Selectivity in multiple multicomponent reactions: types and synthetic applications

Ouldouz Ghashghaei,
Francesca Seghetti and
Rodolfo Lavilla

Review
Published 21 Feb 2019

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1. Graphical Abstract
2. Scheme 1: Selectivity levels found in multiple multicomponent reactions. I) Innate selectivity; II) sequentia...
  
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3. Scheme 2: Indiscriminate double Ugi MCR upon pyridine-2,6-dicarboxylic acid.
  
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4. Scheme 3: Representative examples of MCR-polymer synthesis. A) Biginelli HTS of polymers; B) Passerini;- C) U...
  
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5. Scheme 4: Concept of multicomponent macrocyclization.
  
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6. Scheme 5: Supramolecular structures out of MMCR macrocyclizations.
  
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7. Scheme 6: Macrocyclization by MMCRs. A) Staudinger MCR; B) boronic-imine MCR.
  
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8. Scheme 7: Selective Sequential MMCRs. A and B) MCRs involving terephthalaldehyde; C) Multiple GBB processes w...
  
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9. Scheme 8: Biased substrates for selective MMCRs.
  
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10. Scheme 9: The Union concept. A) Asinger–Ugi combination; B) Passerini–Ugi/azide from anthranilic acid; C) Pas...
  
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11. Scheme 10: Relevant examples of consecutive MCRs exploiting the Union Concept. A) Petasis-Ugi combination; B) ...
  
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12. Scheme 11: Selective MMCRs featuring FGs with distinct reactivity along the sequence. A) Synthesis of aminomet...
  
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13. Scheme 12: High order MMCRs. A) Ugi/Ugi–Smiles 7C combination; B) imidazoline-N-cyanomethylamide-Ugi union lea...
  
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14. Scheme 13: Consecutive Ugi 4CR-deprotection–Ugi 4CR strategy towards A) PNA oligomers and B) peptidic tetrazol...
  
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15. Scheme 14: Sequential Ugi 4CR-deprotection access to cyclopeptoids.
  
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16. Scheme 15: Stepwise access to 6-aminopenicillanic acid derivative through an Asinger, deprotection, Joullié ap...
  
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17. Scheme 16: A triple MCR-deprotection approach affording anticancer peptidomimetics.
  
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Beilstein J. Org. Chem. 2019, 15, 521–534, doi:10.3762/bjoc.15.46

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Design of indole- and MCR-based macrocycles as p53-MDM2 antagonists

Constantinos G. Neochoritis,
Maryam Kazemi Miraki,
Eman M. M. Abdelraheem,
Ewa Surmiak,
Tryfon Zarganes-Tzitzikas,
Beata Łabuzek,
Tad A. Holak and
Alexander Dömling

Full Research Paper
Published 20 Feb 2019

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1. Graphical Abstract
2. Scheme 1: MCR approach to indole-based macrocycles; a more effective strategy is proposed in this work, based...
  
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3. Scheme 2: Reaction of unprotected diamines 3 with cyclic anhydrides 4 at rt affording α,ω-amino acids 5 in qu...
  
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4. Scheme 3: Ugi macrocyclization in a one-pot fashion and synthesis of diverse indole-based macrocycles. The ci...
  
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5. Figure 1: (A) Modeling of the macrocycle 2h (cyan sticks) and 2n (magenta sticks) into the MDM2 receptor (PDB...
  
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6. Figure 2: (A) Overlay of ¹ H,¹⁵N-HSQC spectra of the reference MDM2 (red) and the titration steps with the 2i...
  
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Beilstein J. Org. Chem. 2019, 15, 513–520, doi:10.3762/bjoc.15.45

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Conformational signature of Ishikawa´s reagent using NMR information from diastereotopic fluorines

Laize A. F. Andrade,
Lucas A. Zeoly,
Rodrigo A. Cormanich and
Matheus P. Freitas

Full Research Paper
Published 20 Feb 2019

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1. Graphical Abstract
2. Figure 1: Structure of Ishikawa´s reagent (1) and the respective Newman projections indicating the two key ro...
  
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3. Figure 2: Expansion of the ¹H and ¹⁹F NMR spectra in the region of CHF and CF₂, in C₆D₁₂ and C₅D₅N solvents. ...
  
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Beilstein J. Org. Chem. 2019, 15, 506–512, doi:10.3762/bjoc.15.44

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Synthesis and selected transformations of 2-unsubstituted 1-(adamantyloxy)imidazole 3-oxides: straightforward access to non-symmetric 1,3-dialkoxyimidazolium salts

Grzegorz Mlostoń,
Małgorzata Celeda,
Katarzyna Urbaniak,
Marcin Jasiński,
Vladyslav Bakhonsky,
Peter R. Schreiner and
Heinz Heimgartner

Full Research Paper
Published 19 Feb 2019

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1. Graphical Abstract
2. Scheme 1: Synthesis of 2-unsubstituted imidazole N-oxides 1 from α-hydroxyiminoketones 2 and formaldimines 3.
  
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3. Scheme 2: Preparation of adamantyloxyamine (4) and its conversion into N-(adamantyloxy)formaldimine (6a); Ad ...
  
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4. Scheme 3: Synthesis of 1-(adamantyloxy)imidazole 3-oxides 7a–e and 1-adamantylimidazole 3-oxides 7f,g in acet...
  
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5. Scheme 4: Deoxygenation of 1-(adamantyloxy)imidazole 3-oxides 7a–d and isomerization of 7b into imidazole-2-o...
  
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6. Scheme 5: Conversions of imidazole 3-oxides 7a–d into 1-(adamantyloxy)imidazole-2-thiones 10a–d via sulfur tr...
  
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7. Scheme 6: Syntheses of the non-symmetric 1,3-dialkoxyimidazolium bromides 13a–c and 1-alkyl-3-alkoxyimidazoli...
  
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8. Scheme 7: Attempted O-adamantylation of imidazole N-oxide 7a with adamantan-1-yl trifluoroacetate and subsequ...
  
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9. Scheme 8: Synthesis of the symmetric 1,3-di(adamantyloxy)imidazolium bromide (15) and its transformation to 1...
  
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Beilstein J. Org. Chem. 2019, 15, 497–505, doi:10.3762/bjoc.15.43

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A chemoenzymatic synthesis of ceramide trafficking inhibitor HPA-12

Seema V. Kanojia,
Sucheta Chatterjee,
Subrata Chattopadhyay and
Dibakar Goswami

Full Research Paper
Published 18 Feb 2019

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1. Graphical Abstract
2. Figure 1: Structure of most active HPA-12 isomers, originally proposed (1) and revised (2).
  
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3. Scheme 1: Lipase-catalyzed trans-acylation of (±)-4 and subsequent Mitsunobu inversion. Conditions: (i) Zn/TH...
  
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4. Scheme 2: Synthesis of azide 9 from (S)-4. Conditions: (i) NaH/Bu₄NI/BnBr/THF/25 °C/4 h; (ii) AD-mix-β/t-BuOH...
  
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5. Scheme 3: Attempted synthesis of 2 from 9. Conditions: (i) (a) LiAlH₄ (1 M in THF)/THF/25 °C/3 h, (b) DCC/DMA...
  
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6. Scheme 4: Actual synthesis of 2 from 9. Conditions: (i) DDQ/CH₂Cl₂–H₂O 4:1/3 h; (ii) a) LiAlH₄/THF/25 °C/3 h,...
  
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Beilstein J. Org. Chem. 2019, 15, 490–496, doi:10.3762/bjoc.15.42

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Synthesis and fluorescent properties of N(9)-alkylated 2-amino-6-triazolylpurines and 7-deazapurines

Andrejs Šišuļins,
Jonas Bucevičius,
Yu-Ting Tseng,
Irina Novosjolova,
Kaspars Traskovskis,
Ērika Bizdēna,
Huan-Tsung Chang,
Sigitas Tumkevičius and
Māris Turks

Full Research Paper
Published 15 Feb 2019

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1. Graphical Abstract
2. Figure 1: Examples of fluorescent purine/7-deazapurine derivatives.
  
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3. Scheme 1: General synthetic routes for the compounds 5, 7–9, 10 and 11. Method A: alkyl halogenide, MeCN or D...
  
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4. Figure 2: ¹H NMR spectra of compound 6b in CD₃CN at different temperatures (300 MHz, c = 12.5 mg/mL); a, b, c...
  
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5. Figure 3: Comparison of ¹H NMR spectra of compounds 8a and 5 (300 MHz, CDCl₃).
  
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6. Figure 4: a) Experimental UV–vis absorption spectra (lines) with computed theoretical absorption bands (colum...
  
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7. Figure 5: Photos of compound 8c (A and B) and compound 11c (C and D) in THF, CHCl₃, DMSO, MeCN and MeOH befor...
  
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8. Figure 6: a) Fluorescence spectra of compounds 8c (λ_exc = 360 nm) and 11c (λ_exc = 370 nm) in solvents of diff...
  
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9. Figure 7: Energy diagram for the frontier molecular orbitals of compounds 8a, 8c, 11a and 11c.
  
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10. Figure 8: Labeled MCF-7 cells using compound 9 (C,D) and unlabeled MCF-7 cells (A,B) in microscope (2 h, c(9)...
  
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Beilstein J. Org. Chem. 2019, 15, 474–489, doi:10.3762/bjoc.15.41

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Microwave-assisted synthesis of N,N-bis(phosphinoylmethyl)amines and N,N,N-tris(phosphinoylmethyl)amines bearing different substituents on the phosphorus atoms

Erika Bálint,
Anna Tripolszky,
László Hegedűs and
György Keglevich

Full Research Paper
Published 15 Feb 2019

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1. Graphical Abstract
2. Scheme 1: Synthesis of chiral thiazole-substituted aminophosphine oxides.
  
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3. Scheme 2: Synthesis of a P-chiral aminophosphine oxide containing a 2-pyridyl moiety.
  
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4. Scheme 3: Condensation of (octylaminomethyl)dihexylphosphine oxide with paraformaldehyde and di(p-tolyl)phosp...
  
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5. Scheme 4: Synthesis of (aminomethyl)phosphine oxides 5–7.
  
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6. Scheme 5: Synthesis of (aminomethyl)diphenylphosphine oxide (9).
  
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7. Scheme 6: Synthesis of N,N-bis(phosphinoylmethyl)amines 10a,b, 11a,b and 12a,b bearing different substituents...
  
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8. Scheme 7: Synthesis of N,N-bis(phosphinoylmethyl)amines 13a–c.
  
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9. Scheme 8: Synthesis of N,N,N-tris(phosphinoylmethyl)amines 14–17.
  
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Beilstein J. Org. Chem. 2019, 15, 469–473, doi:10.3762/bjoc.15.40

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Aqueous olefin metathesis: recent developments and applications

Valerio Sabatino and
Thomas R. Ward

Review
Published 14 Feb 2019

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1. Graphical Abstract
2. Scheme 1: Most common metathesis reactions. Ring-opening metathesis polymerization (ROMP), acyclic diene meta...
  
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3. Scheme 2: Catalytic cycle for metathesis proposed by Chauvin.
  
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4. Figure 1: Some of the most representative catalysts for aqueous metathesis. a) Well-defined ruthenium catalys...
  
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5. Scheme 3: First aqueous ROMP reactions catalyzed by ruthenium(III) salts.
  
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6. Scheme 4: Degradation pathway of first generation Grubbs catalyst (G-I) in methanol.
  
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7. Scheme 5: Synthesis of Blechert-type catalysts 19 and 20.
  
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8. Figure 2: Chemical structure and components of amphiphilic molecule PTS and derivatives.
  
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9. Scheme 6: RCM of selected substrates in the presence of the surfactant PTS. Conditions^a: The reaction was car...
  
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10. Scheme 7: RCM reactions of substrates 31 and 33 with the encapsulated G-II catalyst.
  
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11. Scheme 8: Living ROMP of norbornene derivatives 35 and 36 with phosphine-based catalysts bearing quaternary a...
  
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12. Scheme 9: Synthesis of water-soluble catalysts 3 and 4 bearing quaternary ammonium tags.
  
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13. Scheme 10: In situ formation of catalyst 5 bearing a quaternary ammonium group.
  
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14. Scheme 11: Catalyst recycling of an ammonium-bearing catalyst.
  
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15. Scheme 12: Removal of the water-soluble catalyst 12 through host–guest interaction with silica-gel-supported β...
  
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16. Scheme 13: Selection of artificial metathases reported by Ward and co-workers (ArM 1 based on biotin–(strept)a...
  
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17. Figure 3: In vivo metathesis with an artificial metalloenzyme based on the biotin–streptavidin technology.
  
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18. Scheme 14: Artificial metathase based on covalent anchoring approach. α-Chymotrypsin interacts with catalyst 66...
  
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19. Scheme 15: Assembling an artificial metathase (ArM 4) based on the small heat shock protein from M. Jannaschii...
  
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20. Scheme 16: Artificial metathases based on cavity-size engineered β-barrel protein nitrobindin (NB4exp). The HG...
  
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21. Scheme 17: Artificial metathase based on cutinase (ArM 8) and resulting metathesis activities.
  
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22. Scheme 18: Site-specific modification of proteins via aqueous cross-metathesis. The protein structure is based...
  
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23. Scheme 19: a) Allyl homocysteine (Ahc)-modified proteins as CM substrates. b) Incorporation of Ahc in the Fc p...
  
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24. Scheme 20: On-DNA cross-metathesis reaction of allyl sulfide 99.
  
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25. Scheme 21: Preparation of BODIPY-containing profluorescent probes 102 and 104.
  
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26. Scheme 22: Metathesis-based ethylene detection in live cells.
  
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27. Scheme 23: First example of stapled peptides via olefin metathesis.
  
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Beilstein J. Org. Chem. 2019, 15, 445–468, doi:10.3762/bjoc.15.39

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LCST phase behavior of benzo-21-crown-7 with different alkyl chains

Yan Deng,
Xing Li,
Qiao Zhang,
Zheng Luo,
Chengyou Han and
Shengyi Dong

Letter
Published 14 Feb 2019

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1. Graphical Abstract
2. Scheme 1: Chemical structures of 3a–e and 5a–e, and the cartoon representation of LCST behavior.
  
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3. Scheme 2: Synthetic routes and yields of 3a–e and 5a–e.
  
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4. Figure 1: ¹H NMR spectra (room temperature) of (a) 5a (5 mg/mL) in CDCl₃; (b) 5a (5 mg/mL) in D₂O; (c) 3a (5 ...
  
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5. Figure 2: a) Water solubility of 3a–e and 5a–e at room temperature; b) concentration-dependent LCST behavior ...
  
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6. Figure 3: Temperature-dependent ¹H NMR spectra (400 MHz, D₂O) of 3a–c and 5d. Measurement at temperature a) 2...
  
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Beilstein J. Org. Chem. 2019, 15, 437–444, doi:10.3762/bjoc.15.38

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

Arin Gucchait,
Angana Ghosh and
Anup Kumar Misra

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Published 13 Feb 2019

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1. Graphical Abstract
2. Figure 1: Structure of the synthesized pentasaccharide corresponding to the repeating unit of the biofilms pr...
  
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3. Scheme 1: Reagents and conditions: (a) i: Bu₂SnO, CH₃OH, 80 °C, 2 h; ii: allyl bromide, CsF, DMF, 65 °C, 6 h;...
  
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4. Scheme 2: Reagents and conditions: (a) Benzoyl chloride, pyridine, 0 °C, 3 h, 75%; (b) Tf₂O, BSP, TTBP, CH₂Cl₂...
  
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5. Scheme 3: Reagents and conditions: (a) TMSOTf, CH₂Cl₂, −10 °C, 30 min, 45%; (b) NIS, TMSOTf, MS 4 Å, CH₂Cl₂, ...
  
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6. Scheme 4: Reagents and conditions: (a) NIS, TMSOTf, MS 4 Å, CH₂Cl₂, −50 °C, 2 h, 70%; (b) benzyl bromide, NaO...
  
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Beilstein J. Org. Chem. 2019, 15, 431–436, doi:10.3762/bjoc.15.37

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