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Search for "glutamate" in Full Text gives 60 result(s) in Beilstein Journal of Organic Chemistry.
An intramolecular inverse electron demand Diels–Alder approach to annulated α-carbolines
- Zhiyuan Ma,
- Feng Ni,
- Grace H. C. Woo,
- Sie-Mun Lo,
- Philip M. Roveto,
- Scott E. Schaus and
- John K. Snyder
Beilstein J. Org. Chem. 2012, 8, 829–840, doi:10.3762/bjoc.8.93
- grossularia (Stylidae) [1][2], and desmethylgrossularine-1 from tunicate Polycarpa aurata [3]. Other natural α-carbolines include mescengricin (3), an inhibitor of L-glutamate excitotoxicity in neutrons, isolated from Streptomyces griseoflavus [4], and cryptotackieine (4) [5], also known as neocryptolepine [6
Graphical Abstract
Figure 1: Natural products with α-carboline subunits.
Scheme 1: Retrosynthetic inverse electron Diels–Alder approach to α-carbolines.
Scheme 2: Condensation of isatins with ethyl oxaloamidrazonate to form triazines.
Scheme 3: Amidation of triazine ester 8a.
Scheme 4: Microwave-promoted IEDDA reaction of isatin derived triazines.
Scheme 5: One-pot amidation/cycloaddition of triazine ester 8a.
Scheme 6: Amidation/cycloaddition forming α-carbolines 14.
Scheme 7: Intramolecular hydrogen bonding prevents IEDDA cycloaddition of 14b.
Scheme 8: Preparation of unprotected triazine 15, and its lack of reactivity in cycloadditions.
Scheme 9: Transesterification and subsequent cycloaddition of 17a.
Synthesis of highly functionalized β-aminocyclopentanecarboxylate stereoisomers by reductive ring opening reaction of isoxazolines
- Melinda Nonn,
- Loránd Kiss,
- Reijo Sillanpää and
- Ferenc Fülöp
Beilstein J. Org. Chem. 2012, 8, 100–106, doi:10.3762/bjoc.8.10
- bioactive derivatives in organic and medicinal chemistry (e.g., conformationally restricted aspartate and glutamate analogues) [1][2][3][4][5][6]. As a consequence of their ability to undergo reductive ring opening, isoxazolines are of interest as precursors for the synthesis of highly functionalized
Graphical Abstract
Figure 1: Structures of neuraminidase inhibitors.
Scheme 1: Isoxazoline-fused β-aminocyclopentanecarboxylate regio- and stereoisomers [8].
Scheme 2: Treatment of isoxazoline-fused amino ester 2 with NaBH4.
Scheme 3: Reduction with Pd/C in the presence of HCO2NH4.
Scheme 4: Transformation of isoxazoline-fused cispentacin stereoisomer 2 into multifunctionalized β-amino aci...
Figure 2: ORTEP diagram of 12 showing the atomic labeling scheme. The thermal ellipsoids are drawn at the 20%...
Scheme 5: Synthesis of multifunctionalized β-amino acid derivatives 13–16. Reaction conditions: NaBH4, NiCl2,...
Natural product biosyntheses in cyanobacteria: A treasure trove of unique enzymes
- Jan-Christoph Kehr,
- Douglas Gatte Picchi and
- Elke Dittmann
Beilstein J. Org. Chem. 2011, 7, 1622–1635, doi:10.3762/bjoc.7.191
- , microcystins contain two amino acids that are linked with their ω-carboxy group in the peptide chain, namely glutamate and aspartate. Although the mechanism by which these amino acids are activated is still unknown, the microcystin biosynthesis pathway exemplifies the high number of unique features in
- Microcystis and Planktothrix [64][65]. Post-translational modification of microviridins is achieved by the activity of two closely related ATP grasp ligases, MdnB and MdnC (MvdC and D in Planktothrix). The enzymes introduce two ω-ester linkages between threonine and aspartate and serine and glutamate (MdnC
Graphical Abstract
Figure 1: Cyanobacteria proliferate in diverse habitats. A) Bloom-forming freshwater cyanobacteria of the gen...
Figure 2: Schematic representation of enzymatic domains in A) nonribosomal peptide synthetases (NRPS); B) pol...
Figure 3: Structures of NRPS and PKS products in freshwater cyanobacteria.
Figure 4: A) Synthesis of the Adda ((2S,3S,8S,9S)-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyl-4,6-decadienoic...
Figure 5: Structures of NRPS and PKS products in marine cyanobacteria.
Figure 6: A) Formation of the trichloroleucyl starter unit of barbamide (7) synthesis through the non-heme ir...
Figure 7: Structures of NRPS and PKS products in terrestrial cyanobacteria.
Figure 8: Synthesis of the (2S,4S)-4-methylproline moiety of nostopeptolides A (13).
Figure 9: Structures of cyanobacterial peptides that are synthesized ribosomally and post-translationally mod...
Figure 10: Formation of ester linkages and ω-amide linkage in microviridins 17 by the ATP grasp ligases MvdD a...
Figure 11: Structures of cyanobacterial sunscreen compounds.
Coupled chemo(enzymatic) reactions in continuous flow
- Ruslan Yuryev,
- Simon Strompen and
- Andreas Liese
Beilstein J. Org. Chem. 2011, 7, 1449–1467, doi:10.3762/bjoc.7.169
- tested in the continuous simultaneous synthesis of gluconic acid (9) and glutamic acid (8) by coupling the NADP+-dependent glucose (7) oxidation catalyzed by glucose oxidase with the reductive amination of α-ketoglutaric acid (6) catalyzed by glutamate dehydrogenase (Scheme 3). When the process was
- -(−)-Mandelic acid dehydrogenase; E2: Formate dehydrogenase [23]. Simultaneous synthesis of gluconic acid (9) and glutamic acid (8) in a continuously operated membrane reactor. E1: Glutamate dehydrogenase; E2: Glucose oxidase [24]. Production of L-tert-leucine (11) in a continuously operated enzyme membrane
Graphical Abstract
Figure 1: Metabolic pathways in a living cell as an example of efficient coupled-reaction processes. A: Subst...
Figure 2: Four generations of biotransformations. I: Single-reaction processes; II: Single-reaction processes...
Scheme 1: Production of L-leucine (3) in a continuously operating enzyme membrane reactor (EMR). E1: L-Leucin...
Scheme 2: Production of D-mandelic acid (5) in a continuously operating enzyme membrane reactor. E1: D-(−)-Ma...
Scheme 3: Simultaneous synthesis of gluconic acid (9) and glutamic acid (8) in a continuously operated membra...
Scheme 4: Production of L-tert-leucine (11) in a continuously operated enzyme membrane reactor equipped with ...
Scheme 5: Continuous oxidation of lactose (12) to lactobionic acid (13) in a dynamic membrane-aerated reactor...
Scheme 6: Production of N-acetylneuraminic acid (17) in a continuously operated enzyme membrane reactor. E1: ...
Scheme 7: Chemo-enzymatic epoxidation of 1-methylcyclohexene (18) in a packed-bed reactor (PBR) containing No...
Scheme 8: Continuous production of (R)-1-phenylethyl propionate (24) by dynamic kinetic resolution of (rac)-1...
Scheme 9: Synthesis of D-xylulose (28) from D,L-serine (26) and D,L-glyceraldehyde (25) in a continuously ope...
Scheme 10: Continuous production of L-alanine (31) from fumarate (29) in a two-stage enzyme membrane reactor. ...
Scheme 11: Continuous synthesis of 1-phenyl-(1S,2S)-propanediol (35) in a cascade of two enzyme membrane react...
Scheme 12: Production of a dipeptide 39 in a cascade of two continuously operated membrane reactors. E1: Carbo...
Scheme 13: Continuous production of GDP-mannose (43) from mannose 1-phosphate (40) in a cascade of two enzyme ...
Scheme 14: Continuous solvent-free chemo-enzymatic synthesis of ethyl (S)-3-(benzylamino)butanoate (48) in a s...
Scheme 15: Continuous chemo-enzymatic synthesis of grossamide (52) in a cascade of packed-bed reactors. E: Per...
Scheme 16: Chemo-enzymatic synthesis of 2-aminophenoxazin-3-one (56) in a cascade of continuously operating pa...
Scheme 17: Continuous conversion of 3-phospho-D-glycerate (57) into D-ribulose 1,5-bisphosphate (58) in a casc...
Scheme 18: Continuous hydrolysis of 4-cyanopyridine (59) to isonicotinic acid (61) in a cascade of two packed-...
Scheme 19: Continuous fermentative production of ethanol (64) from hardwood lignocellulose (62) in a stirred-t...
Scheme 20: Production of hydrogen by anaerobic fermentation of glucose (7) using Clostridium acetobutylicum ce...
Scheme 21: Continuous production of (2R,5R)-hexanediol (67) in an enzyme membrane reactor containing whole cel...
Scheme 22: Synthesis of L-phenylalanine (69) in a continuously stirred tank reactor equipped with a hollow-fib...
Scheme 23: Continuous epoxidation of 1,7-octadiene (70) to (R)-7-epoxyoctene (72) by a strain of Pseudomonas o...
Scheme 24: Oxidation of styrene (73) to (S)-styrene oxide (74) in a continuously operated biofilm tube reactor...
Scheme 25: Reduction of estrone (75) to β-estradiol (76) by Saccharomyces cerevisiae in a cascade of two stirr...
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
- normally filled by the ADP’s adenine in the phosphorylated protein. The indolinone section is located in a deeper pocket with the heteroatoms being involved in H-bonding glutamate and tyrosine residues whilst the pyrrole ring and the diethylaminoethyl appendage are exposed to the solvent environment [8
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).
pH-Responsive chromogenic-sensing molecule based on bis(indolyl)methene for the highly selective recognition of aspartate and glutamate
- Litao Wang,
- Xiaoming He,
- Yong Guo,
- Jian Xu and
- Shijun Shao
Beilstein J. Org. Chem. 2011, 7, 218–221, doi:10.3762/bjoc.7.29
- Academy of Sciences, Beijing 100039, P. R. China 10.3762/bjoc.7.29 Abstract Bis(indolyl)methene displays high selectivity and sensitivity for aspartate and glutamate in water-containing medium based on the proton transfer signaling mode. The presence of acid can easily induce proton transfer to the basic
- H-bond acceptor moiety, which modulates the internal charge transfer state of the bis(indolyl)methene skeleton and gives rise to dramatic change in color. The detection limits for aspartate and glutamate were 0.80 ppm and 1.12 ppm, respectively. Keywords: aspartate and glutamate; bis(indolyl
- shown that aspartate (Asp) and glutamate (Glu) are important neurotransmitters [9][10][11], thus the recognition or sensing of these amino acids by synthetic receptor molecules is of great interest [12][13][14]. The bis(indolyl)methene molecule 1 (Figure 1), possessing an acidic H-bond donor moiety and
Graphical Abstract
Figure 1: Structure of sensor 1.
Figure 2: Changes in UV–vis spectra of 1 (5.0 × 10−5 M) after addition of: (a) 0–0.10 mL H2O; (b) various rat...
Figure 3: pH-dependent changes in UV–vis spectra of 1 (5.0 × 10−5 M) in CH3CN/H2O (1:1, v/v) at (a) pH = 1–7,...
Figure 4: Changes in UV–vis spectra of 1 (5.0 × 10−5 M) in CH3CN/H2O (1:1, v/v) after addition of: (a) 25 equ...
An easy assembled fluorescent sensor for dicarboxylates and acidic amino acids
- Xiao-bo Zhou,
- Yuk-Wang Yip,
- Wing-Hong Chan and
- Albert W. M. Lee
Beilstein J. Org. Chem. 2011, 7, 75–81, doi:10.3762/bjoc.7.11
- for sensing dicarboxylates. Their binding affinities toward dicarboxylates, aspartate and glutamate have been investigated in acetonitrile solution by fluorescence titration experiments. Both fluorescent sensors exhibited some ability to discriminate the antipodal forms of aspartate and glutamate
- present in aspartates weakened their interaction with sensor 1, presumably due to non-bonding repulsions. In contrast, in comparison with the association constant between sensor 1 and glutarate, sensor 1 exhibited a stronger binding affinity to D- and L-glutamate (Table 2). Interestingly, a marginal
- enantioselectivity toward the antipodal forms of aminoacids demonstrated by sensor 1 is evident. We were aware that sensor 1 can only exhibit two-point interaction with aspartate and glutamate via the thiourea–carboxylate type of binding motif. For the host to exert a greater influence on the preorganization of the
Graphical Abstract
Scheme 1: Synthesis of sensor 1 and 2.
Figure 1: The changes in the fluorescence emission spectra of sensor 1 (5.0 × 10−6 M) upon addition of isopht...
Figure 2: Proposed three sites binding model for sensor 2 and glutamate complex.
Figure 3: Partial 1H NMR spectra for (a) sensor 2 (free, 3 mM), (b) sensor 2 + 0.5 equiv D-glutamate, (c) sen...
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 and enzymatic evaluation of 2- and 4-aminothiazole- based inhibitors of neuronal nitric oxide synthase
- Graham R. Lawton,
- Haitao Ji,
- Pavel Martásek,
- Linda J. Roman and
- Richard B. Silverman
Beilstein J. Org. Chem. 2009, 5, No. 28, doi:10.3762/bjoc.5.28
- partially charged in biological systems. Crystal structures of 2 bound to the active site of nNOS show that the aminopyridine group interacts with a glutamate residue (Glu592, rat nNOS), presumably via hydrogen bonding and electrostatic interactions [8][12]. The aminopyridine ring nitrogen must be
- site, however, protonation should occur to allow the aminothiazole to interact with the active site glutamate and maintain tight binding. The methyl group at the 4 position on the aminopyridine ring contributes to binding through an interaction with a hydrophobic pocket in the nNOS active site. The R
- the glutamate. We had hoped that the high acidity of the active site would protonate the aminothiazole so that it would interact well with the glutamate residue. This may not be the case. An alternative explanation for the loss of potency is that the 2-aminothiazole ring is much smaller than 2-amino-4
Graphical Abstract
Figure 1: Lead compounds 1 and 2; 2- and 4-aminothiazole analogs 3 and 4a-c.
Figure 2: A: The docking conformation of 3 in the active site of rat nNOS; B: The docking conformation of 4b ...
Scheme 1: Attempts to open epoxide 5 with deprotonated aminothiazoles. i) n-BuLi, 2 equiv, THF, −78 °C; ii) 5...
Scheme 2: Assembly of 2-aminothiazole fragment. i) AllylMgBr, ether, 0 °C, 15 min.; ii) TBSCl, imidazole, DMF...
Scheme 3: Synthesis of compound 3. i) 4-chlorobenzylchloride, EtOH, reflux, 4 h; ii) Boc2O, TEA, MeOH, 3 h; i...
Scheme 4: Assembly of the 4-aminothiazole fragments. i) LiCH2CN, THF, 0 °C, 4 h; ii) (NH4)2S (aq), MeOH, 16 h...
Scheme 5: Synthesis of inhibitor 4a-c. The 4-aminothiazoles were not stable in water undergoing tautomerizati...
Colchitaxel, a coupled compound made from microtubule inhibitors colchicine and paclitaxel
- Karunananda Bombuwala,
- Thomas Kinstle,
- Vladimir Popik,
- Sonal O. Uppal,
- James B. Olesen,
- Jose Viña and
- Carol A. Heckman
Beilstein J. Org. Chem. 2006, 2, No. 13, doi:10.1186/1860-5397-2-13
- for tubulin-binding activity, the acetamide linkage on ring B could be replaced by an amide containing a glutamate linker. Alteration of the C-7 site on paclitaxel similarly had little or no inhibitory effect on its biological activity. The linker was attached to this position. The coupled compound
- . Indeed, this may contribute to the difficulty of understanding the effects of the drug combination (see below). In the synthesis of colchitaxel, the acetamide on ring B was replaced by an amide containing a glutamate linker. If a site could be identified on paclitaxel, which had little or no effect on
Graphical Abstract
Scheme 1: Reagents and conditions for synthesis of N-glutaryl-deacetylcolchicine. The reagents used at each s...
Scheme 2: Reagents and conditions for protection of paclitaxel and coupling to N-glutaryl-deacetylcolchicine ...
Figure 1: Microtubule arrangement as visualized by immunofluorescence localization of β-tubulin. Cells were t...
Figure 2: Projections of a VRO showing + ends localized by antibody against EB1 in a control cell. Cell was t...
Figure 3: Projections of a VRO showing + ends localized by antibody against EB1 in colchitaxel-treated cell. ...
Figure 4: Microtubule arrangement as visualized by immunofluorescence localization of β-tubulin. Cells were t...
