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

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

• functionalised phenothiazine demonstrated an equipotent MIC value in direct comparison to the parent phenothiazine from which it was derived. The final conjugate was synthesised by amide bond formation between the two components and global deprotection of the PMB protecting groups to unmask the catechol iron

• ). Although the isolated yield of 10 is poor the reaction proceeded with good conversion to the desired product; however, on purification an unknown contaminant was challenging to separate from 9 and we wanted to progress with only analytically pure material for the final deprotection step. We were also

• . In the final PMB global deprotection step we were pleased to observe the formation of our desired final phenothiazine–sideophore conjugate in moderate yield. The addition of anisole to the reaction mixture was found to be essential to inhibit competing electrophilic substitution side reactions. A

Synthesis of functionalised β-keto amides by aminoacylation/domino fragmentation of β-enamino amides

• Pavel Yanev and
• Plamen Angelov

Beilstein J. Org. Chem. 2018, 14, 2602–2606, doi:10.3762/bjoc.14.238

• conditions led to satisfactory yields of keto amides 5 only for substrates 3 with R3 ≠ H (3g–l), while in all other cases (3a–f, R3 = H) gave significant amounts of pyrrolin-4-ones 6 as competing side products (Scheme 2). The relative amount of the side products 6 depended on the deprotection conditions and

• mainly on the duration of the exposure of 3 to acid. Given enough time, the treatment in neat or diluted TFA led to a complete transformation of 3a–f into 6 without formation of the desired β-keto amides 5a–f at all. On the contrary – when the deprotection was carried out for 5 min in neat TFA, the

• pyrrolinones 6 were the minor product and the β-keto amides 5a–f were obtained in higher, although still moderate, yields (Table 1). These results indicated that the acidic conditions required for the Boc deprotection favoured the unwanted side process (Scheme 3) and the aza-Michael/retro-Mannich sequence only

Synthesis of dihydroquinazolines from 2-aminobenzylamine: N³-aryl derivatives with electron-withdrawing groups

• Nadia Gruber,
• Jimena E. Díaz and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2018, 14, 2510–2519, doi:10.3762/bjoc.14.227

• -ABA led to the monosubstitution product using equimolar amounts of both reagents. The individual steps were optimized achieving good to excellent overall yields of the desired heterocycles, avoiding additional protection and deprotection steps. A mechanistic interpretation for the cyclodehydration

• moiety. Our approach involves two selective functionalizations of 2-ABA followed by a ring-closure step. Some selective N-acylations and N-alkylations of this precursor had been described in the literature, involving in many cases additional protection and deprotection steps or affording modest yields

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

• key intermediate 13 removing the p-methoxybenzyl group [24][26][27][28] from 11 failed. Finally, compound 13 was successfully obtained by modifying the sequence of reactions. Deprotection of compound 10 with TFA [24], followed by selective alkylation with benzyl tosylate as previously described

Synergistic approach to polycycles through Suzuki–Miyaura cross coupling and metathesis as key steps

• Sambasivarao Kotha,
• Milind Meshram and
• Chandravathi Chakkapalli

Beilstein J. Org. Chem. 2018, 14, 2468–2481, doi:10.3762/bjoc.14.223

• influence of Zhan-1B catalyst 4 to deliver the cyclized product 131 (91%). Later, TFA-mediated deprotection of cyclized product 131 gave amine 132 (97%). Treatment of chloro derivative 132 with boronate ester 133 provided the SM coupling precursor 134 (77%). Later, an intramolecular SM coupling of Bpin

Synthesis of eunicellane-type bicycles embedding a 1,3-cyclohexadiene moiety

• Alex Frichert,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2018, 14, 2461–2467, doi:10.3762/bjoc.14.222

• coupling to 16 and deprotection to 17 worked satisfyingly. As in the case of a benzene partial structure (8), it was a diol that was formed from 17 under McMurry conditions (20 equiv TiCl4, 40 equiv Zn, THF, rt). No alkene was detected. McMurry-type pinacol cyclizations have shown varying degrees of

• spectrum at 2.61 ppm. This indicates that the alkynyl side chain had been introduced from the same side as the ethoxycarbonyl group. By conversion of the ester to an aldehyde group and deprotection we obtained the subject of study, the putative cyclization precursor 25 (71%). In an orienting reaction