Tuning the stability of alkoxyisopropyl protection groups

• Zehong Liang,
• Henna Koivikko,
• Mikko Oivanen and
• Petri Heinonen

Beilstein J. Org. Chem. 2019, 15, 746–751, doi:10.3762/bjoc.15.70

• , since hydrolysis in water solution is not often a very practical method for detritylation, due to hydrophobicity of the trityl derivative. Nevertheless, half-times for the deprotection of 5’-O-dimethoxytrityl oligonucleotides have been determined under several different conditions [15]. The values

• equilibrium between the protected and deprotected substrates and thus incomplete deprotection [16]. In those cases an acetal protection may offer a more useful solution. We verified also the rapid cleavage of the acetal protections in organic solvents. All the acetals studied were readily removed under the

Synthesis of functionalized diazocines for application as building blocks in photo- and mechanoresponsive materials

• Widukind Moormann,
• Daniel Langbehn and
• Rainer Herges

Beilstein J. Org. Chem. 2019, 15, 727–732, doi:10.3762/bjoc.15.68

• deprotection with TiCl4 the hydroxy-functionalized diazocines 4a and 4b were obtained [32]. The hydroxy groups in 4a and 4b were successfully converted into azides using 2-azido-1,3-dimethylimidazolinium hexafluorophosphate (ADMP) and DBU [33]. The synthesis was completed with a Staudinger reaction to obtain

Efficient synthesis of 4-substituted-ortho-phthalaldehyde analogues: toward the emergence of new building blocks

• Clémence Moitessier,
• Ahmad Rifai,
• Pierre-Edouard Danjou,
• Isabelle Mallard and
• Francine Cazier-Dennin

Beilstein J. Org. Chem. 2019, 15, 721–726, doi:10.3762/bjoc.15.67

• the addition of a protecting step of the unstable key intermediate 4,5-dihydroisobenzofuran-5-ol. Oxidation and deprotection steps were also studied in order to provide an effective availability of these two dialdehyde compounds that may increase their future applications. Keywords: demethylation

• -substituted OPA synthesis represents a major limiting factor to their potential applications. Herein, we set forth a new protection-deprotection strategy which leads to 4-MeO-OPA and 4-HO-OPA as reliable structures for organic and analytical chemistries. A variety of protecting groups of key 4,5

• -dihydroisobenzofuran-5-ol intermediate has been tested and oxidation parameters of the dedicated structures were optimized. Finally, a rapid deprotection step was initiated to afford 4-MeO-OPA and 4-HO-OPA with 51% overall yield. Results and Discussion Firstly, 2-((prop-2-ynyloxy)methyl)furan (2) was synthesized

Homo- and hetero-difunctionalized β-cyclodextrins: Short direct synthesis in gram scale and analysis of regiochemistry

• Gábor Benkovics,
• Mihály Bálint,
• Éva Fenyvesi,
• Erzsébet Varga,
• Szabolcs Béni,
• Konstantina Yannakopoulou and
• Milo Malanga

Beilstein J. Org. Chem. 2019, 15, 710–720, doi:10.3762/bjoc.15.66

• isolation of the capped β-CD derivative or the substitution products obtained by cap displacement which generally leads to low yields of the isolated pure compounds. Alternatively, the preparation of homo-difunctionalized CDs is based on selective deprotection of persilylated or peralkylated CDs. This

• approach, developed by Sinay et al. [15] and studied in depth on perbenzylated CDs, was extended up to hexa-heterodifferentiation of α-CD by Sollogoub and co-workers [16]. The regioselective DIBAL deprotection has also been applied on the primary side of 6-persilylated-2,3-permethylated or 6-persilylated

• -2,3-perbenzylated CDs by Ling et al. [17] and on the secondary side of permethylated CDs by Sollogoub and Zhang et al. [18]. The selective deprotection strategy is advantageous in terms of applicability and product yields, however, compared to the direct difunctionalization approach, it requires two

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• into a 1-nonafluorobutanesulfonate group is presented, that – like the closely related triflate group – allows transition metal-catalyzed coupling reactions or nucleophilic substitutions [52]. The selected three examples presented in Scheme 13 show striking differences in the deprotection step [33

• compound PM53. This method is certainly not applicable to pyrimidines with alkenyl substituents, but in this case 2-(trimethylsilyl)ethoxy-substituted compounds such as PM29 can be used, whose deprotection with trifluoroacetic acid proceeds at room temperature. The obtained 5-hydroxy-pyrimidines can be

• PM50; (NMO = N-methylmorpholine N-oxide). Deprotection of 5-alkoxy-substituted pyrimidines PM2, PM20 and PM29 and conversion into nonaflates PM52 and PM54; (Nf =1-nonafluorobutanesulfonyl). Palladium-catalyzed coupling reactions of PM54 and PM12 giving rise to new pyrimidine derivatives PM55–58

Design and synthesis of multivalent α-1,2-trimannose-linked bioerodible microparticles for applications in immune response studies of Leishmania major infection

• Chelsea L. Rintelmann,
• Tara Grinnage-Pulley,
• Kathleen Ross,
• Daniel E. K. Kabotso,
• Angela Toepp,
• Anne Cowell,
• Christine Petersen,
• Balaji Narasimhan and
• Nicola Pohl

Beilstein J. Org. Chem. 2019, 15, 623–632, doi:10.3762/bjoc.15.58

• used alkene fluorous tag [11][52][53]. The CbzF tag was also removed during global deprotection to readily provide an amine handle for conjugation to the dendrimeric core, avoiding further synthetic manipulations. Synthesis of glycodendrimer Attachment of the 5(6)-TAMRA fluorophore to the dendrimeric

• dendrimer. Therefore, we settled on first coupling Nα-Fmoc-Nε-(4-methyltrityl)-L-lysine (17) to the dendrimeric amine 18 by standard HATU amide coupling conditions (Scheme 3). The protecting groups were chosen specifically for selective deprotection and compatibility with the TAMRA fluorophore, which is

• was selectively hydrolyzed with CH2Cl2/TFE/AcOH 3:1:1 and trapped by triethylsilane, providing free amine 23 [54]. At this point, the epsilon amine 23 was coupled with TAMRA-NHS, followed by acidic deprotection of the tert-butyl esters to afford the triacid 25. Then, the successful coupling of the

Synthesis of the aglycon of scorzodihydrostilbenes B and D

• Katja Weimann and
• Manfred Braun

Beilstein J. Org. Chem. 2019, 15, 610–616, doi:10.3762/bjoc.15.56

• - and 3,4-dimethoxystyrene in a completely regioselective manner. Thus, oxygenated dihydrostilbenes are obtained that feature the skeleton of scorzodihydrostilbenes – antioxidative agents that were recently isolated from Scorzonera radiata. Selective deprotection liberates the corresponding phenols

• acetate was found to be the appropriate solvent, whereas the starting materials did not dissolve in methanol or ethanol. The reaction required a hydrogen overpressure of 3 bar for one to three days at room temperature, but even then, the deprotection was not completed in all cases. On the other hand

Selectivity in multiple multicomponent reactions: types and synthetic applications

• Ouldouz Ghashghaei,
• Francesca Seghetti and
• Rodolfo Lavilla

Beilstein J. Org. Chem. 2019, 15, 521–534, doi:10.3762/bjoc.15.46

• , symmetrical adducts or polymers; ii) structurally preorganized systems allowing the generation of macrocycles and iii) selective processes in which a determined combination arises in a sequential manner, either directly or indirectly, through functional group deprotection/generation. Stereoselectivity (where

• temporarily blocking one of the reactive sites along the process. This sequential approach involves protection/deprotection steps in which one of the building blocks contains a protected FG to be subsequently (and selectively) activated for the following MCRs. For instance, the examples shown in Scheme 13

• illustrate a repetitive Ugi 4CR-deprotection-Ugi 4CR protocol to obtain peptide nucleic acid (PNA) oligomers (Scheme 13A) [49], peptidic tetrazoles and hydantoinimides (Scheme 13B) [50], respectively. Incidentally, the later processes take place in solid phase, which enhances their synthetic suitability. The

Convergent synthesis of the pentasaccharide repeating unit of the biofilms produced by Klebsiella pneumoniae

• Arin Gucchait,
• Angana Ghosh and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2019, 15, 431–436, doi:10.3762/bjoc.15.37

• reaction conditions furnished the D-glucuronic acid containing pentasaccharide derivative, which on global deprotection under hydrogenolysis in the presence of Pearlman’s catalyst [40] afforded the target pentasaccharide as its 2-aminoethyl glycoside 1 in 61% yield (Scheme 4). Conclusion In summary, a

Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

• or gas HCl in methanol or ethanol) and (30% aqueous ammonia in methanol at −10 °C) basic conditions. It was demonstrated that the best results in terms of β-NR+Cl− purity and yields were achieved when the acetate deprotection was carried under anhydrous conditions using 3 molar equivalents of 1.25 M

• HCl in methanol. A significant advantage of an acidic methanolic deprotection is the formation of methyl acetate rather than acetamide. The later byproduct has been classified by the International Agency for Research on Cancer (IARC) as a Group 2B compound, i.e., as a possible human carcinogen, and

• 61% yield using acetonitrile at −5 °C. Unfortunately, the methods for the deprotection of 8b were not described. Mikhailopulo et al. [26] studied a range of solvents, such as sulfolane, sulfur dioxide and nitromethane, to improve on the glycosylation reaction outcomes. It was found that yields and

Thiol-free chemoenzymatic synthesis of β-ketosulfides

• Adrián A. Heredia,
• Martín G. López-Vidal,
• Marcela Kurina-Sanz,
• Fabricio R. Bisogno and
• Alicia B. Peñéñory

Beilstein J. Org. Chem. 2019, 15, 378–387, doi:10.3762/bjoc.15.34

• the enol ester. Hence, only acetate was easily accepted while ethyl thiocarbonate 1n (Table 2, entry 14) and benzoate enol esters 1o (Table 2, entry 15), were recovered unaltered. These results pave the way for developments of orthogonal deprotection protocols in the future. Once the enzymatic

Synthesis of C₃-symmetric star-shaped molecules containing α-amino acids and dipeptides via Negishi coupling as a key step

• Sambasivarao Kotha and
• Saidulu Todeti

Beilstein J. Org. Chem. 2019, 15, 371–377, doi:10.3762/bjoc.15.33

• acids were incorporated in the star-shaped molecule. In this regard, the Negishi cross-coupling product 10 was treated with TFA in CH2Cl2 at room temperature for 1 h to give the Boc-deprotection product, which was directly treated with Boc-Val-OH or Boc-Phe-OH in the presence of HBTU and DIPEA in CH2Cl2

• at room temperature for 5 h to give trimeric derivatives 12 (73%) and 13 (81%), respectively. Further, trimer 12 was subjected to another Boc-deprotection to give the tris-amine 14 in 95% yield (Scheme 4). Conclusion We have demonstrated a simple synthetic strategy toward star-shaped molecules

• the reaction mixture was stirred at room temperature for 1 h. Then, the mixture was concentrated at reduced pressure to remove the solvent and dried under vacuum. Later, without further purification the Negishi coupling deprotection product was reacted with 3 equiv of thiophene 2-carboxylic acid or

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

• give dimethyl ester 98 (Scheme 25). Silver oxide-promoted methylation introduces a MeO-C4 unit. Regioselective aziridine ring opening in 99 was then carried out in the known way with benzyl alcohol or methanol to produce substituted dimethyl L-glutamates 100 and 101. To ensure clean deprotection in the

• (3R,4R,5R)-112 which were separated as isopropylidene derivatives (3R,4R,5S)-113 and (3R,4R,5R)-113. After deprotection they were converted into (2R,3R,4R)-4 and (2S,3R,4R)-4, respectively, although the final hydrolytic step in the synthesis of (2S,3R,4R)-4 had to be carried out carefully since its

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

• intermediates by simple fluorous solid-phase extraction (F-SPE). Interestingly, the fluorous tag would be introduced by acylation using commercially available heptadecafluoroundecanoyl chloride and its deprotection would not involve any additional step at the end of the synthesis. N-Trifluoroacetyl (N-TFA

• assays, deprotection of dimer 6 and tetramer 14β were accomplished (Scheme 5). Compound 14α was also submitted to the deprotection sequence to obtain a non-natural α-containing oligosaccharide. Basic hydrolysis using H2O2/LiOH and then NaOH followed by selective N-acetylation in MeOH afforded CS

Ruthenium-based olefin metathesis catalysts with monodentate unsymmetrical NHC ligands

• Veronica Paradiso,
• Chiara Costabile and
• Fabia Grisi

Beilstein J. Org. Chem. 2018, 14, 3122–3149, doi:10.3762/bjoc.14.292

• from its precursor 108 by deprotection under acidic conditions. The cis isomers 113–115 exhibited catalytic activity only at high temperatures, where they likely reassume the trans form which is characteristic for the Grubbs-type ruthenium carbene complexes. In order to develop a new structural class

A simple and effective preparation of quercetin pentamethyl ether from quercetin

• Jin Tatsuzaki,
• Tomohiko Ohwada,
• Yuko Otani,
• Reiko Inagi and
• Tsutomu Ishikawa

Beilstein J. Org. Chem. 2018, 14, 3112–3121, doi:10.3762/bjoc.14.291

• resulting 3,7,4'-tribenzylquercetin, and deprotection of the benzyl groups. These results allowed us to deduce the reactivity order of the five OH functions on 2 to be 7 ≈ 4' > 3 > 3' > 5, and the rationale was accessed by computational studies. Conformation of quercetin and stability of its oxyanions

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

• part in Supporting Information File 1). However, in the synthesis of ON1 and ON2 the yield dropped to approximately 40% after the incorporation of the modified unit. The analysis of the crude product by LC–MS after cleavage from the solid support and deprotection, revealed the presence of 5

Cross metathesis-mediated synthesis of hydroxamic acid derivatives

• Shital Kumar Chattopadhyay,
• Subhankar Ghosh and
• Suman Sil

Beilstein J. Org. Chem. 2018, 14, 3070–3075, doi:10.3762/bjoc.14.285

• -isopropoxyphenylmethylene)ruthenium] (HG-II) was used under identical conditions. Hydrogenation of the later in the presence of Pd(OH)2/C proceeded uneventfully resulting in the saturation of the double bond as well as concommitant deprotection of the O-benzyl group. The one-pot CM-hydrogenation sequence using the same

Ring-closing-metathesis-based synthesis of annellated coumarins from 8-allylcoumarins

• Christiane Schultze and
• Bernd Schmidt

Beilstein J. Org. Chem. 2018, 14, 2991–2998, doi:10.3762/bjoc.14.278

• -protected precursors 5a–d using the conditions of the microwave-promoted tandem sequence [29]. The intermediate MOM-protected coumarins were not isolated but immediately deprotected by treatment with aq HCl in methanol. Isolation of the MOM-protected coumarins 7 [29] and deprotection in a separate step

Stereodivergent approach in the protected glycal synthesis of L-vancosamine, L-saccharosamine, L-daunosamine and L-ristosamine involving a ring-closing metathesis step

• Pierre-Antoine Nocquet,
• Aurélie Macé,
• Frédéric Legros,
• Jacques Lebreton,
• Gilles Dujardin,
• Sylvain Collet,
• Arnaud Martel,
• Bertrand Carboni and
• François Carreaux

Beilstein J. Org. Chem. 2018, 14, 2949–2955, doi:10.3762/bjoc.14.274

• Hoveyda–Grubbs second-generation (HG-II) catalyst to deliver the corresponding dihydropyrans 16 in excellent yields given that this kind of reaction can be sensitive to the substitution pattern contained in the substrate [11]. After silyl deprotection, the key C–H amination precursors 17a,b for the

Synthesis of unnatural α-amino esters using ethyl nitroacetate and condensation or cycloaddition reactions

• Glwadys Gagnot,
• Vincent Hervin,
• Eloi P. Coutant,
• Sarah Desmons,
• Racha Baatallah,
• Victor Monnot and
• Yves L. Janin

Beilstein J. Org. Chem. 2018, 14, 2846–2852, doi:10.3762/bjoc.14.263

• to the toluene solution containing compound 40. This afforded, after overnight stirring, the isomerized compound 41 in a 69% yield. Finally, the deprotection of the amine function was achieved with the use of an excess of hydrogen chloride in 1,4-dioxane to give the target α-amino ester 43

Enhanced single-isomer separation and pseudoenantiomer resolution of new primary rim heterobifunctionalized α-cyclodextrin derivatives

• Iveta Tichá,
• Gábor Benkovics,
• Milo Malanga and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2018, 14, 2829–2837, doi:10.3762/bjoc.14.261

• practically no regioselectivity was observed. On the other hand, the dibromo-α-CD derivative was also prepared using a four-step indirect method involving DIBAL-H deprotection (reaction 4, Scheme 2) [10][30]. This method generated the AD regioisomer exclusively without AB or AC regioisomers as byproducts

• the determination of the regioisomeric pattern was gathered in reactions 1 and 4. Reaction 1 yielded mostly AB regioisomer 4b, whereas reaction 4 exclusively generated pure AD regioisomer 4d. These compounds, previously prepared by disulfonyl capping [17] (reaction 1) and DIBAL-H deprotection [10

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

• conditions, followed by amide formation with ortho-chlorobenzoic acid and a final acidic deprotection step to provide the desired analogue 4. Despite the change of the initial strategy and resulting elongation of the synthetic route, the overall synthesis still proved to be very efficient, delivering 4 in 6

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

• acceptors were obtained via Zemplén deprotection in 94% and 90% yield for the 6-O-TBDPS 9 and 6-O-Bn 10, respectively (Scheme 2). The acceptors could in turn be transformed into the corresponding donors in three simple steps by first benzylating the 3,4-diol (11 and 12), hydrolyzing the thiophenol using NBS

• terminal part of the LTA from S. pneumoniae. The deprotection of disaccharide 22 to give 27 followed by formation of the trichloroacetimidate 28 proceeded smoothly, as shown in Scheme 6. The following glycosylation using MeCN as solvent relied on the nitrile effect to afford the desired β-anomer 29 in 74

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

• ineffective, ii) possess low resin loading, iii) incompatible in medium to strongly acidic [30] or basic conditions employed for deprotection of coupled amino acids and iv) undergo premature cleavage of polypeptide chain from solid support resulting in moderate yield during deprotection of acid sensitive side

• (4-methyltrityl) > Mmt (4-methoxytrityl). In our initial attempt, we opined that the Mtt- (4-methyltrityl-) protected ε-amino group of Fmoc-Lys-(Mtt)-OH should undergo selective cleavage under mildly acidic conditions without cleavage of polypeptide chain 9a from the resin. Selective deprotection of

• synthetic strategy. Usually, the allyl protecting group in N-Fmoc-Lys(Alloc)-OH is deprotected using Pd(PPh3)4 catalyst. However, the sulfur atom present in the cysteine moiety of the chelating core is known to poison palladium catalysts resulting in complete failure of the deprotection of the ε-amino allyl