of 27 at the 5-position to TBS resulted in the exclusive formation of 45 reacted at the 1-position (28

Oligonucleotide analogues with cationic backbone linkages

• Melissa Meng and
• Christian Ducho

Beilstein J. Org. Chem. 2018, 14, 1293–1308, doi:10.3762/bjoc.14.111

• protecting group to yield the free 5'-amine 34. Subsequent iterative coupling–deprotection cycles resulted in the formation of the guanidinium-linked oligomer 35. After basic guanidine and purine deprotection and concomitant cleavage from the solid support, final acidic deprotection furnished A5T

Stereoselective nucleophilic addition reactions to cyclic N-acyliminium ions using the indirect cation pool method: Elucidation of stereoselectivity by spectroscopic conformational analysis and DFT calculations

• Koichi Mitsudo,
• Junya Yamamoto,
• Tomoya Akagi,
• Atsuhiro Yamashita,
• Masahiro Haisa,
• Kazuki Yoshioka,
• Hiroki Mandai,
• Koji Ueoka,
• Christian Hempel,
• Jun-ichi Yoshida and
• Seiji Suga

Beilstein J. Org. Chem. 2018, 14, 1192–1202, doi:10.3762/bjoc.14.100

• protocol [12] (see Supporting Information File 1). As observed in our previous studies, the Boc protecting group was found not suitable for the direct cation pool method due to its cleavage by protic acid generated during the electrolysis of the cation precursor. However, it can be utilized in the indirect

Recyclable hypervalent-iodine-mediated solid-phase peptide synthesis and cyclic peptide synthesis

• Dan Liu,
• Ya-Li Guo,
• Jin Qu and
• Chi Zhang

Beilstein J. Org. Chem. 2018, 14, 1112–1119, doi:10.3762/bjoc.14.97

• test whether the FPID/(4-MeOC6H4)3P system can be used in SPPS. We selected the commercially available 2-chlorotrityl chloride resin (2-Cl-Trt-Cl resin) as the solid support and [(9-fluorenylmethyl)oxy]carbonyl (Fmoc) as the α-amino protecting group. The peptides were synthesized following the route as

• D following the same cyclization strategy mentioned above by direct coupling of the precursor 2 without any protecting group utilizing the system of FPID/(4-MeOC6H4)3P (Scheme 4, method C). We have obtained the precursor 2 through SPPS mediated by FPID/(4-MeOC6H4)3P system (Table 1, entry 2

• coupling reagent, which was developed by Ye’s group in order to reduce racemization and side reactions [50]. The precursor 2 was obtained via successive deprotection of the C-terminal and the N-terminal protecting group of 14. The overall yield of this route is 28%. With the precursor 2 in hand, we then

Synthetic avenues towards a tetrasaccharide related to Streptococcus pneumonia of serotype 6A

• Aritra Chaudhury,
• Mana Mohan Mukherjee and
• Rina Ghosh

Beilstein J. Org. Chem. 2018, 14, 1095–1102, doi:10.3762/bjoc.14.95

• ) glycosylation for our synthesis. Two different strategies were attempted in this direction. Recently, Mong et al. have reported high α-selectivity in the formation of glucan and galactan under non-participating conditions from the O-2 protecting group [39][40]. With this method, we tried to couple donor p-tolyl

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

• solution (Figure 1B vs 1A) the compounds could be obtained in higher yields compared to the control (K). Isopropylidene protected aminooxyacetyl moiety was used to avoid unwanted reactions with aldehydes or ketones. This protecting group was removed with 1 M methoxylamine in 0.2 M NH4OAc solution (pH 5.0

• protecting group was achieved by using 2% TFA in DCM for 6 × 4 min. The coupling of the isopropylidene protected aminooxyacetic acid [17] to the N-terminus of the linker sequence was carried out by using standard protocol DIC/HOBt coupling. The cleavage from the solid support was performed at rt in a

Bromide-assisted chemoselective Heck reaction of 3-bromoindazoles under high-speed ball-milling conditions: synthesis of axitinib

• Jingbo Yu,
• Zikun Hong,
• Xinjie Yang,
• Yu Jiang,
• Zhijiang Jiang and
• Weike Su

Beilstein J. Org. Chem. 2018, 14, 786–795, doi:10.3762/bjoc.14.66

• -selectivity under 700 rpm, giving 6-bromo-substituted product 3da in 94% yield. Indazoles with N-Me, THP and Bn groups afforded good to excellent yields in the coupling reaction with n-butyl acrylate. However, the N-Boc substrate readily underwent removal of the protecting group [65], and resulted in the

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

• ) [74]. Protected D-ribonolactone 27 was treated with lithiated pyridine to obtain lactol 28 (Figure 10B). Deoxygenation and reduction gave 29, wherein the isopropylidene group was also removed. Conversion of the cyano to an amide group, followed by removal of the silyl protecting group gave 24, which

• 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 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

• (19) readily available by a selective silylation of 1’,2,3,3’,4,4’-hexa-O-benzylsucrose (7) [36]. Aldehyde 20 [37] – obtained by Swern oxidation [38] of alcohol 19 – was reacted with amine 17 to afford the desired amine isolated as acetate 21 in 85% total yield. Removal of the TBDPS protecting group

Enzyme-free genetic copying of DNA and RNA sequences

• Marilyne Sosson and
• Clemens Richert

Beilstein J. Org. Chem. 2018, 14, 603–617, doi:10.3762/bjoc.14.47

• , the 3'-amine was protected with an azidomethyloxycarbonyl (Azoc) protecting group. This protecting group can be rapidly removed under non-denaturing conditions after incorporation by the complementary nucleotide using the Staudinger reaction with a water-soluble phosphine (Figure 11). This protocol

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

• the 2’-O-tert-butyldithiomethyl-protecting group [18]. In the recent approach, the MDTM modification was obtained in excellent yield after conversion of the 2,4,6-trimethoxybenzylthiomethyl precursor group by treatment with dimethyl(methylthio)sulfonium tetrafluoroborate (DMTSF, Scheme 2). First, ONs

• and 2-cyano-2-(2-phenylethylaminocarbonyl)-3-(pivaloyloxy)propyl groups (Figure 1A and 1B) [41]. Indeed, this work also did not lead to ONs for use in control of gene expression. In addition, Lönnberg described the 4-acetylthio-2,2-dimethyl-3-oxobutyl group as another phosphate protecting group that

• because the seed region is crucial for the recognition of mRNA target but does not affect the cleavage site (Scheme 20D). Two protected nucleotides in a siRNA totally prevented RNAi that is “turned on” after UV irradiation. Thus, the NPOM-protecting group induces reversible inactivation of siRNAs

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

• for any further protecting group manipulations, and simplifying synthetic strategies. As an alternative to total synthesis, significant quantities of several structurally complicated N-glycans can be isolated from natural sources, such as egg yolks and soy bean flour. Enzymatic transformations of

• 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

• 2009) was therefore to perform all protecting group manipulations/interconversions on the completed oligosaccharide to ensure that all OH groups were protected as base-labile esters, before oxazoline formation. In 2009, Shoda published [42] a paper that was to completely change the way in which

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

• . Preparation of trinucleotides in solution Over the years, a number of methodologies has been published, varying in the protecting group for the phosphate moiety being methyl [25], ethyl [26], cyanoethyl [27] or ortho-chlorophenyl [28][29], and for the 3'-OH-group being phenoxyacetyl [25], dimethoxytrityl

• ]. 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

• ][27][29], and is easily achieved with trimers having o-chlorophenyl groups for protection of the phosphate moiety [22][29]. However, phosphitylation becomes a crucial step, if β-cyanoethyl is used as the phosphate protecting group [27]. Using 2-cyanoethyl-N,N-diisopropylchlorophosphoramidite for

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

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

• starting from azide 1 by first protecting the 3-OH group with an allyloxycarbonyl (Alloc) protecting group followed by regioselective reductive opening of the 4,6-O-benzylidene acetal using NaCNBH3 and HCl in diethyl ether, and successive phosphitylation of the liberated 4’-OH functionality with N,N

• DBU to provide a free amino group, the 2’-NH2 and 3-OH groups could be differentiated in the next acylation step by using DCC as activating agent for the N-acylation, and Steglich reaction conditions (DCC and DMAP) for the O-acylation. Following removal of the Alloc protecting group was readily

• separation of the anomeric α/β mixture furnished the anomerically pure trisaccharide 15. Next, three acyl residues were introduced at positions 2’, 3’ and 3 by successive deprotection–acylation sequence. The N-Fmoc protecting group was removed using DBU and the resulting free amino group was acylated with (R

The synthesis of the 2,3-difluorobutan-1,4-diol diastereomers

• Robert Szpera,
• Nadia Kovalenko,
• Kalaiselvi Natarajan,
• Nina Paillard and
• Bruno Linclau

Beilstein J. Org. Chem. 2017, 13, 2883–2887, doi:10.3762/bjoc.13.280

• protecting group resulted in a significant increase in mass, and therefore, chromatographic purification of the protected intermediates upon scale-up was inconvenient. As previously reported [17], epoxide opening of cis-2 with Olah’s reagent (HF·py) led to an 80% yield of the fluorohydrin after just three

• procedure is deemed to have low risk. Nonetheless, care must be taken and the reaction was run with the protection of a blast shield. In order to reduce the relative contribution of the protecting group to the overall weight of the intermediates, the use of an acetonide was explored. Given the starting

• increase). An investigation to use the much smaller acetonide protecting group, which can be used for the cis-1,4-butenediol starting material, was carried out. It was found that the use of Et3N·3HF for the epoxide opening step also lead to acetal rearrangement, leading to a more stable 1,3-dioxolane ring

Position-dependent impact of hexafluoroleucine and trifluoroisoleucine on protease digestion

• Susanne Huhmann,
• Anne-Katrin Stegemann,
• Kristin Folmert,
• Damian Klemczak,
• Johann Moschner,
• Michelle Kube and
• Beate Koksch

Beilstein J. Org. Chem. 2017, 13, 2869–2882, doi:10.3762/bjoc.13.279

• support by means of an Fmoc/tert-butyl protecting group strategy on a preloaded Fmoc-Lys(Boc)Wang resin (0.57 mmol/g loading) using 10 mL polypropylene reactors. HfLeu containing peptides were synthesized with an Activo-P11 automated peptide synthesizer (Activotec, Cambridge, United Kingdom). Couplings of

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

• the resulting amine 18, cleavage of the alcohol protecting group, Jones oxidation and formation of the methyl ester afforded the corresponding dipeptide isostere Boc-Ser(PMB)-ψ[(Z)-CF=CH]-Gly-OMe (19). In the same way, Boc-Val-ψ[(Z)-CF=CH]-Gly-OMe, Boc-Leu-ψ[(Z)-CF=CH]-Gly-OMe and Boc-Ala-ψ[(Z)-CF=CH

• = 75:25). Further modifications (removal of the sulfinyl group and the silyl protecting group in acidic conditions, transformation of the amine in methyl carbamate and oxidation of the primary alcohol into the corresponding carboxylic acid) gave the final isostere 93. In 2013, Pannecoucke and co

• -workers proposed a new strategy based on a chemoenzymatic reduction of ethyl 2-oxocyclopentanecarboxylate (94) using Baker’s yeast to afford the corresponding chiral alcohol 95 (Scheme 19) [53]. Then, reduction of the ester into the primary alcohol, its selective protection by a silyl protecting group

Consecutive hydrazino-Ugi-azide reactions: synthesis of acylhydrazines bearing 1,5-disubstituted tetrazoles

• Angélica de Fátima S. Barreto,
• Veronica Alves dos Santos and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2017, 13, 2596–2602, doi:10.3762/bjoc.13.256

• chose hydrazine tetrazole 10j to continue the synthesis, as it was obtained in excellent yield, it shows distinct NMR spectra and offers the possibility of further functionalization after removal of the Boc protecting group. Therefore, compound 10j was subjected to hydrazinolysis with hydrazine

Asymmetric synthesis of propargylamines as amino acid surrogates in peptidomimetics

• Matthias Wünsch,
• David Schröder,
• Tanja Fröhr,
• Lisa Teichmann,
• Sebastian Hedwig,
• Nils Janson,
• Clara Belu,
• Jasmin Simon,
• Shari Heidemeyer,
• Philipp Holtkamp,
• Jens Rudlof,
• Lennard Klemme,
• Alessa Hinzmann,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2017, 13, 2428–2441, doi:10.3762/bjoc.13.240

• propargylamines 7 in high yields and satisfactory diastereomeric ratios by cleaving off the TMS protecting group with TBAF. In previous investigations, the choice of solvent and Lewis acid were controversially discussed [13][14][45][46][47][48][49][50][52][53][54][55]. Nonpolar solvents (DCM < THF < Et2O

Fluorination of some highly functionalized cycloalkanes: chemoselectivity and substrate dependence

• Attila Márió Remete,
• Melinda Nonn,
• Santos Fustero,
• Matti Haukka,
• Ferenc Fülöp and
• Loránd Kiss

Beilstein J. Org. Chem. 2017, 13, 2364–2371, doi:10.3762/bjoc.13.233

• behavior in fluorination in view of selectivity and to explore substrate dependency and chemodifferentiation. Based on the different stereochemical structures of the selected model diols as well as the nature of the N-protecting group used, we expected differences in their chemical behavior under

• -membered diol stereoisomers (±)-1 and (±)-4 proved to be highly substrate dependent and on the basis of our earlier findings on substrate determinant fluorinations [37], we next investigated the effect of the nature of the N-protecting group on this reaction. The treatment of N-Cbz-protected dihydroxylated

• amide intermediate T17 which undergoes an intramolecular cyclization to give (±)-17 (Scheme 8). A similar aziridinium opening reaction with fluoride can be found in [38][39]. Interestingly, when changing the N-protecting group from benzoyl in (±)-14 to Cbz ((±)-18), the fluorination with Deoxofluor