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Search for "lipophilicity" in Full Text gives 138 result(s) in Beilstein Journal of Organic Chemistry.
An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals
- Marcus Baumann,
- Ian R. Baxendale,
- Steven V. Ley and
- Nikzad Nikbin
Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57
- suffer from poor absorption and low bioavailability. At this stage a classical bioisostere exchange, i.e., replacing a carboxylic acid group with a tetrazole ring, was performed which resulted in increased lipophilicity [48] and the development of the orally active losartan. In the absence of a crystal
Graphical Abstract
Figure 1: Structures of atorvastatin and other commercial statins.
Figure 2: Structure of compactin.
Scheme 1: Synthesis of pentasubstituted pyrroles.
Scheme 2: [3 + 2] Cycloaddition to prepare 5-isopropylpyrroles.
Scheme 3: Regiospecific [3 + 2] cycloaddition to prepare the pyrrole scaffold.
Scheme 4: Formation of the pyrrole core of atorvastatin via [3 + 2] cycloaddition.
Scheme 5: Formation of pyrrole 33 via the Paal–Knorr reaction.
Scheme 6: Convergent synthesis towards atorvastatin.
Figure 3: Binding pocket of sunitinib in the TRK KIT.
Scheme 7: Synthesis of sunitinib.
Scheme 8: Alternative synthesis of sunitinib.
Scheme 9: Key steps in the syntheses of sumatriptan and zolmitriptan.
Scheme 10: Introduction of the N,N-dimethylaminoethyl side chain.
Scheme 11: Japp–Klingemann reaction in the synthesis of sumatriptan.
Scheme 12: Synthesis of the intermediate sulfonyl chlorides 62 and 63.
Scheme 13: Alternative introduction of the sulfonamide.
Scheme 14: Negishi-type coupling to benzylic sulfonamides.
Scheme 15: Heck reaction used to introduce the sulfonamide side chain of naratriptan.
Scheme 16: Synthesis of the oxazolinone appendage of zolmitriptan.
Scheme 17: Grandberg indole synthesis used in the preparation of rizatriptan.
Scheme 18: Improved synthesis of rizatriptan.
Scheme 19: Larock-type synthesis of rizatriptan.
Scheme 20: Synthesis of eletriptan.
Scheme 21: Heck coupling for the indole system in eletriptan.
Scheme 22: Attempted Fischer indole synthesis of elatriptan.
Scheme 23: Successful Fischer indole synthesis for eletriptan.
Scheme 24: Mechanistic rationale for the Bischler–Möhlau reaction.
Scheme 25: Bischler-type indole synthesis used in the fluvastatin sodium synthesis.
Scheme 26: Palladium-mediated synthesis of ondansetron.
Scheme 27: Fischer indole synthesis of ondansetron.
Scheme 28: Optimised Pictet–Spengler reaction towards tadalafil.
Figure 4: Structures of carvedilol 136 and propranolol 137.
Scheme 29: Synthesis of the carbazole core of carvedilol.
Scheme 30: Alternative syntheses of 4-hydroxy-9H-carbazole.
Scheme 31: Convergent synthesis of etodolac.
Scheme 32: Alternative synthesis of etodolac.
Figure 5: Structures of imidazole-containing drugs.
Scheme 33: Synthesis of functionalised imidazoles towards losartan.
Scheme 34: Direct synthesis of the chlorinated imidazole in losartan.
Scheme 35: Synthesis of trisubstituted imidazoles.
Scheme 36: Preparation of the imidazole ring in olmesartan.
Scheme 37: Synthesis of ondansetron.
Scheme 38: Alternative route to ondansetron and its analogues.
Scheme 39: Proton pump inhibitors and synthesis of esomeprazole.
Scheme 40: Synthesis of benzimidazole core pantoprazole.
Figure 6: Structure of rabeprazole 194.
Scheme 41: Synthesis of candesartan.
Scheme 42: Alternative access to the candesartan key intermediate 216.
Scheme 43: .Medicinal chemistry route to telmisartan.
Scheme 44: Improved synthesis of telmisartan.
Scheme 45: Synthesis of zolpidem.
Scheme 46: Copper-catalysed 3-component coupling towards zolpidem.
Figure 7: Structure of celecoxib.
Scheme 47: Preparation of celecoxib.
Scheme 48: Alternative synthesis of celecoxib.
Scheme 49: Regioselective access to celecoxib.
Scheme 50: Synthesis of pazopanib.
Scheme 51: Syntheses of anastrozole, rizatriptan and letrozole.
Scheme 52: Regioselective synthesis of anastrozole.
Scheme 53: Triazine-mediated triazole formation towards anastrozole.
Scheme 54: Alternative routes to 1,2,4-triazoles.
Scheme 55: Initial synthetic route to sitagliptin.
Figure 8: Binding of sitagliptin within DPP-IV.
Scheme 56: The process route to sitagliptin key intermediate 280.
Scheme 57: Synthesis of maraviroc.
Scheme 58: Synthesis of alprazolam.
Scheme 59: The use of N-nitrosoamidine derivatives in the preparation of fused benzodiazepines.
Figure 9: Structures of itraconazole, ravuconazole and voriconazole.
Scheme 60: Synthesis of itraconazole.
Scheme 61: Synthesis of rufinamide.
Scheme 62: Representative tetrazole formation in valsartan.
Figure 10: Structure of tetrazole containing olmesartan, candesartan and irbesartan.
Scheme 63: Early stage introduction of the tetrazole in losartan.
Scheme 64: Synthesis of cilostazol.
Figure 11: Structure of cefdinir.
Scheme 65: Semi-synthesis of cefdinir.
Scheme 66: Thiazole syntheses towards ritonavir.
Scheme 67: Synthesis towards pramipexole.
Scheme 68: Alternative route to pramipexole.
Scheme 69: Synthesis of famotidine.
Scheme 70: Efficient synthesis of the hyperuricemic febuxostat.
Scheme 71: Synthesis of ziprasidone.
Figure 12: Structure of mometasone.
Scheme 72: Industrial access to 2-furoic acid present in mometasone.
Scheme 73: Synthesis of ranitidine from furfuryl alcohol.
Scheme 74: Synthesis of nitrofurantoin.
Scheme 75: Synthesis of benzofuran.
Scheme 76: Synthesis of amiodarone.
Scheme 77: Synthesis of raloxifene.
Scheme 78: Alternative access to the benzo[b]thiophene core of raloxifene.
Scheme 79: Gewald reaction in the synthesis of olanzapine.
Scheme 80: Alternative synthesis of olanzapine.
Figure 13: Access to simple thiophene-containing drugs.
Scheme 81: Synthesis of clopidogrel.
Scheme 82: Pictet–Spengler reaction in the preparation of tetrahydrothieno[3,2-c]pyridine (422).
Scheme 83: Alternative synthesis of key intermediate 422.
Figure 14: Co-crystal structures of timolol (left) and carazolol (right) in the β-adrenergic receptor.
Scheme 84: Synthesis of timolol.
Scheme 85: Synthesis of tizanidine 440.
Scheme 86: Synthesis of leflunomide.
Scheme 87: Synthesis of sulfamethoxazole.
Scheme 88: Synthesis of risperidone.
Figure 15: Relative abundance of selected transformations.
Figure 16: The abundance of heterocycles within top 200 drugs (5-membered rings).
Synthesis of glycoconjugate fragments of mycobacterial phosphatidylinositol mannosides and lipomannan
- Benjamin Cao,
- Jonathan M. White and
- Spencer J. Williams
Beilstein J. Org. Chem. 2011, 7, 369–377, doi:10.3762/bjoc.7.47
- ) lipophilicity allowing biphasic partitioning between butanol/water or purification by reversed-phase extraction, (ii) ability to be reduced to an aminooctyl chain for use in squarate conjugation chemistry, and (iii) capacity to be conjugated with fluorescent terminal alkynes using the Cu(I)-catalyzed azide
Graphical Abstract
Scheme 1: Indicative topology model for the biosynthesis of the glycophospholipids PIMs, LM and LAM in mycoba...
Figure 1: Chemical structures of (A) a representative PIM, AcPIM5 and (B) a mannan fragment of LM from mycoba...
Figure 2: Target di- and trisaccharide glycoconjugate fragments of PIMs and LM.
Scheme 2: Synthesis of azidooctyl alcohol 14 and diol 15.
Scheme 3: Synthesis of mannosyl donors 16 and 17.
Figure 3: ORTEP plot of single crystal X-ray determination of (7S)-18. Thermal ellipsoids denote 20% electron...
Scheme 4: Synthesis of disaccharide 1 and trisaccharide 2.
Scheme 5: Synthesis of trisaccharide 3.
Scheme 6: Synthesis of trisaccharide 4.
Scheme 7: Synthesis of glycoconjugates 5–7 and 8–10.
Oxalyl retro-peptide gelators. Synthesis, gelation properties and stereochemical effects
- Janja Makarević,
- Milan Jokić,
- Leo Frkanec,
- Vesna Čaplar,
- Nataša Šijaković Vujičić and
- Mladen Žinić
Beilstein J. Org. Chem. 2010, 6, 945–959, doi:10.3762/bjoc.6.106
- explained by the increased lipophilicity of the diester derivatives and, consequently increased solubility in more lipophilic solvents compared to the diacid gelators. It should be noted that the diester racemates (S,R)-1b/(R,S)-1b and (S,S)-1b/(R,R)-1b showed significantly increased effectiveness in
Graphical Abstract
Scheme 1: Oxalyl retro-dipetide gelators; each b to a, (a) LiOH/MeOH, H2O; (b) H+; each b to c: (c) NH3/MeOH.
Figure 1: Chiral bis(amino acid)-(I) and bis(amino alcohol)-(II)-oxalamide gelators.
Figure 2: TEM images (PWK staining) of: (S,S)-1a H2O/DMSO gel.
Figure 3: TEM images (PWK staining) of: (S,R)-1a H2O/DMSO gel.
Figure 4: TEM images (PWK staining) of: (S,R)-1b toluene gel showing the presence of short tape like aggregat...
Figure 5: The concentration dependence of NH and C*H chemical shifts in (S,R)-1b toluene-d8 gel samples (conc...
Figure 6: The concentration dependence of NH and C*H chemical shifts in (S,S)-1b and its racemate (S,S)-1b/(R...
Figure 7: Temperature dependence of: a) oxalamide NH protons (▲), Leu-NH protons (Δ) and b) oxalamide-α-Leu-C...
Figure 8: Temperature dependent CD spectra of: a) (S,R)-1b decalin gel (c = 3.4·10−2 M); b) (S,S)-1b decalin ...
Figure 9: X-ray powder diffractograms of (a) (S,R)-1b and (b) (S,S)-1b xerogels prepared from their toluene g...
Figure 10: (a) Fully minimized the lowest energy conformations of (S,S)-1b (top) and (S,R)-1b generated by sys...
Figure 11: Schematic presentation of the proposed (S,S)-1b and (S,R)-1b basic packing model based on XRPD, 1H ...
Figure 12: X-ray powder diffraction (XRPD) diagram of (S,R)-1a water/DMSO xerogel.
Shelf-stable electrophilic trifluoromethylating reagents: A brief historical perspective
- Norio Shibata,
- Andrej Matsnev and
- Dominique Cahard
Beilstein J. Org. Chem. 2010, 6, No. 65, doi:10.3762/bjoc.6.65
- , chemical and biological properties [3]. The specific physical and chemical properties of fluorine in fluorine containing compounds, especially its strong electronegativity, lipophilicity and reaction ability, differ dramatically from those of other halogens and thus lead to changes in the interaction
Graphical Abstract
Scheme 1: Preparation of the first electrophilic trifluoromethylating reagent and its reaction with a thiophe...
Scheme 2: Synthetic routes to S-CF3 and Se-CF3 dibenzochalcogenium salts.
Scheme 3: Synthesis of (trifluoromethyl)dibenzotellurophenium salts.
Scheme 4: Nitration of (trifluoromethyl)dibenzochalcogenium salts.
Scheme 5: Synthesis of a sulphonium salt with a bridged oxygen.
Scheme 6: Reactivity of (trifluoromethyl)dibenzochalcogenium salts.
Scheme 7: Pd(II)-Catalyzed ortho-trifluoromethylation of heterocycle-substituted arenes by Umemoto’s reagents....
Scheme 8: Mild electrophilic trifluoromethylation of β-ketoesters and silyl enol ethers.
Scheme 9: Enantioselective electrophilic trifluoromethylation of β-ketoesters.
Scheme 10: Preparation of water-soluble S-(trifluoromethyl)dibenzothiophenium salts.
Scheme 11: Method for large-scale preparation of S-(trifluoromethyl)dibenzothiophenium salts.
Scheme 12: Triflic acid catalyzed synthesis of 5-(trifluoromethyl)thiophenium salts.
Scheme 13: Trifluoromethylation of β-ketoesters and dicyanoalkylidenes by S-(trifluoromethyl)benzothiophenium ...
Scheme 14: Synthesis of chiral S-(trifluoromethyl)benzothiophenium salt 18 and attempt of enantioselective tri...
Scheme 15: Synthesis of O-(trifluoromethyl)dibenzofuranium salts.
Scheme 16: Photochemical O- and N-trifluoromethylation by 20b.
Scheme 17: Thermal O-trifluoromethylation of phenol by diazonium salt 19a. Effect of the counteranion.
Scheme 18: Thermal O- and N-trifluoromethylations.
Scheme 19: Method of preparation of S-(trifluoromethyl)diphenylsulfonium triflates.
Scheme 20: Reactivity of some S-(trifluoromethyl)diarylsulfonium triflates.
Scheme 21: One-pot synthesis of S-(trifluoromethyl)diarylsulfonium triflates.
Scheme 22: One-pot synthesis of Umemoto’s type reagents.
Scheme 23: Preparation of sulfonium salts by transformation of CF3− into CF3+.
Scheme 24: Selected reactions with the new Yagupolskii reagents.
Scheme 25: Synthesis of heteroaryl-substituted sulfonium salts.
Scheme 26: First neutral S-CF3 reagents.
Scheme 27: Synthesis of Togni reagents. aYield for the two-step procedure.
Scheme 28: Trifluoromethylation of C-nucleophiles with 37.
Scheme 29: Selected examples of trifluoromethylation of S-nucleophiles with 37.
Scheme 30: Selected examples of trifluoromethylation of P-nucleophiles with 35 and 37.
Scheme 31: Trifluoromethylation of 2,4,6-trimethylphenol with 35.
Scheme 32: Examples of O-trifluoromethylation of alcohols with 35 in the presence of 1 equiv of Zn(NTf2)2.
Scheme 33: Formation of trifluoromethyl sulfonates from sulfonic acids and 35.
Scheme 34: Organocatalytic α-trifluoromethylation of aldehydes with 37.
Scheme 35: Synthesis of reagent 42 and mechanism of trifluoromethylation.
Scheme 36: Trifluoromethylation of β-ketoesters and dicyanoalkylidenes with 42.
Synthesis and crystallographic analysis of meso-2,3-difluoro-1,4-butanediol and meso-1,4-dibenzyloxy-2,3-difluorobutane
- Bruno Linclau,
- Leo Leung,
- Jean Nonnenmacher and
- Graham Tizzard
Beilstein J. Org. Chem. 2010, 6, No. 62, doi:10.3762/bjoc.6.62
- well as the lipophilicity, chemical and metabolic stability of the compound. Recent exciting reports describe weak but stabilising interactions between a C–F moiety and protein residues, which is certain to have implications in drug design [2][3]. Further important applications include molecular
Graphical Abstract
Figure 1: Vicinal difluoride containing building blocks.
Scheme 1: Synthesis of meso-2,3-difluoro-1,4-butanediol.
Scheme 2: Monoprotection of 3, and activation of the remaining alcohol.
Scheme 3: Reaction of 12 leading to defluorinated products.
Figure 2: Molecular overlay of both conformers of 7.
Figure 3: Crystal packing of 7 viewed along the b axis. Short contacts (see text) are shown in light blue.
Figure 4: Crystal structure of 3.
Figure 5: Crystal packing of 3 viewed along the c axis. H-bonds are shown in light blue.
Molecular recognition of organic ammonium ions in solution using synthetic receptors
- Andreas Späth and
- Burkhard König
Beilstein J. Org. Chem. 2010, 6, No. 32, doi:10.3762/bjoc.6.32
Graphical Abstract
Figure 1: Biologically important amines and quaternary ammonium salts: histamine (1), dopamine (2) and acetyl...
Figure 2: Crown ether 18-crown-6.
Figure 3: Conformations of 18-crown-6 (4) in solvents of different polarity.
Figure 4: Binding topologies of the ammonium ion depending on the crown ring size.
Figure 5: A “pseudorotaxane” structure consisting of 24-crown-8 and a secondary ammonium ion (5); R = Ph.
Figure 6: Typical examples of azacrown ethers, cryptands and related aza macrocycles.
Figure 7: Binding of ammonium to azacrown ethers and cryptands [111-113].
Figure 8: A 19-crown-6-ether with decalino blocking groups (11) and a thiazole-dibenzo-18-crown-6-ether (12).
Figure 9: 1,3-Bis(6-oxopyridazin-1-yl)propane derivatives 13 and 14 by Campayo et al.
Figure 10: Fluorescent azacrown-PET-sensors based on coumarin.
Figure 11: Two different pyridino-cryptands (17 and 18) compared to a pyridino-crown (19); chiral ammonium ion...
Figure 12: Pyridino-18-crown-6 ligand (21), a similar acridino-18-crown-6 ligand (22) and a structurally relat...
Figure 13: Ciral pyridine-azacrown ether receptors 24.
Figure 14: Chiral 15-crown-5 receptors 26 and an analogue 18-crown-6 ligand 27 derived from amino alcohols.
Figure 15: C2-symmetric chiral 18-crown-6 amino alcohol derivatives 28 and related macrocycles.
Figure 16: Macrocycles with diamide-diester groups (30).
Figure 17: C2-symmetric chiral aza-18-crown-6 ethers (31) with phenethylamine residues.
Figure 18: Chiral C-pivot p-methoxy-phenoxy-lariat ethers.
Figure 19: Chiral lariat crown ether 34.
Figure 20: Sucrose-based chiral crown ether receptors 36.
Figure 21: Permethylated fructooligosaccharide 37 showing induced-fit chiral recognition.
Figure 22: Biphenanthryl-18-crown-6 derivative 38.
Figure 23: Chiral lariat crown ethers derived from binol by Fuji et al.
Figure 24: Chiral phenolic crown ether 41 with “aryl chiral barriers” and guest amines.
Figure 25: Chiral bis-crown receptor 43 with a meso-ternaphthalene backbone.
Figure 26: Chromogenic pH-dependent bis-crown chemosensor 44 for diamines.
Figure 27: Triamine guests for binding to receptor 44.
Figure 28: Chiral bis-crown phenolphthalein chemosensors 46.
Figure 29: Crown ether amino acid 47.
Figure 30: Luminescent receptor 48 for bis-alkylammonium guests.
Figure 31: Luminescent CEAA (49a), a bis-CEAA receptor for amino acids (49b) and the structure of lysine bindi...
Figure 32: Luminescent CEAA tripeptide for binding small peptides.
Figure 33: Bis crown ether 51a self assembles co-operatively with C60-ammonium ion 51b.
Figure 34: Triptycene-based macrotricyclic dibenzo-[24]-crown-8 ether host 52 and guests.
Figure 35: Copper imido diacetic acid azacrown receptor 53a and the suggested His-Lys binding motif; a copper ...
Figure 36: Urea (54) and thiourea (55) benzo crown receptor for transport and extraction of amino acids.
Figure 37: Crown pyryliums ion receptors 56 for amino acids.
Figure 38: Ditopic sulfonamide bridged crown ether receptor 57.
Figure 39: Luminescent peptide receptor 58.
Figure 40: Luminescent receptor 59 for the detection of D-glucosamine hydrochloride in water/ethanol and lumin...
Figure 41: Guanidinium azacrown receptor 61 for simple amino acids and ditopic receptor 62 with crown ether an...
Figure 42: Chiral bicyclic guanidinium azacrown receptor 63 and similar receptor 64 for the enantioselective t...
Figure 43: Receptors for zwitterionic species based on luminescent CEAAs.
Figure 44: 1,10-Azacrown ethers with sugar podand arms and the anticancer agent busulfan.
Figure 45: Benzo-18-crown-6 modified β-cyclodextrin 69 and β-cyclodextrin functionalized with diaza-18-crown-6...
Figure 46: Receptors for colorimetric detection of primary and secondary ammonium ions.
Figure 47: Porphyrine-crown-receptors 72.
Figure 48: Porphyrin-crown ether conjugate 73 and fullerene-ammonium ion guest 74.
Figure 49: Calix[4]arene (75a), homooxocalix[4]arene (75b) and resorcin[4]arene (75c) compared (R = H, alkyl c...
Figure 50: Calix[4]arene and ammonium ion guest (R = H, alkyl, OAcyl etc.), possible binding sites; A: co-ordi...
Figure 51: Typical guests for studies with calixarenes and related molecules.
Figure 52: Lower rim modified p-tert-butylcalix[5]arenes 82.
Figure 53: The first example of a water soluble calixarene.
Figure 54: Sulfonated water soluble calix[n]arenes that bind ammonium ions.
Figure 55: Displacement assay for acetylcholine (3) with a sulfonato-calix[6]arene (84b).
Figure 56: Amino acid inclusion in p-sulfonatocalix[4]arene (84a).
Figure 57: Calixarene receptor family 86 with upper and lower rim functionalization.
Figure 58: Calix[6]arenes 87 with one carboxylic acid functionality.
Figure 59: Sulfonated calix[n]arenes with mono-substitution at the lower rim systematically studied on their r...
Figure 60: Cyclotetrachromotropylene host (91) and its binding to lysine (81c).
Figure 61: Calixarenes 92 and 93 with phosphonic acids groups.
Figure 62: Calix[4]arene tetraphosphonic acid (94a) and a double bridged analogue (94b).
Figure 63: Calix[4]arene tetraphosphonic acid ester (92c) for surface recognition experiments.
Figure 64: Calixarene receptors 95 with α-aminophosphonate groups.
Figure 65: A bridged homocalix[3]arene 95 and a distally bridged homocalix[4]crown 96.
Figure 66: Homocalix[3]arene ammonium ion receptor 97a and the Reichardt’s dye (97b) for colorimetric assays.
Figure 67: Chromogenic diazo-bridged calix[4]arene 98.
Figure 68: Calixarene receptor 99 by Huang et al.
Figure 69: Calixarenes 100 reported by Parisi et al.
Figure 70: Guest molecules for inclusion in calixarenes 100: DAP × 2 HCl (101a), APA (101b) and Lys-OMe × 2 HC...
Figure 71: Different N-linked peptido-calixarenes open and with glycol chain bridges.
Figure 72: (S)-1,1′-Bi-2-naphthol calixarene derivative 104 published by Kubo et al.
Figure 73: A chiral ammonium-ion receptor 105 based on the calix[4]arene skeleton.
Figure 74: R-/S-phenylalaninol functionalized calix[6]arenes 106a and 106b.
Figure 75: Capped homocalix[3]arene ammonium ion receptor 107.
Figure 76: Two C3 symmetric capped calix[6]arenes 108 and 109.
Figure 77: Phosphorous-containing rigidified calix[6]arene 110.
Figure 78: Calix[6]azacryptand 111.
Figure 79: Further substituted calix[6]azacryptands 112.
Figure 80: Resorcin[4]arene (75c) and the cavitands (113).
Figure 81: Tetrasulfonatomethylcalix[4]resorcinarene (114).
Figure 82: Resorcin[4]arenes (115a/b) and pyrogallo[4]arenes (115c, 116).
Figure 83: Displacement assay for acetylcholine (3) with tetracyanoresorcin[4]arene (117).
Figure 84: Tetramethoxy resorcinarene mono-crown-5 (118).
Figure 85: Components of a resorcinarene based displacement assay for ammonium ions.
Figure 86: Chiral basket resorcin[4]arenas 121.
Figure 87: Resorcinarenes with deeper cavitand structure (122).
Figure 88: Resorcinarene with partially open deeper cavitand structure (123).
Figure 89: Water-stabilized deep cavitands with partially structure (124, 125).
Figure 90: Charged cavitands 126 for tetralkylammonium ions.
Figure 91: Ditopic calix[4]arene receptor 127 capped with glycol chains.
Figure 92: A calix[5]arene dimer for diammonium salt recognition.
Figure 93: Calixarene parts 92c and 129 for the formation molecular capsules.
Figure 94: Encapsulation of a quaternary ammonium cation by two resorcin[4]arene molecules (NMe4+@[75c]2 × Cl−...
Figure 95: Encapsulation of a quaternary ammonium cation by six resorcin[4]arene molecules (NMe3D+@[130]6 × Cl−...
Figure 96: Structure and schematic of cucurbit[6]uril (CB[6], 131a).
Figure 97: Cyclohexanocucurbit[6]uril (CB′[6], 132) and the guest molecule spermine (133).
Figure 98: α,α,δ,δ-Tetramethylcucurbit[6]uril (134).
Figure 99: Structure of the cucurbituril-phthalhydrazide analogue 135.
Figure 100: Organic cavities for the displacement assay for amine differentiation.
Figure 101: Displacement assay methodology for diammonium- and related guests involving cucurbiturils and some ...
Figure 102: Nor-seco-Cucurbituril (±)-bis-ns-CB[6] (140) and guest molecules.
Figure 103: The cucurbit[6]uril based complexes 141 for chiral discrimination.
Figure 104: Cucurbit[7]uril (131c) and its ferrocene guests (142) opposed.
Figure 105: Cucurbit[7]uril (131c) guest inclusion and representative guests.
Figure 106: Cucurbit[7]uril (131c) binding to succinylcholine (145) and different bis-ammonium and bis-phosphon...
Figure 107: Paraquat-cucurbit[8]uril complex 149.
Figure 108: Gluconuril-based ammonium receptors 150.
Figure 109: Examples of clefts (151a), tweezers (151b, 151c, 151d) and clips (151e).
Figure 110: Kemp’s triacid (152a), on example of Rebek’s receptors (152b) and guests.
Figure 111: Amino acid receptor (154) by Rebek et al.
Figure 112: Hexagonal lattice designed hosts by Bell et al.
Figure 113: Bell’s amidinium receptor (156) and the amidinium ion (157).
Figure 114: Aromatic phosphonic acids.
Figure 115: Xylene phosphonates 159 and 160a/b for recognition of amines and amino alcohols.
Figure 116: Bisphosphonate recognition motif 161 for a colorimetric assay with alizarin complexone (163) for ca...
Figure 117: Bisphosphonate/phosphate clip 164 and bisphosphonate cleft 165.
Figure 118: N-Methylpyrazine 166a, N-methylnicotinamide iodide (166b) and NAD+ (166c).
Figure 119: Bisphosphate cavitands.
Figure 120: Bisphosphonate 167 of Schrader and Finocchiaro.
Figure 121: Tweezer 168 for noradrenaline (80b).
Figure 122: Different tripods and heparin (170).
Figure 123: Squaramide based receptors 172.
Figure 124: Cage like NH4+ receptor 173 of Kim et al.
Figure 125: Ammonium receptors 174 of Chin et al.
Figure 126: 2-Oxazolin-based ammonium receptors 175a–d and 176 by Ahn et al.
Figure 127: Racemic guest molecules 177.
Figure 128: Tripods based on a imidazole containing macrocycle (178) and the guest molecules employed in the st...
Figure 129: Ammonium ion receptor 180.
Figure 130: Tetraoxa[3.3.3.3]paracyclophanes 181 and a cyclophanic tetraester (182).
Figure 131: Peptidic bridged paraquat-cyclophane.
Figure 132: Shape-selective noradrenaline host.
Figure 133: Receptor 185 for binding of noradrenaline on surface layers from Schrader et al.
Figure 134: Tetraphosphonate receptor for binding of noradrenaline.
Figure 135: Tetraphosphonate 187 of Schrader and Finocchiaro.
Figure 136: Zinc-Porphyrin ammonium-ion receptors 188 and 189 of Mizutani et al.
Figure 137: Zinc porphyrin receptor 190.
Figure 138: Zinc porphyrin receptors 191 capable of amino acid binding.
Figure 139: Zinc-porphyrins with amino acid side chains for stereoinduction.
Figure 140: Bis-zinc-bis-porphyrin based on Tröger’s base 193.
Figure 141: BINAP-zinc-prophyrin derivative 194 and it’s guests.
Figure 142: Bisaryl-linked-zinc-porphyrin receptors.
Figure 143: Bis-zinc-porphyrin 199 for diamine recognition and guests.
Figure 144: Bis-zinc-porphyrin crown ether 201.
Figure 145: Bis-zinc-porphyrin 202 for stereodiscrimination (L = large substituent; S = small substituent).
Figure 146: Bis-zinc-porphyrin[3]rotaxane and its copper complex and guests.
Figure 147: Dien-bipyridyl ligand 206 for co-ordination of two metal atoms.
Figure 148: The ligand and corresponding tetradentate co-complex 207 serving as enantioselective receptor for a...
Figure 149: Bis(oxazoline)–copper(II) complex 208 for the recognition of amino acids in aqueous solution.
Figure 150: Zinc-salen-complexes 209 for the recognition tertiary amines.
Figure 151: Bis(oxazoline)–copper(II) 211 for the recognition of amino acids in aqueous solution.
Figure 152: Zn(II)-complex of a C2 terpyridine crown ether.
Figure 153: Displacement assay and receptor for aspartate over glutamate.
Figure 154: Chiral complex 214 for a colorimetric displacement assay for amino acids.
Figure 155: Metal complex receptor 215 with tripeptide side arms.
Figure 156: A sandwich complex 216 and its displaceable dye 217.
Figure 157: Lanthanide complexes 218–220 for amino acid recognition.
Figure 158: Nonactin (221), valinomycin (222) and vancomycin (223).
Figure 159: Monesin (224a) and a chiral analogue for enantiodiscrimination of ammonium guests (224b).
Figure 160: Chiral podands (226) compared to pentaglyme-dimethylether (225) and 18-crown-6 (4).
Figure 161: Lasalocid A (228).
Figure 162: Lasalocid derivatives (230) of Sessler et al.
Figure 163: The Coporphyrin I tetraanion (231).
Figure 164: Linear and cyclic peptides for ammonium ion recognition.
Figure 165: Cyclic and bicyclic depsipeptides for ammonium ion recognition.
Figure 166: α-Cyclodextrin (136a) and novocaine (236).
Figure 167: Helical diol receptor 237 by Reetz and Sostmann.
Figure 168: Ammonium binding spherand by Cram et al. (238a) and the cyclic[6]metaphenylacetylene 238b in compar...
Figure 169: Receptor for peptide backbone and ammonium binding (239).
Figure 170: Anion sensor principle with 3-hydroxy-2-naphthanilide of Jiang et al.
Figure 171: 7-bromo-3-hydroxy-N-(2-hydroxyphenyl)naphthalene 2-carboxamide (241) and its amine binding.
Figure 172: Naturally occurring catechins with affinity to quaternary ammonium ions.
Figure 173: Spiropyran (244) and merocyanine form (244a) of the amino acid receptors of Fuji et al.
Figure 174: Coumarin aldehyde (245) and its iminium species with amino acid bound (245a) by Glass et al.
Figure 175: Coumarin aldehyde appended with boronic acid.
Figure 176: Quinolone aldehyde dimers by Glass et al.
Figure 177: Chromogenic ammonium ion receptors with trifluoroacetophenone recognition motifs.
Figure 178: Chromogenic ammonium ion receptor with trifluoroacetophenone recognition motif bound on different m...
Synthesis of lipophilic 1-deoxygalactonojirimycin derivatives as D-galactosidase inhibitors
- Georg Schitter,
- Elisabeth Scheucher,
- Andreas J. Steiner,
- Arnold E. Stütz,
- Martin Thonhofer,
- Chris A. Tarling,
- Stephen G. Withers,
- Jacqueline Wicki,
- Katrin Fantur,
- Eduard Paschke,
- Don J. Mahuran,
- Brigitte A. Rigat,
- Michael Tropak and
- Tanja M. Wrodnigg
Beilstein J. Org. Chem. 2010, 6, No. 21, doi:10.3762/bjoc.6.21
- losses during column chromatography. For increased lipophilicity as well as for analytical purposes, compound 15 was also coupled to 1-pyrenebutyric acid with TBTU in DMF in the presence of triethylamine to give compound 19 in 56% yield. The pyrenyl substituent was chosen because of its potential to
Graphical Abstract
Figure 1: Typical representatives of iminosugars.
Figure 2: N-Modified iminosugars 5–9 as potential pharmacological chaperones.
Figure 3: Structure of NOEV 10.
Scheme 1: Three-step-synthesis of partially protected 1-deoxy-D-galactonojirimycin derivative 12 from 10 via ...
Scheme 2: Synthesis of N-(6-aminohexyl)-1-deoxygalactonojirimycin (15) from 12 via 14.
Scheme 3: Synthesis of lipophilic 1-deoxy-D-galactonojirimycin derivatives 16–18 by chemoselective acylation ...
Scheme 4: Synthesis of compounds 19 as well as 20 from primary amine 15.
Scheme 5: Synthesis of compound 22.
Enantioselective nucleophilic difluoromethylation of aromatic aldehydes with Me3SiCF2SO2Ph and PhSO2CF2H reagents catalyzed by chiral quaternary ammonium salts
- Chuanfa Ni,
- Fang Wang and
- Jinbo Hu
Beilstein J. Org. Chem. 2008, 4, No. 21, doi:10.3762/bjoc.4.21
- this field. Background Because of the unique properties of fluorine, selective introduction of fluorine atom(s) or fluorine-containing moieties into organic molecules often dramatically alter their stability, lipophilicity, bioavailability, and biopotency. It is estimated that as many as 30–40% of
Graphical Abstract
Scheme 1: Structure of chiral quaternary ammonium salts.
Scheme 2: Determination of the absolute configuration of (+)-3a.
Understanding the mechanism of Pd-catalyzed allylic substitution of the cyclic difluorinated carbonates
- Jun Xu,
- Xiao-Long Qiu and
- Feng-Ling Qing
Beilstein J. Org. Chem. 2008, 4, No. 18, doi:10.3762/bjoc.4.18
- phosphorylases and higher lipophilicity, two properties that are potentially beneficial in terms of increased in vivo half life, oral efficiency and cell wall penetration [1][2]. Based on CNA skeletons, 1,2-disubstituted carbocyclic nucleosides (OTCs) recently attracted more and more attention [3][4][5][6][7][8
Graphical Abstract
Scheme 1: Pd-catalyzed allylic substitution of the gem-difluorinated allylic carbonates 1 and 4.
Scheme 2: Synthesis of trans-trans dimer 8 and syn-syn dimer 9.
Figure 1: X-ray structure of trans-trans dimer 8.
Scheme 3: Reaction of trans-trans dimer 8 with 3-benzoylthymine sodium / PPh3.
Scheme 4: Reaction of trans-trans dimer 8 with PPh3 / AgSbF6.
Trifluoromethyl ethers – synthesis and properties of an unusual substituent
- Frédéric R. Leroux,
- Baptiste Manteau,
- Jean-Pierre Vors and
- Sergiy Pazenok
Beilstein J. Org. Chem. 2008, 4, No. 13, doi:10.3762/bjoc.4.13
- latter are unfavorable all alternative mechanisms avoiding attack at fluorine always apply in biological systems [4]. Moreover, the presence of fluorine atoms in biologically active molecules can enhance their lipophilicity and thus their in vivo uptake and transport. In particular, the trifluoromethyl
- group (−CF3) confers increased stability and lipophilicity in addition to its high electronegativity [5][6][7][8][9]. However, another fluorinated substituent, the trifluoromethoxy group, is becoming more and more important in both agrochemical research and pharmaceutical chemistry [10][11]. The
- : 36°) [51]. Lipophilicity On the basis of its electronic properties, which are close to those of a chlorine or a fluorine atom [52], the trifluoromethoxy group has been referred to as a super- [53] or a pseudo-halogen [54]. The advantage of incorporating a trifluoromethoxy group into a molecule can be
Graphical Abstract
Figure 1: OCF3-bearing pesticides.
Scheme 1: Preparation of trifluoromethyl ethers via a chlorination/fluorination sequence.
Scheme 2: Preparation of trifluoromethyl ethers via an in situ chlorination/fluorination sequence.
Scheme 3: Preparation of trifluoromethyl ethers via chlorothionoformates.
Scheme 4: Preparation of trifluoromethyl ethers via fluoroformates.
Scheme 5: Oxidative desulfurization-fluorination toward trifluoromethyl ethers.
Scheme 6: Mechanism of the oxidative desulfurization-fluorination.
Scheme 7: Umemoto's O-(trifluoromethyl)dibenzofuranium salts 4 as CF3-transfer agents.
Scheme 8: Togni's approach using hypervalent iodine compounds as CF3-transfer agents.
Scheme 9: TAS OCF3 as a nucleophilic OCF3-transfer agent.
Figure 2: Mesomeric structures of the OCF3-group.
Figure 3: Structures of 6 and 7.
Figure 4: Conformational preference of the trifluoromethoxy group on aryl rings.
Scheme 10: Nitration of trifluoromethoxy benzene.
Scheme 11: Synthesis and Nitration of N-Acetyl-(trifluoromethoxy)anilines.
Scheme 12: Bromine/lithium exchange of bromo(trifluoromethoxy)benzenes.
Scheme 13: Metalation of (trifluoromethoxy)benzene.
Scheme 14: Metalation of (trifluoromethoxy)naphthalenes.
Scheme 15: Competition between -CF3- and -OCF3 in Metalation reactions.
Scheme 16: Competition between -F- and -OCF3 in Metalation reactions.
Scheme 17: Metalation of trifluoromethoxyanisoles.
Figure 5: Direction of π-polarization depending on the substituent as described by Schlosser et al. [57].
Scheme 18: Metalation of Bromo(trifluoromethoxy)benzenes.
Scheme 19: Aryne formation from bromo(trifluoromethoxy)phenyllithiums and subsequent Diels-Alder cycloaddition...
Scheme 20: Metalation of (trifluoromethoxy)anilines.
Cimicifoetisides A and B, two cytotoxic cycloartane triterpenoid glycosides from the rhizomes of Cimicifuga foetida, inhibit proliferation of cancer cells
- Li-Rong Sun,
- Chen Qing,
- Yan-Li Zhang,
- Shu-Yu Jia,
- Zhong-Rong Li,
- Shen-Ji Pei,
- Ming-Hua Qiu,
- Michael L. Gross and
- Samuel X. Qiu
Beilstein J. Org. Chem. 2007, 3, No. 3, doi:10.1186/1860-5397-3-3
- higher lipophilic nature of triterpene glycosides could be critical to the cytotoxicity as observed for 1 and 2 whose cytotoxicity are proportional to their lipophilicity (vs. cimigenol 3-O-β-D-xylopyranoside, which is devoid of appreciable activity) with the introduction of acetyl groups. Interestingly
Graphical Abstract
Figure 1: Compounds 1 and 2 isolated from Cimicifuga foetida. 1. R1 = 2'-O-acetylarabinosyl, R2 = H; 2. R1 = ...
Figure 2: Key long-range 13C-1H correlations of 1 observed by HMBC.
Figure 3: Key long-range 13C-1H correlations of 2 observed by HMBC for the relevant carbons with the acetyl g...
Study of thioglycosylation in ionic liquids
- Jianguo Zhang and
- Arthur Ragauskas
Beilstein J. Org. Chem. 2006, 2, No. 12, doi:10.1186/1860-5397-2-12
- species, as shown in Figure 1. A broader spectrum of anionic counter ions have been reported, including: halides, carbonates, sulfonates, tetrafluorborates, nitrates and chloroaluminates. Changes in the physical properties of ionic liquids, including their melting point, hydrophilicity, lipophilicity and
Graphical Abstract
Figure 1: Structures of common ionic liquids.
Scheme 1: Glycosylation of 1 and 2 with various glycosyl donors.
Synthesis of novel (1-alkanoyloxy- 4-alkanoylaminobutylidene)-1,1-bisphosphonic acid derivatives
- Petri A. Turhanen and
- Jouko J. Vepsäläinen
Beilstein J. Org. Chem. 2006, 2, No. 2, doi:10.1186/1860-5397-2-2
- hydrophilic, highly anionic and their bioavailabilities are very poor. [12][13][14] It would be a clear advance to prepare more lipophilic and biodegradable derivatives of BPs. A rather straightforward method to improve the lipophilicity of amino BPs is to convert hydroxyl or/and amino group or the phosphonic
Graphical Abstract
Figure 1:
Scheme 1: Preparation of (1-alkanoyloxy-4-alkanoylaminobutylidene)-1,1-bisphosphonic acid derivatives 1a (R =...
