Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• or tributyltin cyanides and the stereochemical outcome of these reactions strongly depends on the protecting group. Diastereoisomeric excesses of 60–80% were observed in the cyanation of tert-butyldimethylsilyl ether 107a and 108a was the major product, while for the acetate 107b the selectivity was

• groups were removed by concentrated acid. A very efficient synthesis of (2S,3S,4S)-4 starts from another serine-derived chiron, namely O-benzyl-N-Boc-D-serine [111], which was readily transformed to the Z-olefin 120 containing a benzophenone imine residue as a nitrogen protecting group (Scheme 29

• -phenylfluorenyl protecting group was installed to prevent racemization and oxidation allowed to introduce the C=C bond leading to 3,4-didehydroglutamate (S)-126. Asymmetric dihydroxylation of (S)-126 (ee 96%) gave (2S,3S,4R)-127 (de 94%). Synthetic applications of enantiomeric hydroxy-L-glutamic acids Besides

Unexpected loss of stereoselectivity in glycosylation reactions during the synthesis of chondroitin sulfate oligosaccharides

• Teresa Mena-Barragán,
• José L. de Paz and
• Pedro M. Nieto

Beilstein J. Org. Chem. 2019, 15, 137–144, doi:10.3762/bjoc.15.14

• positions 4 and 6 of GalNAc units favor the formation of 1,2-cis glycosidic bonds, even in the presence of 2-participating groups [43][44]. Treatment with (HF)n·Py complex in THF followed by standard acetylation provided compound 7. This derivative displayed a suitable protecting group distribution for the

• the glycosylation outcome, we decided to prepare 2,3-di-O-pivaloyl compound 26 with the GlcA protecting group distribution used in this study. For this purpose, donor 3 was glycosylated with 4-methoxyphenol and then treated with hydrazine monohydrate in a pyridine/acetic acid/CH2Cl2 mixture to afford

6’-Fluoro[4.3.0]bicyclo nucleic acid: synthesis, biophysical properties and molecular dynamics simulations

• Sibylle Frei,
• Andrei Istrate and
• Christian J. Leumann

Beilstein J. Org. Chem. 2018, 14, 3088–3097, doi:10.3762/bjoc.14.288

• -ROESY experiments (Supporting Information File 1). The gem-difluorinated tricyclic nucleoside 12β was then converted into the bicyclic fluoroenone 13 via desilylation and ring-enlargement by short exposure to HF-pyridine. During the following Luche reduction of derivative 13 the benzoyl protecting group

Synthesis of pyrrolidine-based hamamelitannin analogues as quorum sensing inhibitors in Staphylococcus aureus

• Jakob Bouton,
• Kristof Van Hecke,
• Reuven Rasooly and
• Serge Van Calenbergh

Beilstein J. Org. Chem. 2018, 14, 2822–2828, doi:10.3762/bjoc.14.260

• -propanediol (16), which was selectively monoprotected in high yield as TBS ether (Scheme 3) [25]. The remaining alcohol was then substituted for a phthalimide via Mitsunobu reaction. Phthalimide deprotection, acylation with benzoic acid, and removal of the silyl protecting group furnished 10. Fragments 9 and

• only in an elimination product. This led us to replace the electron-withdrawing nosyl protecting group with a Boc group. After removal of the TBS ether and mesylation of the resulting alcohol, substitution with NaN3 now smoothly provided azide 29. The azide was then reduced under classical Staudinger

Synthesis of α-D-GalpN₃-(1-3)-D-GalpN₃: α- and 3-O-selectivity using 3,4-diol acceptors

• Emil Glibstrup and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2018, 14, 2805–2811, doi:10.3762/bjoc.14.258

• be synthesized in 4 less steps than otherwise required. These results show, how the desired protecting group pattern can direct which glycosylation strategy to choose: In the less sterically hindered cases, a 4-O-protecting group, such as the benzoyl or benzyl, can be preferable. However, when a

• and readily available building block. Challenging the α,3-O-selectivity with the different 6-O-protecting group variants. Representative glycosylations with closely related systems [34][44]. Capping the free 4-OH, allowing for easier separation of mixtures obtained during glycosylation

Novel solid-phase strategy for the synthesis of ligand-targeted fluorescent-labelled chelating peptide conjugates as a theranostic tool for cancer

• Sagnik Sengupta,
• Mena Asha Krishnan,
• Premansh Dudhe,
• Ramesh B. Reddy,
• Bishnubasu Giri,
• Sudeshna Chattopadhyay and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2018, 14, 2665–2679, doi:10.3762/bjoc.14.244

• ) amino protecting group before attachment of fluorescent tag with the peptidic spacer. This results in premature cleavage of the peptide chain and loss of chemical yield during the bioconjugate synthesis. Further, attaching a radiotracer chelating core containing acid sensitive functional groups and the

• acid attached to chlorotrityl resin via dipeptide intermediate 6 to give the tripeptide intermediate 7. The tripeptide 7 was then attached to strategic lysine amino acid, Fmoc-Lys-(Pg)-OH, whose ε-amino group is protected as either an Mtt (4-methyltrityl) or an Mmt (4-methoxytrityl) protecting group

• the Mtt protecting group was achieved when 9a was treated with either 1% TFA in dichloromethane or a mixture of acetic acid/trifluoroethanol/DCM in 1:2:7 ratio for 1 h at room temperature [43]. Unfortunately, the polypeptide chain 9a cleaved off too from the resin beads (Scheme 2). Therefore, it

The design and synthesis of an antibacterial phenothiazine–siderophore conjugate

• Abed Tarapdar,
• James K. S. Norris,
• Oliver Sampson,
• Galina Mukamolova and
• James T. Hodgkinson

Beilstein J. Org. Chem. 2018, 14, 2646–2650, doi:10.3762/bjoc.14.242

• phenothiazine 5 was isolated after removal of the Boc protecting group in TFA. Initial attempts at aqueous work-up conditions to isolate the free base resulted in lower isolated yields of 5 due to its high water solubility, and it was decided 5 would be progressed further as the TFA salt avoiding aqueous work

• . However, as our final conjugate contains an aromatic halide we wanted to avoid hydrogenation as the final step and we instead chose to use the para-methoxybenzyl (PMB) protecting group which can be removed under acidic conditions. PMB-protected benzoic acid building block 7 was prepared following a

Comparative cell biological study of in vitro antitumor and antimetastatic activity on melanoma cells of GnRH-III-containing conjugates modified with short-chain fatty acids

• Eszter Lajkó,
• Sarah Spring,
• Rózsa Hegedüs,
• Beáta Biri-Kovács,
• Sven Ingebrandt,
• Gábor Mező and
• László Kőhidai

Beilstein J. Org. Chem. 2018, 14, 2495–2509, doi:10.3762/bjoc.14.226

• peptide synthesis (SPPS) using Fmoc/t-Bu strategy with the orthogonal protecting scheme as described before [17][19] and presented in detail in Supporting Information File 1. In all cases, a Mtt (methyltrityl) protecting group was applied to block the side chain of Lys in position 8. For the development

• higher hydrazine concentration (4% in DMF) and longer treatment (12 × 5 min) for the complete removal of the protecting group. However, ivDde is more stable in circumstances (2% DBU, 2% piperidine in DMF) used for the Fmoc removal. To avoid the unwanted Dde removal during the synthesis ivDde was applied

• in this study. After acylation of the free amino group on the side chain of 4Lys using either acetic or butyric anhydride, the Mtt protecting group was detached. Though the application of bis-Boc-aminooxyacetic acid to incorporate the Aoa moiety provided better results (10–15% better yield according

Synthesis of a leopolic acid-inspired tetramic acid with antimicrobial activity against multidrug-resistant bacteria

• Luce Mattio,
• Loana Musso,
• Leonardo Scaglioni,
• Andrea Pinto,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2018, 14, 2482–2487, doi:10.3762/bjoc.14.224

• protect the oxygen at C-4 [15]. We selected a benzyl protecting group, as it could be cleaved by catalytic hydrogenation together with the benzyl ester of L-phenylalanine in the ureidodipeptide fragment (see synthesis of compound 20) by a one-pot reaction. To increase the reaction rate toward O-alkylation

Efficient catalytic alkyne metathesis with a fluoroalkoxy-supported ditungsten(III) complex

• Henrike Ehrhorn,
• Janin Schlösser,
• Dirk Bockfeld and
• Matthias Tamm

Beilstein J. Org. Chem. 2018, 14, 2425–2434, doi:10.3762/bjoc.14.220

• the ACM are summarized in Table 3. The depicted reactions selectively afforded the unsymmetrical alkynes, corroborating that the bimetallic tungsten complex W2F3 is able to introduce a trimethylsilyl protecting group to alkynes. Conclusion Previously, we have reported the optimum level of fluorination

Semi-synthesis and insecticidal activity of spinetoram J and its D-forosamine replacement analogues

• Kai Zhang,
• Jiarong Li,
• Honglin Liu,
• Haiyou Wang and
• Lamusi A

Beilstein J. Org. Chem. 2018, 14, 2321–2330, doi:10.3762/bjoc.14.207

• experimental steps, and the operations were troublesome. So an improved synthesis based on a self-protection strategy was designed and discussed. In this work, 3-O-ethyl-2,4-di-O-methylrhamnose was used as both the reaction substrate of C9–OH and the protecting group of C17–OH. The number of synthetic steps

• as the glycosylation donor of C9–OH, but also the protecting group of C17–OH, greatly reducing the synthetic steps and costs. Macrolide compounds are a new kind of insecticides and fungicides which have also been widely applied in medicine [14][15]. Currently, research on structural modification of

Synthesis of 1,4-imino-L-lyxitols modified at C-5 and their evaluation as inhibitors of GH38 α-mannosidases

• Maroš Bella,
• Sergej Šesták,
• Ján Moncoľ,
• Miroslav Koóš and
• Monika Poláková

Beilstein J. Org. Chem. 2018, 14, 2156–2162, doi:10.3762/bjoc.14.189

• be achieved via nucleophilic addition of MeMgBr to an aldehyde obtained by the oxidation of alcohol 7. Despite this fact, we did not manage the preparation of the aldehyde by the oxidation of alcohol 7 probably due to its instability [33]. However, similar aldehyde 17 bearing a Cbz protecting group

• chromatography on silica gel, the sensitive aldehyde 17 was used in the next step without further purification and characterization. Diastereoselective addition of MeMgBr to the aldehyde group of 17 gave alcohol 18 as single diastereoisomer in 69% yield. Removal of the Cbz protecting group of 18 under catalytic

• hydrogenolysis conditions furnished the free amine which was subsequently subjected to N-benzylation with the corresponding (4-halo)benzyl bromide to afford N-(4-halo)benzylpyrrolidines 19a–c. Acidic hydrolysis of the acetonide protecting group in 19a–c provided target compounds 4a–c in good yields (Scheme 3

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