The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

N-Glycosides of indigo, indirubin, and isoindigo: blue, red, and yellow sugars and their cancerostatic activity

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2840–2869, doi:10.3762/bjoc.20.240

• very good Z-selectivity. Employment of the pivaloyl instead of the acetyl protective group resulted in an improved yield for both steps to give S-glucoside β-54b. All attempts to deprotect compounds 54a,b failed. Compound 54a shows a moderate and selective activity against lung cancer cells H157 [52

N-Boc-α-diazo glutarimide as efficient reagent for assembling N-heterocycle-glutarimide diads via Rh(II)-catalyzed N–H insertion reaction

• Grigory Kantin,
• Pavel Golubev,
• Alexander Sapegin,
• Alexander Bunev and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 1841–1848, doi:10.3762/bjoc.19.136

• /lenalidomide precursor 10 with a high yield (Scheme 5). In the near future, after removal of the protective group, the biological profile of the compound obtained will be studied (i.e., antimyeloid activity, degradation of transcription factors IKZF1/2/3, antiangiogenic activity, and cytokine secretion), which

• diazocarbonyl reagent is presented for the first time. The protective group is removed without acid catalysis with near quantitative yields. New benzotriazole derivatives containing functional groups capable of participating in the subsequent modification for linker attachment to assemble the PROTAC molecule

Construction of hexabenzocoronene-based chiral nanographenes

• Ranran Li,
• Di Wang,
• Shengtao Li and
• Peng An

Beilstein J. Org. Chem. 2023, 19, 736–751, doi:10.3762/bjoc.19.54

• between compound 106 and tetracyclone 80, followed by removing the triisopropylsilane protective group using tetrabutylammonium fluoride (TBAF) provided compound 107. Then, a second Sonogashira coupling between 107 and 104 produced compound 108, followed by a second Diels–Alder reaction between 108 and 80

Site-selective reactions mediated by molecular containers

• Rui Wang and
• Yang Yu

Beilstein J. Org. Chem. 2022, 18, 309–324, doi:10.3762/bjoc.18.35

• ; microenvironment; molecular containers; noncovalent protective group; site-selectivity; Introduction To run reactions with discriminate control over product selectivity represents one of the huge challenges in organic synthetic chemistry [1], among which, site-selectivity is always crucial to a reaction when

• container as the noncovalent protective group, the Pitchumani and Srinivasan group also reported that the reduction of coumarin (18) by sodium borohydride could be site-selectively induced in the presence of β-cyclodextrin C (Figure 4c) [59]. The reduction site-selectively occurred at the carbonyl not the

• could be regarded as a protective group by shielding the internal alkenyl site. In 2016, the Rebek group achieved the site-selective reduction of an α,ω-diazide compound by trimethylphosphine (PMe3) in aqueous solution with a cavitand host as the protecting group for one of the azide sites (Figure 5

Synthesis of new pyrazolo[1,2,3]triazines by cyclative cleavage of pyrazolyltriazenes

• Nicolai Wippert,
• Martin Nieger,
• Claudine Herlan,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2021, 17, 2773–2780, doi:10.3762/bjoc.17.187

• 4,6-dihydro-3H-pyrazolo[3,4-d][1,2,3]triazines, were not successful under similar conditions due to the higher stability of the triazene functionality in the regioisomeric precursors and thus, the failure of the removal of the protective group. Keywords: cyclization; diazonium chemistry; pyrazoles

• possible, especially pyrazolotriazines with an aliphatic substituent on the pyrazole-nitrogen (5e–i) degraded rapidly in contact with air/moisture. The conversion of the regioisomeric compounds 10 to 6 failed under the conditions described in Scheme 4. The triazene protective group could not be cleaved

• added to a methylamine intermediate in step 2 and step 4 of the reaction sequence. Depending on the introduced side chain, further modifications were obtained (shown for compound 9g). The triazene protective group tolerates the reaction conditions used for the described processes and is probably

The ethoxycarbonyl group as both activating and protective group in N-acyl-Pictet–Spengler reactions using methoxystyrenes. A short approach to racemic 1-benzyltetrahydroisoquinoline alkaloids

• Marco Keller,
• Karl Sauvageot-Witzku,
• Franz Geisslinger,
• Nicole Urban,
• Michael Schaefer,
• Karin Bartel and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2716–2725, doi:10.3762/bjoc.17.183

• , also as protective group for phenolic residues. After ring closure, the ethoxycarbonyl-protected phenols are deprotected simultaneously with the further processing of the carbamate group, either following route A (lithium alanate reduction) to give N-methylated phenolic products, or following route B

• relationships in this chemotype. Keywords: acyl Pictet–Spengler reaction; alkaloids; antiproliferative activity; benzyltetrahydroisoquinolines; ion channels; protective group; total synthesis; Introduction The benzylisoquinoline alkaloids are a large and diverse class of plant secondary metabolites including

• ]. This prompted us to investigate the generality of this approach (dual function of the ethoxycarbonyl residue as activating group for the Pictet–Spengler reaction and as protective group for phenolic groups). This effort ended up with short and effective total syntheses of ten racemic 1-benzyl-1,2,3,4

Substituted nitrogen-bridged diazocines

• Pascal Lentes,
• Jeremy Rudtke,
• Thomas Griebenow and
• Rainer Herges

Beilstein J. Org. Chem. 2021, 17, 1503–1508, doi:10.3762/bjoc.17.107

• Fmoc chloride to accomplish an orthogonal protective group strategy. The removal of the Boc groups from compounds 5 with TFA gave the mixed aniline and nitro precursors 6. In previous approaches, the nitro groups were reduced to hydroxylamines with zinc and oxidized to the corresponding nitroso

An azobenzene container showing a definite folding – synthesis and structural investigation

• Abdulselam Adam,
• Saber Mehrparvar and
• Gebhard Haberhauer

Beilstein J. Org. Chem. 2019, 15, 1534–1544, doi:10.3762/bjoc.15.156

• protective group, the resulting amino acid was cyclodimerized to the benzyl-protected macrocycle. The yield for the cyclization amounts to about 50%. The last step was the removal of the benzyl group by hydrogenolysis to yield the desired macrocycle 3a. The cyclopeptide 2a [52] is commercially available

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

• bond for steric reasons. Selective removal of the silyl protective group allowed for the hydroxymethyl to carboxyl transformation to (4S,5R)-26, and hydrolysis afforded (2S,3R)-2 as the hydrochloride (Scheme 6) [55]. From homochiral aziridine An interesting approach to protected (2S,3R)-2 makes use of

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

• synthesis, we realized that the synthesis of the α-D-GalpNAc-(1-3)-β-D-GalpNAc part worked more efficiently, when using the 3,4-diol acceptor instead of a fully protected 3-OH. As some protective group manipulations can be avoided and at the same time the yield and α-selectivity improved, we consider this

• -OTBDPS as protective group (1 in Scheme 1) and benzylation with freshly prepared Ag2O and BnBr in the solvent mixture CH2Cl2/cyclohexane 1:4 as described by Wang et al. [39], a 91% isolated yield of the migrated product, i.e., 3-O-Bn, 4-O-Bz, was obtained (Scheme 1). Following the apparent difference in

• large 6-O-protective group, such as TBDPS, is used, it proves advantageous to do the glycosylation directly on the 3,4-diol. Post-glycosylation modifications, i.e., benzylation of the free 4-OH on the TBDPS–TBDPS variant 17 using standard BnBr followed by NaH resulted in a 1:1 mixture of the desired

D-Fructose-based spiro-fused PHOX ligands: synthesis and application in enantioselective allylic alkylation

• Michael R. Imrich,
• Jochen Kraft,
• Cäcilia Maichle-Mössmer and
• Thomas Ziegler

Beilstein J. Org. Chem. 2018, 14, 2082–2089, doi:10.3762/bjoc.14.182

• carbohydrate chemistry a well-known phenomenon is participation of neighboring groups. An oxocarbenium ion is often stabilized by protective groups. Esters are a class of protective groups which often participate in such a manner [43][44]. 7j–m bear at least one ester protective group. We propose that when R1

• different substitution pattern at positions 3, 4 and 5. PG: protective group, X: leaving group. Activation of 7 to oxocarbenium ion 9 in the Ritter reaction. Zemplén deacetylation of 10i. Benzylation of 10j to give 10b. Plausible mechanism of the Ritter reaction. For better clarity C-2 is not shown in

Cationic cobalt-catalyzed [1,3]-rearrangement of N-alkoxycarbonyloxyanilines

• Itaru Nakamura,
• Mao Owada,
• Takeru Jo and
• Masahiro Terada

Beilstein J. Org. Chem. 2018, 14, 1972–1979, doi:10.3762/bjoc.14.172

• methoxycarbonyl, Alloc and Cbz were tolerated as a protective group on the nitrogen atom, affording the desired products 2 in good yields (Table 3, entries 1–3). The reaction of 1e having a 2,2,2-trichloroethoxycarbonyl (Troc) group, however, resulted in decomposing 1e (Table 3, entry 4). The use of aroyl groups

• -nitrobenzyloxycarbonyl group in place of Cbz as the migrating group (Table 4, entry 11). In addition, compatibility of the protective group on the oxygen atom was tested (Table 4, entries 12–14), since it is expected that the cationic cobalt would make the protective group labile as well as the protective group would

Phosphoramidite building blocks with protected nitroxides for the synthesis of spin-labeled DNA and RNA

• Timo Weinrich,
• Eva A. Jaumann,
• Ute M. Scheffer,
• Thomas F. Prisner and
• Michael W. Göbel

Beilstein J. Org. Chem. 2018, 14, 1563–1569, doi:10.3762/bjoc.14.133

• could be incorporated by unmodified standard procedures into four different self-complementary DNA and two RNA oligonucleotides. After photochemical removal of the protective group, elimination of formic aldehyde and spontaneous air oxidation, the nitroxide radicals were regenerated in high yield. The

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

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

• microfluidic conditions applied by the authors ensured even better stereoselectivity and higher yields [21]. Sequential protective group manipulation and N-acylation procedure furnished the lipid A precursor 37. The isopropylidene and anomeric allyl groups in 37 were removed and the anomeric position in 38 was

• liberated NH2 group provided 65. A successive protective group manipulation/acylation sequence furnished tetraacylated 66. The oxidation of the primary alcohol in 66 to form the corresponding carboxylic acid was achieved by a two-step procedure involving oxidation under Swern conditions to give an

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

• low concentrations of acid under pressure, typical conditions of HPLC analysis. Consequently, the application of the tert-butylsulfinyl as protective group for the amine is restricted to very mild conditions. However, it can be easily cleaved from N-sulfinyl propargylamines by acidic methanolysis and

• assume that strong bases do not only lead to desilylation, but also induce decomposition of the propargylamine system (see below). Kracker et al. recently demonstrated the substitution of the labile tert-butylsulfinyl group of compounds 7a–c by the more versatile Boc protective group in yields of 56–94

• trifluoromethyl nucleophiles, such as TMS–CF3 [84][85] has been described to be inefficient. Still, the asymmetric synthesis of CF3-substituted propargylamines has been described, using (R)-2-methoxy-1-phenylethan-1-amine as chiral auxiliary [86][87][88]. However, cleavage of the protective group requires

Sulfation and amidinohydrolysis in the biosynthesis of giant linear polyenes

• Hui Hong,
• Markiyan Samborskyy,
• Katsiaryna Usachova,
• Katharina Schnatz and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2017, 13, 2408–2415, doi:10.3762/bjoc.13.238

• terminal amino moiety are formed by specific final-stage deamidination of a precursor bearing a guanidino substituent at this position [10]. The aim of the present study was to test whether the same "protective group" strategy is operating in the biosynthesis of the giant linear mediomycins. If true, then

Preactivation-based chemoselective glycosylations: A powerful strategy for oligosaccharide assembly

• Weizhun Yang,
• Bo Yang,
• Sherif Ramadan and
• Xuefei Huang

Beilstein J. Org. Chem. 2017, 13, 2094–2114, doi:10.3762/bjoc.13.207

• protective group manipulation and aglycon adjustment often need to be performed on oligosaccharide intermediates, which lower the overall synthetic efficiency. Preactivation-based glycosylation refers to strategies where the glycosyl donor is activated by a promoter in the absence of an acceptor. The

• without the need for any protective group manipulation or aglycon adjustment. Using this method, the 1,4-α-linked tetrasaccharide 37 was prepared in good overall yield. Inspired by Gin’s work, van der Marvel and co-workers developed a sequential glycosylation strategy by combining hemiacetal and

• reactions was attributed to the formation of orthoester and oxazolidine side products due to the basic reaction conditions, which were needed to neutralize the acid formed during glycosylation and to avoid the cleavage of the acid-labile benzylidene protective group. The van der Marel group further applied

Synthesis of benzannelated sultams by intramolecular Pd-catalyzed arylation of tertiary sulfonamides

• Valentin A. Rassadin,
• Mirko Scholz,
• Anastasiia A. Klochkova,
• Armin de Meijere and
• Victor V. Sokolov

Beilstein J. Org. Chem. 2017, 13, 1932–1939, doi:10.3762/bjoc.13.187

• to the N-alkylated precursors of type 5 had to be found. In this context, the 4-methoxybenzyl (PMB) was chosen as a possible protective group for the nitrogen atom, since it can subsequently be removed under acidic [36][37] as well as oxidative conditions [38][39]. In view of the regioselectivety

• can be considered as a viable approach to five- and six-membered benzannelated sultams. The 4-methoxybenzyl group is a suitable protective group for the sultam synthesis since it is stable under the reaction conditions and can be easily removed by acidolysis with trifluoroacetic acid. Structure of

A strategic approach to [6,6]-bicyclic lactones: application towards the CD fragment of DHβE

• Tue Heesgaard Jepsen,
• Emil Glibstrup,
• François Crestey,
• Anders A. Jensen and
• Jesper Langgaard Kristensen

Beilstein J. Org. Chem. 2017, 13, 988–994, doi:10.3762/bjoc.13.98

• Scheme 2). We envisioned that the reductive removal of this protective group would allow for an easier isolation of the volatile final product. Unfortunately, an alkylation of the Cbz-protected propargylamine 10 was unsuccessful. To circumvent this issue an initial protection of the amine 10 using o-NsCl

• hydrogenolysis to form the known tosyl-protected intermediate 7 indicated no signs of product and therefore the CBz strategy was also abandoned. Second strategy without protecting group Since the protective group removal was problematic we decided to preinstall the desired N-substituent and thereby avoid any N

• -protective group (see Scheme 3). The second strategy started with an N-alkylation of the commercially available N-methyl propargylamine with homoallyl bromide providing the tertiary amine 21 in 69% yield which was used without further purification. The subsequent treatment with n-BuLi and trapping with ethyl

Revaluation of biomass-derived furfuryl alcohol derivatives for the synthesis of carbocyclic nucleoside phosphonate analogues

• Bemba Sidi Mohamed,
• Christian Périgaud and
• Christophe Mathé

Beilstein J. Org. Chem. 2017, 13, 251–256, doi:10.3762/bjoc.13.28

• -addition mechanism. The stereochemistry of (+/−)-2 may be ascribed to a nucleophilic attack of the incoming nucleophile from the less-hindered face due to the presence of the silyl protective group. 1H and 13C NMR spectra were in accordance with the presence of a sole diastereoisomer. The reduction of

Silyl-protective groups influencing the reactivity and selectivity in glycosylations

• Mikael Bols and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2017, 13, 93–105, doi:10.3762/bjoc.13.12

• silylene protective groups are also becoming increasingly popular. In carbohydrate chemistry silyl protective groups have frequently been used primarily as an orthogonal protective group to the more commonly used acyl and benzyl protective groups. However, silyl protective groups have significantly

• provide an alternative orthogonal protective group to the more conventional acetyl, benzoyl and benzyl groups. Particularly in oligosaccharide synthesis where many orthogonal hydroxy protective groups are required silicon protective groups have frequently been introduced in both glycosyl donors and

• . Review One of the earliest glycosylations with a persilylated glycosyl donor was carried out by Kihlberg and Broddefalk who needed an acid-labile protective group [5]. They protected a thiocresyl glucoside with TBS groups, oxidized the sulfur to sulfoxide 1 and used the latter to glucosylate the 2-OH of

Modular synthesis of the pyrimidine core of the manzacidins by divergent Tsuji–Trost coupling

• Sebastian Bretzke,
• Stephan Scheeff,
• Felicitas Vollmeyer,
• Friederike Eberhagen,
• Frank Rominger and
• Dirk Menche

Beilstein J. Org. Chem. 2016, 12, 1111–1121, doi:10.3762/bjoc.12.107

• place even without an additional base, which shows the strong influence of the amine protective group on this type of condensation. Importantly, at this stage, the structure of 39 was fully confirmed by X-ray crystallography. As shown in Figure 2, this urea derivative is present as an unsymmetrical

A robust synthesis of 7,8-didemethyl-8-hydroxy-5-deazariboflavin

• Matthias Bender,
• Henrik Mouritsen and
• Jens Christoffers

Beilstein J. Org. Chem. 2016, 12, 912–917, doi:10.3762/bjoc.12.89

• transformed to the corresponding protected ribitylamine via the oxime, which was submitted to reduction with LiAlH4. Key advantage compared to previous syntheses is the utilization of a polyol-protective group which allowed the chromatographic purification of a key-intermediate product providing the target

Stereoselective synthesis of hernandulcin, peroxylippidulcine A, lippidulcines A, B and C and taste evaluation

• Marco G. Rigamonti and
• Francesco G. Gatti

Beilstein J. Org. Chem. 2015, 11, 2117–2124, doi:10.3762/bjoc.11.228

• cleavage of the silyl protective group of 11 with tetra-n-butylammonium fluoride (TBAF) in MeCN and at room temperature, the spectroscopic data of 1 were in complete agreement with those reported in literature [6] ([α]D +130° (c 1.6, CHCl3) vs lit. [31] ([α]D +115° (c 0.64, CHCl3)). The photooxygenation