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

• , 28.0; HRMS (ESI) m/z: [M + Na]+ calcd for C30H46N2O9, 601.3096; found, 601.3092. Procedure for debenzylation of benzyl tris(tert-butoxy)-protected DUPA precursor 3 to give (S)-5-(tert-butoxy)-4-(3-((S)-1,5-di-tert-butoxy-1,5-dioxopentan-2-yl)ureido)-5-oxopentanoic acid (4): To a solution of benzyl tris

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

• achieved by N-debenzylation under catalytic hydrogenolysis conditions followed by protection of the liberated amines with CbzCl furnishing fully protected pyrrolidines 14 [35] and 15. Exposure of 14 to a catalytic amount of PTSA (0.04 equiv) in a mixture of CH2Cl2/MeOH 30:1 (v/v) resulted in rapid cleavage

Aminomethylation/hydrogenolysis as an alternative to direct methylation of metalated isoquinolines – a novel total synthesis of the alkaloid 7-hydroxy-6-methoxy-1-methylisoquinoline

• Benedikt C. Melzer,
• Jan G. Felber and
• Franz Bracher

Beilstein J. Org. Chem. 2018, 14, 130–134, doi:10.3762/bjoc.14.8

• material 3. Due to the very similar polarities of 3 and 4, chromatographic separation was very tedious, and only 34% of methyl compound 4 was isolated, accompanied by about 30% of starting material 3 and mixed fractions. Debenzylation of 4 by catalytic hydrogenation in methanol solution under palladium

• hydrogenolysis experiments with 5, which were aimed at simultaneous O-debenzylation at the 7-position and conversion of the N,N-dimethylaminomethyl group at C1 into a methyl group. Hydrogenation in presence of palladium as catalyst at 1 bar in the presence or absence of small amounts of sulfuric acid gave the

• highly reactive benzylammonium residue still takes place, but O-debenzylation is predominantly suppressed by this catalyst poison. Finally, poisoning of the catalyst was prevented by simply passing a solution of the methoiodide 7 through a chloride-loaded ion exchanger prior to catalytic hydrogenation

Intramolecular glycosylation

• Xiao G. Jia and
• Alexei V. Demchenko

Beilstein J. Org. Chem. 2017, 13, 2028–2048, doi:10.3762/bjoc.13.201

• debenzylation followed by global acetylation to afford product 30. The extension of this approach to convergent oligosaccharide synthesis and reiterative sequencing in presented in Scheme 8. Thus, maltose and lactose disaccharide building blocks were linked via the xylylene tether, and the resulting compound 31

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• , multi-step intermediates and the final debenzylation is achieved by using the highly inconvenient Birch reduction. 4 Direct activation of the anomeric center Over the past 20 years, primarily the Shoda, Fairbanks, and Nitz groups have performed extensive studies on molecules that selectively react at

Synthesis of ribavirin 2’-Me-C-nucleoside analogues

• Fanny Cosson,
• Aline Faroux,
• Jean-Pierre Baltaze,
• Jonathan Farjon,
• Régis Guillot,
• Jacques Uziel and
• Nadège Lubin-Germain

Beilstein J. Org. Chem. 2017, 13, 755–761, doi:10.3762/bjoc.13.74

• (triazole), 128.6, 128.2, 127.7 (Ph), 100.8 (d, J = 190 Hz, C2), 82.2 (C4), 79.7 (d, J = 39 Hz, C1), 73.9 (d, J = 23 Hz, C3), 61.3 (C5), 53.0 (-CH2Ph), 17.2 (d, J = 26 Hz, CH3); 19F NMR (376.2 MHz, MeOD) −158.2 (m); HRMS calcd for C16H20FN4O4, 351.1469; found, 351.1468. Debenzylation proceeded in ethanol (5

Derivatives of the triaminoguanidinium ion, 5. Acylation of triaminoguanidines leading to symmetrical tris(acylamino)guanidines and mesoionic 1,2,4-triazolium-3-aminides

• Jan Szabo,
• Julian Greiner and
• Gerhard Maas

Beilstein J. Org. Chem. 2017, 13, 579–588, doi:10.3762/bjoc.13.57

• -1,2,4-triazolium salts by protonation or methylation at the anionic hydrazinide nitrogen atom and into highly substituted and functionalized 1,2,4-triazoles by N-debenzylation through catalytic hydrogenation. Thus, the reaction of triaminoguanidine and its 1,2,3-tribenzyl derivative with acid chlorides

• )guanidinium salts 4 and 5 with acyl chlorides to give 1,2,3-tris(acylamino)guanidines 6 and mesoionic 1,2,4-triazolium-3-aminides 7. See Table 1 for Ar, R and yields of 7. Protonation and methylation of 1,2,4-triazolium-3-aminides 7b,c. Catalytic hydrogenation/debenzylation of betaines 7. 1,2,4-Triazolium-3

Studies directed toward the exploitation of vicinal diols in the synthesis of (+)-nebivolol intermediates

• Runjun Devi and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2017, 13, 571–578, doi:10.3762/bjoc.13.56

• subjected to a Sharpless asymmetric dihydroxylation with AD-mix-α in t-BuOH/H2O (1:1) at 0 °C for 24 h furnishing syn-2,3-dihydroxy ester 19 in a high yield of 92%. For the synthesis of syn-2,3-dihydroxy ester 20, AD-mix-β was employed. Debenzylation of diol 20 with Pd–C and H2 at room temperature produced

• reaction [34] to obtain the β-hydroxy-α-tosyloxy esters 24 and 25, respectively (Scheme 6). Panda and co-worker applied a three-step reaction sequence involving epoxidation/debenzylation/epoxide ring-opening to convert the β-hydroxy-α-tosyloxy ester into the corresponding 2-substituted chroman derivative

• . However, it has been reviewed that not only benzylic epoxides but also non-benzylic epoxides are sensitive to the standard hydrogenation/debenzylation conditions [35]. Whereas benzylic epoxides are highly sensitive to hydrogenation conditions, non-benzylic epoxides, depending on the reaction conditions

Brønsted acid-mediated cyclization–dehydrosulfonylation/reduction sequences: An easy access to pyrazinoisoquinolines and pyridopyrazines

• Ramana Sreenivasa Rao and
• Chinnasamy Ramaraj Ramanathan

Beilstein J. Org. Chem. 2017, 13, 428–440, doi:10.3762/bjoc.13.46

• the reduction sequence at room temperature (Scheme 7). The synthesis of praziquantel from intermediate 11h was accomplished through N-debenzylation at 80 °C under 1 atmosphere of H2 in the presence of Pd/C [40]. The present synthetic protocol involves the debenzylation reaction under milder conditions

The reductive decyanation reaction: an overview and recent developments

• Jean-Marc R. Mattalia

Beilstein J. Org. Chem. 2017, 13, 267–284, doi:10.3762/bjoc.13.30

• , Scheme 26) [125]. The first observation was that surprisingly, the reaction of 2,2-dibenzylmalononitrile (72b) provided both debenzylated (2-benzylmalononitrile, 19%) and decyanation (73b, 75%) products. In contrast, the corresponding dibenzylcyanoacetate led exclusively to the debenzylation product [126

Iodination of carbohydrate-derived 1,2-oxazines to enantiopure 5-iodo-3,6-dihydro-2H-1,2-oxazines and subsequent palladium-catalyzed cross-coupling reactions

• Michal Medvecký,
• Igor Linder,
• Luise Schefzig,
• Hans-Ulrich Reissig and
• Reinhold Zimmer

Beilstein J. Org. Chem. 2016, 12, 2898–2905, doi:10.3762/bjoc.12.289

• hydrogenolysis processes. As already discussed in previous publications [23][53], the hydrogenolysis of 1,2-oxazines of type 3 with palladium on charcoal very likely starts with a fast N-debenzylation, followed by the reduction of the C-4/C-5 double bond forming the corresponding 3,4,5,6-tetrahydro-2H-1,2

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• separated by column chromatography. After debenzylation, the resultant primary amines were connected with amido aldehydes 6 substituted with different moieties R and R' by reductive amination with R being either a hydroxy group or a hydrogen and R' representing an alkyl, allyl, ester or a protected amino

Synthesis and in vitro cytotoxicity of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine

• Štěpán Horník,
• Lucie Červenková Šťastná,
• Petra Cuřínová,
• Jan Sýkora,
• Kateřina Káňová,
• Roman Hrstka,
• Ivana Císařová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2016, 12, 750–759, doi:10.3762/bjoc.12.75

• :2,3-dianhydro-4-O-benzyl-β-D-mannopyranose (10, one of the Černý epoxides available from D-glucal [31][32][33] or levoglucosan [34]). Regioselective azidolysis [21][35][36] of 10 yielded 2-azido alcohol 11 which was converted to 12 by benzoylation at O-3 and debenzylation at O-4. To prevent azide

• reduction, oxidative debenzylation [24] was applied instead of the more common hydrogenation. Debenzylation of 10 gave dianhydro derivative 13 [34][37] (available also directly from D-glucal [31][33] or from levoglucosan [38]) which was converted to 14 by Latrell–Dax inversion at C-4 [39]. O-Benzylation [40

• 75 °C (conditions used for fluorination of 11), or in dichloromethane at rt was attempted. Disappointingly, only unreacted 15 was recovered. A very slow formation of several unidentified fluorine-containing compounds (19F NMR) was observed on prolonged reaction times. Oxidative debenzylation of 19

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• tertiary amide was then formed by sequential reaction of carboxylic acid 53 with oxalyl chloride and N-methylaniline derivative 54. The following two-step debenzylation sequence afforded alcohol 55 which was converted to the corresponding mesylate, serving as a key intermediate for the construction of the

Synthesis, antimicrobial and cytotoxicity evaluation of new cholesterol congeners

• Mohamed Ramadan El Sayed Aly,
• Hosam Ali Saad and
• Shams Hashim Abdel-Hafez

Beilstein J. Org. Chem. 2015, 11, 1922–1932, doi:10.3762/bjoc.11.208

• be removed under these conditions. For comparison reasons, derivative 31, that has the cholesterol moiety at the C-4 carbon of the B ring of the lactose moiety, was prepared by CuAAC of substrate 30 with 3 to afford intermediate 31 in 74% yield. This intermediate resisted reductive debenzylation

• under the same conditions and compound 32 also could not be obtained [44][45]. To investigate, whether the triazole or the cholesterol entities are not compatible with these debenzylation conditions, probes 36 and 38 (Scheme 7) were prepared by CuAAC of derivative 34 with compounds 35 and 9b

• constant due to a weak equatorial–diaxial coupling. Compounds 36 and 38 were subjected to reductive debenzylation. While, compound 38 could be debenzylated in excellent yield, quinoline derivative 36 could not be debenzylated even in the presence of Pd(OH)2. Consequently, it might be concluded that bulky

Fe(II)/Et₃N-Relay-catalyzed domino reaction of isoxazoles with imidazolium salts in the synthesis of methyl 4-imidazolylpyrrole-2-carboxylates, its ylide and betaine derivatives

• Ekaterina E. Galenko,
• Olesya A. Tomashenko,
• Alexander F. Khlebnikov,
• Mikhail S. Novikov and
• Taras L. Panikorovskii

Beilstein J. Org. Chem. 2015, 11, 1732–1740, doi:10.3762/bjoc.11.189

• for debenzylation of 1-benzyl-3-pyrrol-3-yl-1H-imidazol-3-ium bromides 1j,k,n. 1-Benzyl-1H-imidazol-3-ium bromide 1 (100 mg) was dissolved in MeOH (10 mL), Pd/C (10 mg, 10 wt %) and ammonium formate (10 equiv) were added. The suspension was stirred under reflux for 1 h (monitored by TLC). The reaction

Selective methylation of kaempferol via benzylation and deacetylation of kaempferol acetates

• Qinggang Mei,
• Chun Wang,
• Weicheng Yuan and
• Guolin Zhang

Beilstein J. Org. Chem. 2015, 11, 288–293, doi:10.3762/bjoc.11.33

• of dimethyl sulfate at room temperature provided 10 with a yield of 85%. The final deprotection of 10 involving deacetylation with 7.0 M methanolic ammonia and debenzylation by hydrogenolysis with 10% palladium on carbon in EtOAc/MeOH (1:3) at room temperature afforded 12 (Scheme 2). In order to

Enantioselective synthesis of polyhydroxyindolizidinone and quinolizidinone derivatives from a common precursor

• Nemai Saha and
• Shital K. Chattopadhyay

Beilstein J. Org. Chem. 2014, 10, 3104–3110, doi:10.3762/bjoc.10.327

• latter to a hydroxymethyl unit, and subsequent debenzylation of the resulting 22 led to the desired tetrahydroxyquinolizidine derivative 23 in an overall yield of 45% over six steps. Similarly, the pentahydroxylated quinolizidine derivative 24 was prepared from the triol 21 in view of the importance of

The Shono-type electroorganic oxidation of unfunctionalised amides. Carbon–carbon bond formation via electrogenerated N-acyliminium ions

• Alan M. Jones and
• Craig E. Banks

Beilstein J. Org. Chem. 2014, 10, 3056–3072, doi:10.3762/bjoc.10.323

• (Fmol−1) was required [20]. The authors also detail a deallylation and a debenzylation deprotection method to 108. An alternative strategy to chiral amino acids was demonstrated by Kuźnik and colleagues [98] through the electrochemical preparation of 3-triphenylphosphine-2,5-piperazinediones as chiral

Synthesis of modified cyclic and acyclic dextrins and comparison of their complexation ability

• Kata Tuza,
• László Jicsinszky,
• Tamás Sohajda,
• István Puskás and
• Éva Fenyvesi

Beilstein J. Org. Chem. 2014, 10, 2836–2843, doi:10.3762/bjoc.10.301

• synthetic route was worked out via bromination, benzylation, deacetylation and debenzylation to obtain the 2-hydroxypropyl maltooligomer counterparts. The complexation properties of non-modified and modified cyclic and acyclic dextrins were studied and compared by photon correlation spectroscopy (PCS) and

• chloroform/acetone for bromination, 85:15 v/v alcohol free chloroform:acetone for benzylation and 10:7 v/v dioxane:satd. aq ammonia for hydroxypropylation and debenzylation; visualization: 15% cc. H2SO4 in 96% EtOH. Synthesis of HP-maltooligomers 1-Bromo-peracetyl-maltooligomers, according to [14

Synthesis of phosphoramidites of isoGNA, an isomer of glycerol nucleic acid

• Keunsoo Kim,
• Venkateshwarlu Punna,
• Phaneendrasai Karri and
• Ramanarayanan Krishnamurthy

Beilstein J. Org. Chem. 2014, 10, 2131–2138, doi:10.3762/bjoc.10.220

• proved problematic and no product was detected. Therefore, in the adenine case, we tried a direct SN2 reaction of N6-benzoyladenine with tosyl derivative 6, which was only moderately successful (30% yield of 7). Unexpectedly, in both the thymine and adenine cases, the subsequent debenzylation reaction

Synthesis of rigid p-terphenyl-linked carbohydrate mimetics

• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 1749–1758, doi:10.3762/bjoc.10.182

• debromination. The debenzylation and the N–O bond cleavage occur as next steps. Under these improved conditions the isomeric bicyclic 1,2-oxazine 15b was converted into aminopyran 17b in a good yield of 77%. The formed aminopyrans 17a and 17b can be regarded as amino C-glycosides. Compound 17a is related to

Expedient synthesis of 1,6-anhydro-α-D-galactofuranose, a useful intermediate for glycobiological tools

• Luciana Baldoni and
• Carla Marino

Beilstein J. Org. Chem. 2014, 10, 1651–1656, doi:10.3762/bjoc.10.172

• from galactose (Scheme 1) [16]. The 1,6-ring closure was produced by the O-debenzylation of the 6-hydroxy group of 4 and the nucleophilic attack of this hydroxy group to C-1, promoted by SnCl4. An optimized synthesis of 2 following this strategy has recently been described with an overall yield of 48

Amino acid motifs in natural products: synthesis of O-acylated derivatives of (2S,3S)-3-hydroxyleucine

• Oliver Ries,
• Martin Büschleb,
• Markus Granitzka,
• Dietmar Stalke and
• Christian Ducho

Beilstein J. Org. Chem. 2014, 10, 1135–1142, doi:10.3762/bjoc.10.113

• sequence. Finally, the previously reported hydrogenolytic debenzylation of 4 [32] provided amino alcohol key intermediate 5 in quantitative yield for the deprotection step and in 29% overall yield over 7 steps from D-serine (2, Scheme 1). It should be noted that Garner's aldehyde is often used instead of

Towards stereochemical control: A short formal enantioselective total synthesis of pumiliotoxins 251D and 237A

• Jie Zhang,
• Hong-Kui Zhang and
• Pei-Qiang Huang

Beilstein J. Org. Chem. 2013, 9, 2358–2366, doi:10.3762/bjoc.9.271

• steps), from which only the major product 16 was isolated (Scheme 6). For the chemoselective debenzylation, lithium naphthalenide (LN) was used [48]. To our disappointment, attempted cleavage of the benzyl group by LN (THF, −40 °C to rt, 2 h) gave the desired 18 in only 20% yield along with 60% of the

• recovered starting material 16. Due to the low yield in the debenzylation process, we decided to change the O-protecting group from benzyl to TBDMS, namely, use of TBDMS ether 14 as the starting material. Thus, (R)-3-(tert-butyldimethylsilyloxy)glutarimide 14 [49] was prepared from the known (R)-3