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Search for "acetylcholinesterase inhibitor" in Full Text gives 4 result(s) in Beilstein Journal of Organic Chemistry.
On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets
- Renato L. Carvalho,
- Amanda S. de Miranda,
- Mateus P. Nunes,
- Roberto S. Gomes,
- Guilherme A. M. Jardim and
- Eufrânio N. da Silva Júnior
Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126
Graphical Abstract
Scheme 1: Schematic overview of transition metals studied in C–H activation processes.
Scheme 2: (A) Known biological activities related to benzimidazole-based compounds; (B and C) an example of a...
Scheme 3: (A) Known biological activities related to quinoline-based compounds; (B and C) an example of a sca...
Scheme 4: (A) Known biological activities related to sulfur-containing compounds; (B and C) an example of a s...
Scheme 5: (A) Known biological activities related to aminoindane derivatives; (B and C) an example of a scand...
Scheme 6: (A) Known biological activities related to norbornane derivatives; (B and C) an example of a scandi...
Scheme 7: (A) Known biological activities related to aniline derivatives; (B and C) an example of a titanium-...
Scheme 8: (A) Known biological activities related to cyclohexylamine derivatives; (B) an example of an intram...
Scheme 9: (A) Known biologically active benzophenone derivatives; (B and C) photocatalytic oxidation of benzy...
Scheme 10: (A) Known bioactive fluorine-containing compounds; (B and C) vanadium-mediated C(sp3)–H fluorinatio...
Scheme 11: (A) Known biologically active Lythraceae alkaloids; (B) synthesis of (±)-decinine (30).
Scheme 12: (A) Synthesis of (R)- and (S)-boehmeriasin (31); (B) synthesis of phenanthroindolizidines by vanadi...
Scheme 13: (A) Known bioactive BINOL derivatives; (B and C) vanadium-mediated oxidative coupling of 2-naphthol...
Scheme 14: (A) Known antiplasmodial imidazopyridazines; (B) practical synthesis of 41.
Scheme 15: (A) Gold-catalyzed drug-release mechanism using 2-alkynylbenzamides; (B and C) chromium-mediated al...
Scheme 16: (A) Examples of anti-inflammatory benzaldehyde derivatives; (B and C) chromium-mediated difunctiona...
Scheme 17: (A and B) Manganese-catalyzed chemoselective intramolecular C(sp3)–H amination; (C) late-stage modi...
Scheme 18: (A and B) Manganese-catalyzed C(sp3)–H amination; (C) late-stage modification of a leelamine deriva...
Scheme 19: (A) Known bioactive compounds containing substituted N-heterocycles; (B and C) manganese-catalyzed ...
Scheme 20: (A) Known indoles that present GPR40 full agonist activity; (B and C) manganese-catalyzed C–H alkyl...
Scheme 21: (A) Examples of known biaryl-containing drugs; (B and C) manganese-catalyzed C–H arylation through ...
Scheme 22: (A) Known zidovudine derivatives with potent anti-HIV properties; (B and C) manganese-catalyzed C–H...
Scheme 23: (A and B) Manganese-catalyzed C–H organic photo-electrosynthesis; (C) late-stage modification.
Scheme 24: (A) Example of a known antibacterial silylated dendrimer; (B and C) manganese-catalyzed C–H silylat...
Scheme 25: (A and B) Fe-based small molecule catalyst applied for selective aliphatic C–H oxidations; (C) late...
Scheme 26: (A) Examples of naturally occurring gracilioethers; (B) the first total synthesis of gracilioether ...
Scheme 27: (A and B) Selective aliphatic C–H oxidation of amino acids; (C) late-stage modification of proline-...
Scheme 28: (A) Examples of Illicium sesquiterpenes; (B) first chemical synthesis of (+)-pseudoanisatin (80) in...
Scheme 29: (A and B) Fe-catalyzed deuteration; (C) late-stage modification of pharmaceuticals.
Scheme 30: (A and B) Biomimetic Fe-catalyzed aerobic oxidation of methylarenes to benzaldehydes (PMHS, polymet...
Scheme 31: (A) Known tetrahydroquinolines with potential biological activities; (B and C) redox-selective Fe c...
Scheme 32: (A) Known drugs containing a benzofuran unit; (B and C) Fe/Cu-catalyzed tandem O-arylation to acces...
Scheme 33: (A) Known azaindolines that act as M4 muscarinic acetylcholine receptor agonists; (B and C) intramo...
Scheme 34: (A) Known indolinones with anticholinesterase activity; (B and C) oxidative C(sp3)–H cross coupling...
Scheme 35: (A and B) Cobalt-catalyzed C–H alkenylation of C-3-peptide-containing indoles; (C) derivatization b...
Scheme 36: (A) Cobalt-Cp*-catalyzed C–H methylation of known drugs; (B and C) scope of the o-methylated deriva...
Scheme 37: (A) Known lasalocid A analogues; (B and C) three-component cobalt-catalyzed C–H bond addition; (D) ...
Scheme 38: (A and B) Cobalt-catalyzed C(sp2)–H amidation of thiostrepton.
Scheme 39: (A) Known 4H-benzo[d][1,3]oxazin-4-one derivatives with hypolipidemic activity; (B and C) cobalt-ca...
Scheme 40: (A and B) Cobalt-catalyzed C–H arylation of pyrrole derivatives; (C) application for the synthesis ...
Scheme 41: (A) Known 2-phenoxypyridine derivatives with potent herbicidal activity; (B and C) cobalt-catalyzed...
Scheme 42: (A) Natural cinnamic acid derivatives; (B and C) cobalt-catalyzed C–H carboxylation of terminal alk...
Scheme 43: (A and B) Cobalt-catalyzed C–H borylation; (C) application to the synthesis of flurbiprofen.
Scheme 44: (A) Benzothiazoles known to present anticonvulsant activities; (B and C) cobalt/ruthenium-catalyzed...
Scheme 45: (A and B) Cobalt-catalyzed oxygenation of methylene groups towards ketone synthesis; (C) synthesis ...
Scheme 46: (A) Known anticancer tetralone derivatives; (B and C) cobalt-catalyzed C–H difluoroalkylation of ar...
Scheme 47: (A and B) Cobalt-catalyzed C–H thiolation; (C) application in the synthesis of quetiapine (153).
Scheme 48: (A) Known benzoxazole derivatives with anticancer, antifungal, and antibacterial activities; (B and...
Scheme 49: (A and B) Cobalt-catalyzed C–H carbonylation of naphthylamides; (C) BET inhibitors 158 and 159 tota...
Scheme 50: (A) Known bioactive pyrrolo[1,2-a]quinoxalin-4(5H)-one derivatives; (B and C) cobalt-catalyzed C–H ...
Scheme 51: (A) Known antibacterial cyclic sulfonamides; (B and C) cobalt-catalyzed C–H amination of propargyli...
Scheme 52: (A and B) Cobalt-catalyzed intramolecular 1,5-C(sp3)–H amination; (C) late-stage functionalization ...
Scheme 53: (A and B) Cobalt-catalyzed C–H/C–H cross-coupling between benzamides and oximes; (C) late-state syn...
Scheme 54: (A) Known anticancer natural isoquinoline derivatives; (B and C) cobalt-catalyzed C(sp2)–H annulati...
Scheme 55: (A) Enantioselective intramolecular nickel-catalyzed C–H activation; (B) bioactive obtained motifs;...
Scheme 56: (A and B) Nickel-catalyzed α-C(sp3)–H arylation of ketones; (C) application of the method using kno...
Scheme 57: (A and B) Nickel-catalyzed C(sp3)–H acylation of pyrrolidine derivatives; (C) exploring the use of ...
Scheme 58: (A) Nickel-catalyzed C(sp3)–H arylation of dioxolane; (B) library of products obtained from biologi...
Scheme 59: (A) Intramolecular enantioselective nickel-catalyzed C–H cycloalkylation; (B) product examples, inc...
Scheme 60: (A and B) Nickel-catalyzed C–H deoxy-arylation of azole derivatives; (C) late-stage functionalizati...
Scheme 61: (A and B) Nickel-catalyzed decarbonylative C–H arylation of azole derivatives; (C) application of t...
Scheme 62: (A and B) Another important example of nickel-catalyzed C–H arylation of azole derivatives; (C) app...
Scheme 63: (A and B) Another notable example of a nickel-catalyzed C–H arylation of azole derivatives; (C) lat...
Scheme 64: (A and B) Nickel-based metalorganic framework (MOF-74-Ni)-catalyzed C–H arylation of azole derivati...
Scheme 65: (A) Known commercially available benzothiophene-based drugs; (B and C) nickel-catalyzed C–H arylati...
Scheme 66: (A) Known natural tetrahydrofuran-containing substances; (B and C) nickel-catalyzed photoredox C(sp3...
Scheme 67: (A and B) Another notable example of a nickel-catalyzed photoredox C(sp3)–H alkylation/arylation; (...
Scheme 68: (A) Electrochemical/nickel-catalyzed C–H alkoxylation; (B) achieved scope, including three using na...
Scheme 69: (A) Enantioselective photoredox/nickel catalyzed C(sp3)–H arylation; (B) achieved scope, including ...
Scheme 70: (A) Known commercially available trifluoromethylated drugs; (B and C) nickel-catalyzed C–H trifluor...
Scheme 71: (A and B) Stereoselective nickel-catalyzed C–H difluoroalkylation; (C) late-stage functionalization...
Scheme 72: (A) Cu-mediated ortho-amination of oxalamides; (B) achieved scope, including derivatives obtained f...
Scheme 73: (A) Electro-oxidative copper-mediated amination of 8-aminoquinoline-derived amides; (B) achieved sc...
Scheme 74: (A and B) Cu(I)-mediated C–H amination with oximes; (C) derivatization using telmisartan (241) as s...
Scheme 75: (A and B) Cu-mediated amination of aryl amides using ammonia; (C) late-stage modification of proben...
Scheme 76: (A and B) Synthesis of purine nucleoside analogues using copper-mediated C(sp2)–H activation.
Scheme 77: (A) Copper-mediated annulation of acrylamide; (B) achieved scope, including the synthesis of the co...
Scheme 78: (A) Known bioactive compounds containing a naphthyl aryl ether motif; (B and C) copper-mediated eth...
Scheme 79: (A and B) Cu-mediated alkylation of N-oxide-heteroarenes; (C) late-stage modification.
Scheme 80: (A) Cu-mediated cross-dehydrogenative coupling of polyfluoroarenes and alkanes; (B) scope from know...
Scheme 81: (A) Known anticancer acrylonitrile compounds; (B and C) Copper-mediated cyanation of unactivated al...
Scheme 82: (A) Cu-mediated radiofluorination of 8-aminoquinoline-derived aryl amides; (B) achieved scope, incl...
Scheme 83: (A) Examples of natural β-carbolines; (B and C) an example of a zinc-catalyzed C–H functionalizatio...
Scheme 84: (A) Examples of anticancer α-aminophosphonic acid derivatives; (B and C) an example of a zinc-catal...
Synthesis of 3-aminocoumarin-N-benzylpyridinium conjugates with nanomolar inhibitory activity against acetylcholinesterase
- Nisachon Khunnawutmanotham,
- Cherdchai Laongthipparos,
- Patchreenart Saparpakorn,
- Nitirat Chimnoi and
- Supanna Techasakul
Beilstein J. Org. Chem. 2018, 14, 2545–2552, doi:10.3762/bjoc.14.231
- target enzyme by a dual binding site mechanism whereby the coumarin portion binds with the peripheral anionic site while the N-benzylpyridinium residue binds with the catalytic anionic site of the enzyme. Keywords: acetylcholinesterase inhibitor; 3-aminocoumarin; N-benzylpyridinium; dual binding site
Graphical Abstract
Figure 1: Design of the target compounds.
Scheme 1: Synthesis of 3-aminocoumarin-N-benzylpyridinium salts.
Figure 2: Docked conformations of donepezil (ball-and-stick model; pink), compounds 9a, 9b, 9e, 9h, and 9i (s...
Figure 3: Binding interactions in the rhAChE binding pocket with (a) 4a, (b) 9a, (c) 9b, (d) 9e, (e) 9h, (f) ...
Synthesis of 1-indanones with a broad range of biological activity
- Marika Turek,
- Dorota Szczęsna,
- Marek Koprowski and
- Piotr Bałczewski
Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48
- -indanone derivatives 66 were obtained in 13–86% yields (Scheme 22). This method was further applied to the synthesis of biologically active compounds, such as 1-tetralones, 1-benzosuberones and donepezil (a potent acetylcholinesterase inhibitor used in the treatment of Alzheimer’s disease). Halo-1
Graphical Abstract
Figure 1: Biologically active 1-indanones and their structural analogues.
Figure 2: Number of papers about (a) 1-indanones, (b) synthesis of 1-indanones.
Scheme 1: Synthesis of 1-indanone (2) from hydrocinnamic acid (1).
Scheme 2: Synthesis of 1-indanone (2) from 3-(2-bromophenyl)propionic acid (3).
Scheme 3: Synthesis of 1-indanones 5 from 3-arylpropionic acids 4.
Scheme 4: Synthesis of kinamycin (9a) and methylkinamycin C (9b).
Scheme 5: Synthesis of trifluoromethyl-substituted arylpropionic acids 12, 1-indanones 13 and dihydrocoumarin...
Scheme 6: Synthesis of 1-indanones 16 from benzoic acids 15.
Scheme 7: Synthesis of 1-indanones 18 from arylpropionic and 3-arylacrylic acids 17.
Scheme 8: The NbCl5-induced one-step synthesis of 1-indanones 22.
Scheme 9: Synthesis of biologically active 1-indanone derivatives 26.
Scheme 10: Synthesis of enantiomerically pure indatraline ((−)-29).
Scheme 11: Synthesis of 1-indanone (2) from the acyl chloride 30.
Scheme 12: Synthesis of the mechanism-based inhibitors 33 of coelenterazine.
Scheme 13: Synthesis of the indane 2-imidazole derivative 37.
Scheme 14: Synthesis of fluorinated PAHs 41.
Scheme 15: Synthesis of 1-indanones 43 via transition metal complexes-catalyzed carbonylative cyclization of m...
Scheme 16: Synthesis of 6-methyl-1-indanone (46).
Scheme 17: Synthesis of 1-indanone (2) from ester 48.
Scheme 18: Synthesis of benzopyronaphthoquinone 51 from the spiro-1-indanone 50.
Scheme 19: Synthesis of the selective endothelin A receptor antagonist 55.
Scheme 20: Synthesis of 1-indanones 60 from methyl vinyl ketone (57).
Scheme 21: Synthesis of 1-indanones 64 from diethyl phthalate 61.
Scheme 22: Synthesis of 1-indanone derivatives 66 from various Meldrum’s acids 65.
Scheme 23: Synthesis of halo 1-indanones 69.
Scheme 24: Synthesis of substituted 1-indanones 71.
Scheme 25: Synthesis of spiro- and fused 1-indanones 73 and 74.
Scheme 26: Synthesis of spiro-1,3-indanodiones 77.
Scheme 27: Mechanistic pathway for the NHC-catalyzed Stetter–Aldol–Michael reaction.
Scheme 28: Synthesis of 2-benzylidene-1-indanone derivatives 88a–d.
Scheme 29: Synthesis of 1-indanone derivatives 90a–i.
Scheme 30: Synthesis of 1-indanones 96 from o-bromobenzaldehydes 93 and alkynes 94.
Scheme 31: Synthesis of 3-hydroxy-1-indanones 99.
Scheme 32: Photochemical preparation of 1-indanones 103 from ketones 100.
Scheme 33: Synthesis of chiral 3-aryl-1-indanones 107.
Scheme 34: Photochemical isomerization of 2-methylbenzil 108.
Scheme 35: Synthesis of 2-hydroxy-1-indanones 111a–c.
Scheme 36: Synthesis of 1-indanone derivatives 113 and 114 from η6-1,2-dioxobenzocyclobutene complex 112.
Scheme 37: Synthesis of nakiterpiosin (117).
Scheme 38: Synthesis of 2-alkyl-1-indanones 120.
Scheme 39: Synthesis of fluorine-containing 1-indanone derivatives 123.
Scheme 40: Synthesis of 2-benzylidene and 2-benzyl-1-indanones 126, 127 from the chalcone 124.
Scheme 41: Synthesis of 2-bromo-6-methoxy-3-phenyl-1-indanone (130).
Scheme 42: Synthesis of combretastatin A-4-like indanones 132a–s.
Figure 3: Chemical structures of investigated dienones 133 and synthesized cyclic products 134–137.
Figure 4: Chemical structures of 1-indanones and their heteroatom analogues 138–142.
Scheme 43: Synthesis of 2-phosphorylated and 2-non-phosphorylated 1-indanones 147 and 148 from β-ketophosphona...
Scheme 44: Photochemical synthesis of 1-indanone derivatives 150, 153a, 153b.
Scheme 45: Synthesis of polysubstituted-1-indanones 155, 157.
Scheme 46: Synthesis of 1-indanones 159a–g from α-arylpropargyl alcohols 158 using RhCl(PPh3)3 as a catalyst.
Scheme 47: Synthesis of optically active 1-indanones 162 via the asymmetric Rh-catalyzed isomerization of race...
Scheme 48: Mechanism of the Rh-catalyzed isomerization of α-arylpropargyl alcohols 161 to 1-indanones 162.
Figure 5: Chemical structure of abicoviromycin (168) and its new benzo derivative 169.
Scheme 49: Synthesis of racemic benzoabicoviromycin 172.
Scheme 50: Synthesis of [14C]indene 176.
Scheme 51: Synthesis of indanone derivatives 178–180.
Scheme 52: Synthesis of racemic pterosin A 186.
Scheme 53: Synthesis of trans-2,3-disubstituted 1-indanones 189.
Scheme 54: Synthesis of 3-aryl-1-indanone derivatives 192.
Scheme 55: Synthesis of 1-indanone derivatives 194 from 3-(2-iodoaryl)propanonitriles 193.
Scheme 56: Synthesis of 1-indanones 200–204 by cyclization of aromatic nitriles.
Scheme 57: Synthesis of 1,1’-spirobi[indan-3,3’-dione] derivative 208.
Scheme 58: Total synthesis of atipamezole analogues 211.
Scheme 59: Synthesis of 3-[4-(1-piperidinoethoxy)phenyl]spiro[indene-1,1’-indan]-5,5’-diol hydrochloride 216.
Scheme 60: Synthesis of 3-arylindan-1-ones 219.
Scheme 61: Synthesis of 2-hydroxy-1-indanones 222.
Scheme 62: Synthesis of the 1-indanone 224 from the THP/MOM protected chalcone epoxide 223.
Scheme 63: Synthesis of 1-indanones 227 from γ,δ-epoxy ketones 226.
Scheme 64: Synthesis of 2-hydroxy-2-methylindanone (230).
Scheme 65: Synthesis of 1-indanone derivatives 234 from cyclopropanol derivatives 233.
Scheme 66: Synthesis of substituted 1-indanone derivatives 237.
Scheme 67: Synthesis of 7-methyl substituted 1-indanone 241 from 1,3-pentadiene (238) and 2-cyclopentenone (239...
Scheme 68: Synthesis of disubstituted 1-indanone 246 from the siloxydiene 244 and 2-cyclopentenone 239.
Scheme 69: Synthesis of 5-hydroxy-1-indanone (250) via the Diels–Alder reaction of 1,3-diene 248 with sulfoxid...
Scheme 70: Synthesis of halogenated 1-indanones 253a and 253b.
Scheme 71: Synthesis of 1-indanones 257 and 258 from 2-bromocyclopentenones 254.
Scheme 72: Synthesis of 1-indanone 261 from 2-bromo-4-acetoxy-2-cyclopenten-1-one (260) and 1,2-dihydro-4-viny...
Scheme 73: Synthesis of 1-indanone 265 from 1,2-dihydro-7-methoxy-4-vinylnaphthalene (262) and bromo-substitut...
Scheme 74: Synthesis of 1-indanone 268 from dihydro-3-vinylphenanthrene 266 and 4-acetoxy-2-cyclopenten-1-one (...
Scheme 75: Synthesis of 1-indanone 271 from phenylselenyl-substituted cyclopentenone 268.
Scheme 76: Synthesis of 1-indanone 272 from the trienone 270.
Scheme 77: Synthesis of the 1-indanone 276 from the aldehyde 273.
Scheme 78: Synthesis of 1-indanones 278 and 279.
Scheme 79: Synthesis of 1-indanone 285 from octa-1,7-diyne (282) and cyclopentenone 239.
Scheme 80: Synthesis of benz[f]indan-1-one (287) from cyclopentenone 239 and o-bis(dibromomethyl)benzene (286)....
Scheme 81: Synthesis of 3-methyl-substituted benz[f]indan-1-one 291 from o-bis(dibromomethyl)benzene (286) and...
Scheme 82: Synthesis of benz[f]indan-1-one (295) from the anthracene epidioxide 292.
Scheme 83: Synthesis of 1-indanone 299 from homophthalic anhydride 298 and cyclopentynone 297.
Scheme 84: Synthesis of cyano-substituted 1-indanone derivative 301 from 2-cyanomethylbenzaldehyde (300) and c...
Scheme 85: Synthesis of 1-indanone derivatives 303–305 from ketene dithioacetals 302.
Scheme 86: Synthesis of 1-indanones 309–316.
Scheme 87: Mechanism of the hexadehydro-Diels–Alder (HDDA) reaction.
Scheme 88: Synthesis of 1-indenone 318 and 1-indanones 320 and 321 from tetraynes 317 and 319.
Scheme 89: Synthesis of 1-indanone 320 from the triyn 319.
Scheme 90: Synthesis 1-indanone 328 from 2-methylfuran 324.
Scheme 91: Synthesis of 1-indanones 330 and 331 from furans 329.
Scheme 92: Synthesis of 1-indanone 333 from the cycloadduct 332.
Scheme 93: Synthesis of (S)-3-arylindan-1-ones 335.
Scheme 94: Synthesis of (R)-2-acetoxy-1-indanone 338.
Figure 6: Chemical structures of obtained cyclopenta[α]phenanthrenes 339.
Scheme 95: Synthesis of the benzoindanone 343 from arylacetaldehyde 340 with 1-trimethylsilyloxycyclopentene (...
Unconventional application of the Mitsunobu reaction: Selective flavonolignan dehydration yielding hydnocarpins
- Guozheng Huang,
- Simon Schramm,
- Jörg Heilmann,
- David Biedermann,
- Vladimír Křen and
- Michael Decker
Beilstein J. Org. Chem. 2016, 12, 662–669, doi:10.3762/bjoc.12.66
- , our group has developed a hybrid drug combining silibinin with tacrine (a potent acetylcholinesterase inhibitor for treatment of Alzheimer’s disease), which shows neuro- and hepatoprotective effects exceeding the cytoprotective effects of silibinin and effectively counteracts tacrine’s dose-dependent
Graphical Abstract
Figure 1: Structures of silibinin, isosilybin, and silychristin, and hydnocarpin-type flavonolignans.
Figure 2: Synthetic strategy of semi-synthesis of hydnocarpins from silybins [22].
Scheme 1: Synthesis of ester derivatives of silibinin and conversion to hydnocarpin-type compounds. Reaction ...
Figure 3: Putative mechanism of dehydration of flavanonols under Mitsunobu conditions.
Scheme 2: Attempt to dehydrate catechin. Reagents and conditions: a) p-nitrobenzoic acid, Ph3P, DIAD, THF, rt...
Scheme 3: Preparation of hydnocarpin (4) and isohydnocarpin (6) and attempt to dehydrate silydianin A (11). R...
