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Search for "antimalarial activity" in Full Text gives 21 result(s) in Beilstein Journal of Organic Chemistry.
Synthesis and characterisation of new antimalarial fluorinated triazolopyrazine compounds
- Kah Yean Lum,
- Jonathan M. White,
- Daniel J. G. Johnson,
- Vicky M. Avery and
- Rohan A. Davis
Beilstein J. Org. Chem. 2023, 19, 107–114, doi:10.3762/bjoc.19.11
- and Dd2 strains) and the cytotoxicity against a human embryonic kidney (HEK293) cell line were tested. Some of the compounds demonstrated moderate antimalarial activity with IC50 values ranging from 0.2 to >80 µM; none of the compounds displayed any cytotoxicity against HEK293 cells at 80 µM
- . Antimalarial activity was significantly reduced when C-8 of the triazolopyrazine scaffold was substituted with CF3 and CF2H moieties, whereas incorporation of a CF2Me group at the same position completely abolished antiplasmodial effects. Keywords: antimalarial; characterisation; DiversinateTM; fluorine
- triazolopyrazines were all evaluated in vitro for antimalarial activity and cytotoxicity. Results and Discussion Previous structure–activity relationship (SAR) studies reported that any substitution at the C8 position of Series 4 triazolopyrazines can lower the potency for P. falciparum [14][15][16]. However, a
Graphical Abstract
Scheme 1: Synthesis of ether triazolopyrazine derivatives 4–9.
Scheme 2: Synthesis of fluorinated triazolopyrazine compounds (10–18) via Diversinate™ chemistry.
Figure 1: Key HMBC, COSY and ROESY correlations, and ORTEP drawing of 18.
Synthetic study toward the diterpenoid aberrarone
- Liang Shi,
- Zhiyu Gao,
- Yiqing Li,
- Yuanhao Dai,
- Yu Liu,
- Lili Shi and
- Hong-Dong Hao
Beilstein J. Org. Chem. 2022, 18, 1625–1628, doi:10.3762/bjoc.18.173
- antitumor, antituberculosis and antimalarial activities [2][3][4][5][6]. Among these structurally intriguing natural products, aberrarone (1) shows antimalarial activity against the chloroquine-resistant strain of Plasmodium falciparum (IC50 = 10 μg/mL) [7]. Structurally, aberrarone possesses an unusual
Graphical Abstract
Figure 1: Selected representative natural products with 6-5-5 tricyclic skeleton.
Scheme 1: Retrosynthetic analysis of aberrarone (1).
Scheme 2: Synthetic study toward aberrarone (1).
Experimental and theoretical studies on the synthesis of 1,4,5-trisubstituted pyrrolidine-2,3-diones
- Nguyen Tran Nguyen,
- Vo Viet Dai,
- Nguyen Ngoc Tri,
- Luc Van Meervelt,
- Nguyen Tien Trung and
- Wim Dehaen
Beilstein J. Org. Chem. 2022, 18, 1140–1153, doi:10.3762/bjoc.18.118
- ][10]. In addition, these 2-oxopyrroles are structural subunits of various bioactive natural compounds and synthetic drugs. For example, codinaeopsin has been isolated from a fungal extract of a tree called Vochysia guatemalensis which shows antimalarial activity [11]. Pyrrocidine A was isolated from
Graphical Abstract
Figure 1: Structure of naturally occurring and synthetic 2-pyrrolidone derivatives.
Figure 2: Structure of natural compounds containing a 1,5-dihydro-2H-pyrrol-2-one subunit.
Scheme 1: Synthesis of substituted 4-acetyl-3-hydroxy-3-pyrroline-2-ones 4 via three-component reaction.
Scheme 2: Proposed mechanistic path for the synthesis of substituted 4-acetyl-3-hydroxy-3-pyrroline-2-ones.
Scheme 3: Tautomerism of compounds 4a–c in DMSO.
Figure 3: View of the molecular structure of compound 10aa with atom labeling. Displacement ellipsoids are dr...
Figure 4: The PES of reaction for the synthesis of 1,4,5-trisubstituted pyrrolidine-2,3-dione 10ab enamine de...
Scheme 4: Reaction pathways from 4a, 4a’ to 10ab via IS5 in the gase phase.
Scheme 5: Reaction pathways from 4a to 10ab-v2 via IS3 in the gase phase.
Figure 5: The PES for the possible pathways (1), (2), (3), and (4) in ethanol solvent.
Figure 6: The optimized structures of some reactants, intermediates, transition states, and products in the p...
Structural basis for endoperoxide-forming oxygenases
- Takahiro Mori and
- Ikuro Abe
Beilstein J. Org. Chem. 2022, 18, 707–721, doi:10.3762/bjoc.18.71
- , natural and (semi)synthetic endoperoxides with wide structural diversity show antimalarial activity against Plasmodium falciparum malaria. In this case, the reductive activation of the endoperoxide ring with the homolytic cleavage of the O–O bond leads to the generation of carbon-centered free radicals
- that play important roles in antimalarial activity by damaging membranes, inhibiting nucleic acid and protein syntheses, and so on [8][9]. The best studied endoperoxide-containing compound is probably prostaglandin H2 (PGH2), the common precursor of biologically active prostanoids [10][11][12
Graphical Abstract
Figure 1: Examples of endoperoxide-containing natural products.
Scheme 1: Reactions of COXs.
Figure 2: Structures of COXs [52,53]. (A) The overall structure of ovine COX-1. (B and C) Comparison of the cyclooxy...
Scheme 2: Proposed reaction mechanisms of COXs [24].
Scheme 3: General reaction mechanism of Fe/2OG oxygenases.
Scheme 4: Reaction of FtmOx1 [68-71].
Figure 3: Structure of FtmOx1 [71]. (A) The FtmOx1 binary structure in complex with 2OG. (B and C) Comparison of ...
Scheme 5: Proposed COX-like mechanism of FtmOx1 [68].
Scheme 6: Proposed CarC-like mechanism of FtmOx1 [70].
Scheme 7: Reaction of NvfI [28].
Scheme 8: Possible reaction pathways leading to fumigatonoid A [28].
Figure 4: Structure of NvfI [28]. (A–C) Conformational changes of loop regions: (A) open conformation, (B) partia...
Scheme 9: Another possible reaction pathway for the formation of fumigatonoid A [28].
Chemistry of polyhalogenated nitrobutadienes, 17: Efficient synthesis of persubstituted chloroquinolinyl-1H-pyrazoles and evaluation of their antimalarial, anti-SARS-CoV-2, antibacterial, and cytotoxic activities
- Viktor A. Zapol’skii,
- Isabell Berneburg,
- Ursula Bilitewski,
- Melissa Dillenberger,
- Katja Becker,
- Stefan Jungwirth,
- Aditya Shekhar,
- Bastian Krueger and
- Dieter E. Kaufmann
Beilstein J. Org. Chem. 2022, 18, 524–532, doi:10.3762/bjoc.18.54
- cycle from 3-methyl-2-(2,3,3-trichloro-1-nitroallylidene)oxazolidine (6) is also described. In addition, the antimalarial activity of the synthesized compounds has been evaluated in vitro against the protozoan malaria parasite Plasmodium falciparum. Notably, the 7-chloro-4-(5-(dichloromethyl)-4-nitro-3
- ± 0.04 µM (100 ng/mL, 200 nM), respectively. Two compounds (3b and 10d) have also been tested for anti-SARS-CoV-2, antibacterial, and cytotoxic activity. Keywords: antimalarial activity; anti-SARS-CoV-2 activity; chloroquine; 2-nitroperchlorobutadiene; nucleophilic vinylic substitution; 1H-pyrazoles
- already been described in the literature [15][16][17][18]. The antimalarial activity of chloroquinolinyl-pyrazoles, synthesized from the reaction of 1,1,1-trifluoro-4-methoxy-3-alken-2-ones with 4-hydrazinyl-7-chloroquinoline, has been evaluated in vitro against a chloroquine-resistant Plasmodium
Graphical Abstract
Figure 1: The structures of chloroquine, hydroxychloroquine, and amodiaquine.
Scheme 1: Synthesis of 3-azolylpyrazoles 3a–c.
Scheme 2: Assumed mechanism for the formation of 1H-pyrazoles 3a–c.
Scheme 3: Synthesis of 3-aminopyrazoles 5b–k and 5-aminopyrazoles 5a and 5l–o.
Scheme 4: Orientation of nucleophilic attack of 7-chloro-4-hydrazinylquinoline on nitrobutadienes 4.
Scheme 5: Synthesis of oxazolidine 6 and pyrazole 7.
Scheme 6: A plausible mechanism for the formation of pyrazole 7.
Scheme 7: Synthesis of pyrazoles 9 and sulfoxide 10d.
Scheme 8: Synthesis of pyrazole 11.
First total synthesis of hoshinoamide A
- Haipin Zhou,
- Zihan Rui,
- Yiming Yang,
- Shengtao Xu,
- Yutian Shao and
- Long Liu
Beilstein J. Org. Chem. 2021, 17, 2924–2931, doi:10.3762/bjoc.17.201
- have a relatively simple structure and therefore make an attractive target for further medicinal chemistry studies. To enable these new SAR studies, we need to develop an efficient synthetic method to provide sufficient materials firstly. Hoshinoamide A shows a better antimalarial activity and less
- hoshinoamide A and other highly methylated polypeptide analogues. Our strategy was also helpful to further study its antimalarial activity. Structure-and-activity and functional studies with the fluorescent-labeled analogs are currently under investigation in our lab. Experimental General experimental
Graphical Abstract
Figure 1: a) Structures of hoshinoamides A and B. b) Structure of hoshinoamide C.
Scheme 1: Synthesis of resin-bound tripeptide 3 by SPPS. DIPEA: N,N-diisopropylethylamine; HCTU: O-(6-chloro-...
Scheme 2: Synthesis of dipeptide 6. HATU: 2-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorop...
Scheme 3: Synthesis of hoshinoamide A.
Synthetic accesses to biguanide compounds
- Oleksandr Grytsai,
- Cyril Ronco and
- Rachid Benhida
Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82
Graphical Abstract
Figure 1: Tautomeric forms of biguanide.
Figure 2: Illustrations of neutral, monoprotonated, and diprotonated structures biguanide.
Figure 3: The main approaches for the synthesis of biguanides. The core structure is obtained via the additio...
Scheme 1: The three main preparations of biguanides from cyanoguanidine.
Scheme 2: Synthesis of butylbiguanide using CuCl2 [16].
Scheme 3: Synthesis of biguanides by the direct fusion of cyanoguanidine and amine hydrochlorides [17,18].
Scheme 4: Synthesis of ethylbiguanide and phenylbiguanide as reported by Smolka and Friedreich [14].
Scheme 5: Synthesis of arylbiguanides through the reaction of cyanoguanidine with anilines in water [19].
Scheme 6: Synthesis of aryl- and alkylbiguanides by adaptations of Cohn’s procedure [20,21].
Scheme 7: Microwave-assisted synthesis of N1-aryl and -dialkylbiguanides [22,23].
Scheme 8: Synthesis of aryl- and alkylbiguanides by trimethylsilyl activation [24,26].
Scheme 9: Synthesis of phenformin analogs by TMSOTf activation [27].
Scheme 10: Synthesis of N1-(1,2,4-triazolyl)biguanides [28].
Scheme 11: Synthesis of 2-guanidinobenzazoles by addition of ortho-substituted anilines to cyanoguanidine [30,32] and...
Scheme 12: Synthesis of 2,4-diaminoquinazolines by the addition of 2-cyanoaniline to cyanoguanidine and from 3...
Scheme 13: Reactions of anthranilic acid and 2-mercaptobenzoic acid with cyanoguanidine [24,36,37].
Scheme 14: Synthesis of disubstituted biguanides with Cu(II) salts [38].
Scheme 15: Synthesis of an N1,N2,N5-trisubstituted biguanide by fusion of an amine hydrochloride and 2-cyano-1...
Scheme 16: Synthesis of N1,N5-disubstituted biguanides by the addition of anilines to cyanoguanidine derivativ...
Scheme 17: Microwave-assisted additions of piperazine and aniline hydrochloride to substituted cyanoguanidines ...
Scheme 18: Synthesis of N1,N5-alkyl-substituted biguanides by TMSOTf activation [27].
Scheme 19: Additions of oxoamines hydrochlorides to dimethylcyanoguanidine [49].
Scheme 20: Unexpected cyclization of pyridylcyanoguanidines under acidic conditions [50].
Scheme 21: Example of industrial synthesis of chlorhexidine [51].
Scheme 22: Synthesis of symmetrical N1,N5-diarylbiguanides from sodium dicyanamide [52,53].
Scheme 23: Synthesis of symmetrical N1,N5-dialkylbiguanides from sodium dicyanamide [54-56].
Scheme 24: Stepwise synthesis of unsymmetrical N1,N5-trisubstituted biguanides from sodium dicyanamide [57].
Scheme 25: Examples for the synthesis of unsymmetrical biguanides [58].
Scheme 26: Examples for the synthesis of an 1,3-diaminobenzoquinazoline derivative by the SEAr cyclization of ...
Scheme 27: Major isomers formed by the SEAr cyclization of symmetric biguanides derived from 2- and 3-aminophe...
Scheme 28: Lewis acid-catalyzed synthesis of 8H-pyrrolo[3,2-g]quinazoline-2,4-diamine [63].
Scheme 29: Synthesis of [1,2,4]oxadiazoles by the addition of hydroxylamine to dicyanamide [49,64].
Scheme 30: Principle of “bisamidine transfer” and analogy between the reactions with N-amidinopyrazole and N-a...
Scheme 31: Representative syntheses of N-amidino-amidinopyrazole hydrochloride [68,69].
Scheme 32: First examples of biguanide syntheses using N-amidino-amidinopyrazole [66].
Scheme 33: Example of “biguanidylation” of a hydrazide substrate [70].
Scheme 34: Example for the synthesis of biguanides using S-methylguanylisothiouronium iodide as “bisamidine tr...
Scheme 35: Synthesis of N-substituted N1-cyano-S-methylisothiourea precursors.
Scheme 36: Addition routes on N1-cyano-S-methylisothioureas.
Scheme 37: Synthesis of an hydroxybiguanidine from N1-cyano-S-methylisothiourea [77].
Scheme 38: Synthesis of an N1,N2,N3,N4,N5-pentaarylbiguanide from the corresponding triarylguanidine and carbo...
Scheme 39: Reactions of N,N,N’,N’-tetramethylguanidine (TMG) with carbodiimides to synthesize hexasubstituted ...
Scheme 40: Microwave-assisted addition of N,N,N’,N’-tetramethylguanidine to carbodiimides [80].
Scheme 41: Synthesis of N1-aryl heptasubstituted biguanides via a one-pot biguanide formation–copper-catalyzed ...
Scheme 42: Formation of 1,2-dihydro-1,3,5-triazine derivatives by the reaction of guanidine with excess carbod...
Scheme 43: Plausible mechanism for the spontaneous cyclization of triguanides [82].
Scheme 44: a) Formation of mono- and disubstituted (iso)melamine derivatives by the reaction of biguanides and...
Scheme 45: Reactions of 2-aminopyrimidine with carbodiimides to synthesize 2-guanidinopyrimidines as “biguanid...
Scheme 46: Non-catalyzed alternatives for the addition of 2-aminopyrimidine derivatives to carbodiimides. A) h...
Scheme 47: Addition of guanidinomagnesium halides to substituted cyanamides [90].
Scheme 48: Microwave-assisted synthesis of [11C]metformin by the reaction of 11C-labelled dimethylcyanamide an...
Scheme 49: Formation of 4-amino-6-dimethylamino[1,3,5]triazin-2-ol through the reaction of Boc-guanidine and d...
Scheme 50: Formation of 1,3,5-triazine derivatives via the addition of guanidines to substituted cyanamides [92].
Scheme 51: Synthesis of biguanide by the reaction of O-alkylisourea and guanidine [93].
Scheme 52: Aromatic nucleophilic substitution of guanidine on 2-O-ethyl-1,3,5-triazine [95].
Scheme 53: Synthesis of N1,N2-disubstituted biguanides by the reaction of guanidine and thioureas in the prese...
Scheme 54: Cyclization reactions involving condensations of guanidine(-like) structures with thioureas [97,98].
Scheme 55: Condensations of guanidine-like structures with thioureas [99,100].
Scheme 56: Condensations of guanidines with S-methylisothioureas [101,102].
Scheme 57: Addition of 2-amino-1,3-diazaaromatics to S-alkylisothioureas [103,104].
Scheme 58: Addition of guanidines to 2-(methylsulfonyl)pyrimidines [105].
Scheme 59: An example of a cyclodesulfurization reaction to a fused 3,5-diamino-1,2,4-triazole [106].
Scheme 60: Ring-opening reactions of 1,3-diaryl-2,4-bis(arylimino)-1,3-diazetidines [107].
Scheme 61: Formation of 3,5-diamino-1,2,4-triazole derivatives via addition of hydrazines to 1,3-diazetidine-2...
Scheme 62: Formation of a biguanide via the addition of aniline to 1,2,4-thiadiazol-3,5-diamines, ring opening...
Figure 4: Substitution pattern of biguanides accessible by synthetic pathways a–h.
Anthelmintic drug discovery: target identification, screening methods and the role of open science
- Frederick A. Partridge,
- Ruth Forman,
- Carole J. R. Bataille,
- Graham M. Wynne,
- Marina Nick,
- Angela J. Russell,
- Kathryn J. Else and
- David B. Sattelle
Beilstein J. Org. Chem. 2020, 16, 1203–1224, doi:10.3762/bjoc.16.105
- to radically open up the drug development process, with the goal of increasing the efficiency, reducing the cost of research duplication, reducing the hoarding of data and creating collaborative communities [174]. This approach has been applied to the discovery of compounds with antimalarial activity
Graphical Abstract
Figure 1: Structures of some current front-line anthelmintics discussed in this review. *Denotes the stereoge...
Figure 2: Structures of new anthelmintics drugs developed through repurposing, and new drugs or drug candidat...
Figure 3: Compounds with anthelmintic activity identified by a combination of screening against Ancylostoma c...
Figure 4: Inhibitors of S. mansoni thioredoxin glutathione reductase with anthelmintic activity [140].
Figure 5: Active compounds from anthelmintic screens using the MMV Pathogen Box. NTS: newly transformed schis...
Figure 6: Two resolution approaches to enantiopure PZQ (R)-5 discovered through A) open science and B) contra...
Combining the Ugi-azide multicomponent reaction and rhodium(III)-catalyzed annulation for the synthesis of tetrazole-isoquinolone/pyridone hybrids
- Gerardo M. Ojeda,
- Prabhat Ranjan,
- Pavel Fedoseev,
- Lisandra Amable,
- Upendra K. Sharma,
- Daniel G. Rivera and
- Erik V. Van der Eycken
Beilstein J. Org. Chem. 2019, 15, 2447–2457, doi:10.3762/bjoc.15.237
- variety of pharmacological and antimicrobial properties [5][6], including analgesic, antihypertensive, anti-inflammatory, anticancer, antifungal and antimalarial activity (Figure 1). A key feature of the tetrazole ring is its bioisosteric character with the carboxylic acid and amide functional groups
Graphical Abstract
Figure 1: Bioactive molecules containing a tetrazole, pyridone or isoquinolone ring.
Scheme 1: Approaches for the synthesis of tetrazoles and isoquinolones and their interplay as designed in thi...
Scheme 2: Scope of the Ugi-azide-4CR/deprotection/acylation sequence. Ugi-azide-4CR conducted at the 2.0 mmol...
Scheme 3: Influence of substituents R and R2 on the reaction outcome. For compounds 4k–m the overall yield in...
Scheme 4: Influence of the alkyne and R1 substituent on the reaction outcome.
Scheme 5: Scope of acrylic, heterocyclic and ring-fused N-acylaminomethyl tetrazole substrates.
Scheme 6: Proposed reaction mechanism using substrates 1a and 3a.
Doebner-type pyrazolopyridine carboxylic acids in an Ugi four-component reaction
- Maryna V. Murlykina,
- Oleksandr V. Kolomiets,
- Maryna M. Kornet,
- Yana I. Sakhno,
- Sergey M. Desenko,
- Victoriya V. Dyakonenko,
- Svetlana V. Shishkina,
- Oleksandr A. Brazhko,
- Vladimir I. Musatov,
- Alexander V. Tsygankov,
- Erik V. Van der Eycken and
- Valentyn A. Chebanov
Beilstein J. Org. Chem. 2019, 15, 1281–1288, doi:10.3762/bjoc.15.126
- discovery. The target products containing a heterocyclic core bound to a peptide-like chain also showed a broad spectrum of biological activity: β-secretase (BACE1) inhibitory activity [15]; inducing apoptosis in colorectal cancer cells [16]; antimalarial activity against a chloroquine (CQ) non-resistant
Graphical Abstract
Scheme 1: An overview of heterocyclic acids used in the Ugi reaction.
Scheme 2: Synthesis of pyrazolopyridine carboxylic acids 4 [45] and 7 [45] in Doebner-type reaction.
Figure 1: Molecular structure of N-(2-(tert-butylamino)-1-(4-chlorophenyl)-2-oxoethyl)-6-(4-methoxyphenyl)-3-...
Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams
- Edorta Martínez de Marigorta,
- Jesús M. de Los Santos,
- Ana M. Ochoa de Retana,
- Javier Vicario and
- Francisco Palacios
Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104
- , that shows antimalarial activity [40] and satavaptan, a selective V2-receptor antagonist that is useful for the treatment of cirrhosis (Figure 5) [41][42]. Additionally, methisazone is a 2-oxindole derivative that has been used as antiviral drug, especially for the prophylactic treatment of small-pox
Graphical Abstract
Figure 1: γ-Lactam-derived structures considered in this review.
Figure 2: Alkaloids containing an isoindolinone moiety.
Figure 3: Alkaloids containing the 2-oxindole ring system.
Figure 4: Drugs and biological active compounds containing an isoindolinone moiety.
Figure 5: Drugs and biologically active compounds bearing a 2-oxindole skeleton.
Scheme 1: Three-component reaction of benzoic acid 1, amides 2 and DMSO (3).
Scheme 2: Copper-catalysed three-component reaction of 2-iodobenzoic acids 10, alkynylcarboxylic acids 11 and...
Scheme 3: Proposed mechanism for the formation of methylene isoindolinones 13.
Scheme 4: Copper-catalysed three-component reaction of 2-iodobenzamide 17, terminal alkyne 18 and pyrrole or ...
Scheme 5: Palladium-catalysed three-component reaction of ethynylbenzamides 21, secondary amines 22 and CO (23...
Scheme 6: Proposed mechanism for the formation of methyleneisoindolinones 24.
Scheme 7: Copper-catalysed three-component reaction of formyl benzoate 29, amines 2 and alkynes 18.
Scheme 8: Copper-catalysed three-component reaction of formylbenzoate 29, amines 2 and ketones 31.
Scheme 9: Non-catalysed (A) and phase-transfer catalysed (B) three-component reactions of formylbenzoic acids ...
Scheme 10: Proposed mechanism for the formation of isoindolinones 36.
Scheme 11: Three-component reaction of formylbenzoic acid 33, amines 2 and fluorinated silyl ethers 39.
Scheme 12: Three-component Ugi reaction of 2-formylbenzoic acid (33), diamines 41 and isocyanides 42.
Scheme 13: Non-catalysed (A, B) and chiral phosphoric acid promoted (C) three-component Ugi reactions of formy...
Scheme 14: Proposed mechanism for the enantioselective formation of isoindolinones 46.
Scheme 15: Three-component reaction of benzoic acids 33 or 54, amines 2 and TMSCN (52).
Scheme 16: Several variations of the three-component reaction of formylbenzoic acids 33, amines 2 and isatoic ...
Scheme 17: Proposed mechanism for the synthesis of isoindoloquinazolinones 57.
Scheme 18: Three-component reaction of isobenzofuranone 61, amines 2 and isatoic anhydrides 56.
Scheme 19: Palladium-catalysed three-component reaction of 2-aminobenzamides 59, 2-bromobenzaldehydes 62 and C...
Scheme 20: Proposed mechanism for the palladium-catalysed synthesis of isoindoloquinazolinones 57.
Scheme 21: Four-component reaction of 2-vinylbenzoic acids 67, aryldioazonium tetrafluoroborates 68, DABCO·(SO2...
Scheme 22: Plausible mechanism for the formation of isoindolinones 71.
Scheme 23: Three-component reaction of trimethylsilylaryltriflates 77, isocyanides 42 and CO2 (78).
Scheme 24: Plausible mechanism for the three-component synthesis of phthalimides 79.
Scheme 25: Copper-catalysed three-component reaction of 2-formylbenzonitriles 85, arenes 86 and diaryliodonium...
Scheme 26: Copper-catalysed three-component reaction of 2-formylbenzonitriles 85, diaryliodonium salts 87 and ...
Scheme 27: Proposed mechanism for the formation of 2,3-diarylisoindolinones 88, 89 and 92.
Scheme 28: Palladium-catalysed three-component reaction of chloroquinolinecarbaldehydes 97 with isocyanides 42...
Scheme 29: Palladium-catalysed three-component reaction of imines 99 with CO (23) and ortho-iodoarylimines 100....
Scheme 30: Palladium-catalysed three-component reaction of amines 2 with CO (23) and aryl iodide 105.
Scheme 31: Three-component reaction of 2-ethynylanilines 109, perfluoroalkyl iodides 110 and carbon monoxide (...
Scheme 32: Ultraviolet-induced three-component reaction of N-(2-iodoaryl)acrylamides 113, DABCO·(SO2)2 (69) an...
Scheme 33: Proposed mechanism for the preparation of oxindoles 115.
Scheme 34: Three-component reaction of acrylamide 113, CO (23) and 1,4-benzodiazepine 121.
Scheme 35: Multicomponent reaction of sulfonylacrylamides 123, aryldiazonium tetrafluoroborates 68 and DABCO·(...
Scheme 36: Proposed mechanism for the preparation of oxindoles 124.
Scheme 37: Three-component reaction of N-arylpropiolamides 128, aryl iodides 129 and boronic acids 130.
Scheme 38: Proposed mechanism for the formation of diarylmethylene- and diarylallylideneoxindoles 131 and 132.
Scheme 39: Three-component reaction of cyclohexa-1,3-dione (136), amines 2 and alkyl acetylenedicarboxylates 1...
Scheme 40: Proposed mechanism for the formation of 2-oxindoles 138.
Synthesis and biological investigation of (+)-3-hydroxymethylartemisinin
- Toni Smeilus,
- Farnoush Mousavizadeh,
- Johannes Krieger,
- Xingzhao Tu,
- Marcel Kaiser and
- Athanassios Giannis
Beilstein J. Org. Chem. 2019, 15, 567–570, doi:10.3762/bjoc.15.51
- -hydroxymethyl-9-epi-artemisinin (18), starting from the known and readily available chiral aldehyde 3 and alkyne 4. Subsequently, the synthesized compounds have been evaluated for their antimalarial activity against the drug-sensitive P. falciparum NF54 strain. All of them were inactive. In addition, they did
- , whereas the desired (+)-3-hydroxymethylartemisinin (2) was produced from 17 in two steps including epimerization and cleavage of the TES group in excellent yield (Scheme 3). Finally, we evaluated the antimalarial activity of (+)-3-hydroxymethylartemisinin (2) as well as of the derivatives 16 and 18
Graphical Abstract
Figure 1: Structures of the natural (+)-artemisinin (1) and the synthesized (+)-3-hydroxymethylartemisinin (2...
Scheme 1: Synthesis of the Diels–Alder precursor 8 over four steps in 71% yield, starting from aldehyde 3 and...
Scheme 2: Synthesis of (+)-3-hydroxymethyl-9-desmethylartemisinin (16), starting from Diels–Alder derivatives ...
Scheme 3: Synthesis of (+)-3-hydroxymethyl-9-epi-artemisinin (18) and (+)-3-hydroxymethylartemisinin (2). Rea...
An overview of recent advances in duplex DNA recognition by small molecules
- Sayantan Bhaduri,
- Nihar Ranjan and
- Dev P. Arya
Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93
- . Suckling et al. designed a set of 31 Strathclyde minor groove binders (S-MGBs), derived from distamycin, by varying the head groups (amidine, amide, or alkene), heterocyclic building blocks and their alkyl substituents and the basicity of the C-terminal tail group in order to investigate their antimalarial
- activity against a chloroquine sensitive (3D7) and resistant (Dd2) strain of Plasmodium falciparum [100]. Conjugates with an alkene link between the two N-terminal building blocks and a C-alkylthiazole moiety appeared to the most active among others with IC50 values in the range of 30–500 nM. The same
Graphical Abstract
Figure 1: A figure showing the hydrogen bonding patterns observed in (a) duplex (b) triplex and (c) quadruple...
Figure 2: (a) Portions of MATα1–MATα2 are shown contacting the minor groove of the DNA substrate. Key arginin...
Figure 3: Chemical structures of naturally occurring and synthetic hybrid minor groove binders.
Figure 4: Synthetic structural analogs of distamycin A by replacing one or more pyrrole rings with other hete...
Figure 5: Pictorial representation of the binding model of pyrrole–imidazole (Py/Im) polyamides based on the ...
Figure 6: Chemical structures of synthetic “hairpin” pyrrole–imidazole (Py/Im) conjugates.
Figure 7: (a) Minor groove complex formation between DNA duplex and 8-ring cyclic Py/Im polyamide (conjugate ...
Figure 8: Telomere-targeting tandem hairpin Py/Im polyamides 23 and 24 capable of recognizing >10 base pairs; ...
Figure 9: Representative examples of recently developed DNA minor groove binders.
Figure 10: Chemical structures of bisbenzamidazoles Hoechst 33258 and 33342 and their synthetic structural ana...
Figure 11: Chemical structures of bisamidines such as diminazene, DAPI, pentamidine and their synthetic struct...
Figure 12: Representative examples of recently developed bisamidine derivatives.
Figure 13: Chemical structures of chromomycin, mithramycin and their synthetic structural analogs 91 and 92.
Figure 14: Chemical structures of well-known naturally occurring DNA binding intercalators.
Figure 15: Naturally occurring indolocarbazole rebeccamycin and its synthetic analogs.
Figure 16: Representative examples of naturally occurring and synthetic derivatives of DNA intercalating agent...
Figure 17: Several recent synthetic varieties of DNA intercalators.
Figure 18: Aminoglycoside (neomycin)–Hoechst 33258/intercalator conjugates.
Figure 19: Chemical structures of triazole linked neomycin dimers and neomycin–bisbenzimidazole conjugates.
Figure 20: Representative examples of naturally occurring and synthetic analogs of DNA binding alkylating agen...
Figure 21: Chemical structures of naturally occurring and synthetic analogs of pyrrolobenzodiazepines.
CF3SO2X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF3SO2Na
- Hélène Guyon,
- Hélène Chachignon and
- Dominique Cahard
Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272
- , it was essential to have a phenyl as a substituent in order to get good yields. A radical mechanism was proposed but the role of oxygen was not discussed. Aminoquinoline derivatives are found in naturally occurring and synthetic bioactive compounds, most notable for their antimalarial activity. So
Graphical Abstract
Scheme 1: Trifluoromethylation of enol acetates by Langlois.
Scheme 2: Trifluoromethylation of (het)aryl enol acetates.
Scheme 3: Mechanism for the trifluoromethylation of enol acetates.
Scheme 4: Oxidative trifluoromethylation of unactivated olefins and mechanistic pathway.
Scheme 5: Oxidative trifluoromethylation of acetylenic substrates.
Scheme 6: Metal free trifluoromethylation of styrenes.
Scheme 7: Synthesis of α-trifluoromethylated ketones by oxytrifluoromethylation of heteroatom-functionalised ...
Scheme 8: Catalysed photoredox trifluoromethylation of vinyl azides.
Scheme 9: Oxidative difunctionalisation of alkenyl MIDA boronates.
Scheme 10: Synthesis of β-trifluoromethyl ketones from cyclopropanols.
Scheme 11: Aryltrifluoromethylation of allylic alcohols.
Scheme 12: Cascade multicomponent synthesis of nitrogen heterocycles via azotrifluoromethylation of alkenes.
Scheme 13: Photocatalytic azotrifluoromethylation of alkenes with aryldiazonium salts and CF3SO2Na.
Scheme 14: Copper-promoted intramolecular aminotrifluoromethylation of alkenes with CF3SO2Na.
Scheme 15: Oxytrifluoromethylation of alkenes with CF3SO2Na and hydroxamic acid.
Scheme 16: Manganese-catalysed oxytrifluoromethylation of styrene derivatives.
Scheme 17: Oxytrifluoromethylation of alkenes with NMP/O2 and CF3SO2Na.
Scheme 18: Intramolecular oxytrifluoromethylation of alkenes.
Scheme 19: Hydrotrifluoromethylation of styrenyl alkenes and unactivated aliphatic alkenes.
Scheme 20: Hydrotrifluoromethylation of electron-deficient alkenes.
Scheme 21: Hydrotrifluoromethylation of alkenes by iridium photoredox catalysis.
Scheme 22: Iodo- and bromotrifluoromethylation of alkenes by CF3SO2Na/I2O5 or CF3SO2Na / NaBrO3.
Scheme 23: N-methyl-9-mesityl acridinium and visible-light-induced chloro-, bromo- and SCF3 trifluoromethylati...
Scheme 24: Carbotrifluoromethylation of N-arylacrylamides with CF3SO2Na / TBHP by Lipshutz.
Scheme 25: Carbotrifluoromethylation of N-arylacrylamides with CF3SO2Na/TBHP reported by Lei.
Scheme 26: Carbotrifluoromethylation of N-arylacrylamides with CF3SO2Na/(NH4)2S2O8.
Scheme 27: Metal-free carbotrifluoromethylation of N-arylacrylamides with CF3SO2Na/K2S2O8 reported by Wang.
Scheme 28: Metal-free carbotrifluoromethylation of N-arylacrylamides with CF3SO2Na/PIDA reported by Fu.
Scheme 29: Metal-free cascade trifluoromethylation/cyclisation of N-arylmethacrylamides (a) and enynes (b) wit...
Scheme 30: Trifluoromethylation/cyclisation of N-arylcinnamamides: Synthesis of 3,4-disubstituted dihydroquino...
Scheme 31: Trifluoromethylation/cyclisation of aromatic-containing unsaturated ketones.
Scheme 32: Chemo- and regioselective cascade trifluoromethylation/heteroaryl ipso-migration of unactivated alk...
Scheme 33: Copper-mediated 1,2-bis(trifluoromethylation) of alkenes.
Scheme 34: Trifluoromethylation of aromatics with CF3SO2Na reported by Langlois.
Scheme 35: Baran’s oxidative C–H trifluoromethylation of heterocycles.
Scheme 36: Trifluoromethylation of acetanilides and anilines.
Scheme 37: Trifluoromethylation of heterocycles in water.
Scheme 38: Trifluoromethylation of coumarins in a continuous-flow reactor.
Scheme 39: Oxidative trifluoromethylation of coumarins, quinolines and pyrimidinones.
Scheme 40: Oxidative trifluoromethylation of pyrimidinones and pyridinones.
Scheme 41: Phosphovanadomolybdic acid-catalysed direct C−H trifluoromethylation.
Scheme 42: Oxidative trifluoromethylation of imidazopyridines and imidazoheterocycles.
Scheme 43: Oxidative trifluoromethylation of imidazoheterocycles and imidazoles in ionic liquid/water.
Scheme 44: Oxidative trifluoromethylation of 8-aminoquinolines.
Scheme 45: Oxidative trifluoromethylation of various 8-aminoquinolines using the supported catalyst CS@Cu(OAc)2...
Scheme 46: Oxidative trifluoromethylation of the naphthylamide 70.
Scheme 47: Oxidative trifluoromethylation of various arenes in the presence of CF3SO2Na and sodium persulfate.
Scheme 48: Trifluoromethylation of electron-rich arenes and unsymmetrical biaryls with CF3SO2Na in the presenc...
Figure 1: Trifluoromethylated coumarin and flavone.
Scheme 49: Metal-free trifluoromethylation catalysed by a photoredox organocatalyst.
Scheme 50: Quinone-mediated trifluoromethylation of arenes and heteroarenes.
Scheme 51: Metal- and oxidant-free photochemical trifluoromethylation of arenes.
Scheme 52: Copper-mediated trifluoromethylation of arenediazonium tetrafluoroborates.
Scheme 53: Oxidative trifluoromethylation of aryl- and heteroarylboronic acids.
Scheme 54: Oxidative trifluoromethylation of aryl- and vinylboronic acids.
Scheme 55: Oxidative trifluoromethylation of unsaturated potassium organotrifluoroborates.
Scheme 56: Oxidative trifluoromethylation of (hetero)aryl- and vinyltrifluoroborates.
Scheme 57: Copper−catalysed decarboxylative trifluoromethylation of cinnamic acids.
Scheme 58: Iron-mediated decarboxylative trifluoromethylation of α,β-unsaturated carboxylic acids.
Scheme 59: Cu/Ag-catalysed decarboxylative trifluoromethylation of cinnamic acids.
Scheme 60: I2O5-Promoted decarboxylative trifluoromethylation of cinnamic acids.
Scheme 61: Silver(I)-catalysed denitrative trifluoromethylation of β-nitrostyrenes.
Scheme 62: Copper-catalysed direct trifluoromethylation of styrene derivatives.
Scheme 63: Transition-metal-free synthesis of β-trifluoromethylated enamines.
Scheme 64: I2O5-mediated iodotrifluoromethylation of alkynes.
Scheme 65: Silver-catalysed tandem trifluoromethylation/cyclisation of aryl isonitriles.
Scheme 66: Photoredox trifluoromethylation of 2-isocyanobiphenyls.
Scheme 67: Trifluoromethylation of potassium alkynyltrifluoroborates with CF3SO2Na.
Scheme 68: N-trifluoromethylation of nitrosoarenes with CF3SO2Na (SQ: semiquinone).
Scheme 69: Trifluoromethylation of disulfides with CF3SO2Na.
Scheme 70: Trifluoromethylation of thiols with CF3SO2Na/I2O5.
Scheme 71: Electrophilic trifluoromethylsulfenylation by means of CF3SO2Na/(EtO)2P(O)H/CuCl/DMSO.
Scheme 72: Electrophilic trifluoromethylsulfenylation by means of CF3SO2Na/(EtO)2P(O)H/TMSCl.
Scheme 73: Electrophilic trifluoromethylsulfenylation by means of CF3SO2Na/PPh3/N-chlorophthalimide.
Scheme 74: Electrophilic trifluoromethylsulfenylation by means of CF3SO2Na/PCl3.
Scheme 75: Electrophilic trifluoromethylsulfenylation by means of CF3SO2Na/PCl3.
Scheme 76: Trifluoromethylsulfenylation of aryl iodides with in situ generated CuSCF3 (DMI: 1,3-dimethyl-2-imi...
Scheme 77: Pioneering trifluoromethylsulfinylation of N, O, and C-nucleophiles.
Scheme 78: Trifluoromethylsulfinylation of (1R,2S)-ephedrine (Im: imidazole; DIEA: N,N-diisopropylethylamine).
Scheme 79: Trifluoromethylsulfinylation of substituted benzenes with CF3SO2Na/CF3SO3H.
Scheme 80: Trifluoromethylsulfinylation of indoles with CF3SO2Na/P(O)Cl3.
Scheme 81: Trifluoromethylsulfinylation of indoles with CF3SO2Na/PCl3.
Scheme 82: Formation of triflones from benzyl bromides (DMA: dimethylacetamide).
Scheme 83: Formation of α-trifluoromethylsulfonyl ketones, esters, and amides.
Scheme 84: Allylic trifluoromethanesulfonylation of aromatic allylic alcohols.
Scheme 85: Copper-catalysed couplings of aryl iodonium salts with CF3SO2Na.
Scheme 86: Palladium-catalysed trifluoromethanesulfonylation of aryl triflates and chlorides with CF3SO2Na.
Scheme 87: Copper-catalysed coupling of arenediazonium tetrafluoroborates with CF3SO2Na.
Scheme 88: Synthesis of phenyltriflone via coupling of benzyne with CF3SO2Na.
Scheme 89: Synthesis of 1-trifluoromethanesulfonylcyclopentenes from 1-alkynyl-λ3-bromanes and CF3SO2Na.
Scheme 90: One-pot synthesis of functionalised vinyl triflones.
Scheme 91: Regioselective synthesis of vinyltriflones from styrenes.
Scheme 92: Trifluoromethanesulfonylation of alkynyl(phenyl) iodonium tosylates by CF3SO2Na.
Scheme 93: Synthesis of thio- and selenotrifluoromethanesulfonates.
Rearrangements of organic peroxides and related processes
- Ivan A. Yaremenko,
- Vera A. Vil’,
- Dmitry V. Demchuk and
- Alexander O. Terent’ev
Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162
Graphical Abstract
Figure 1: The named transformations considered in this review.
Scheme 1: The Baeyer–Villiger oxidation.
Scheme 2: The general mechanism of the peracid-promoted Baeyer–Villiger oxidation.
Scheme 3: General mechanism of the Lewis acid-catalyzed Baeyer–Villiger rearrangement.
Scheme 4: The theoretically studied mechanism of the BV oxidation reaction promoted by H2O2 and the Lewis aci...
Scheme 5: Proton movements in the transition states of the Baeyer–Villiger oxidation.
Scheme 6: The dependence of the course of the Baeyer–Villiger oxidation on the type of O–O-bond cleavage in t...
Scheme 7: The acid-catalyzed Baeyer–Villiger oxidation of cyclic epoxy ketones 22.
Scheme 8: Oxidation of isophorone oxide 29.
Scheme 9: Synthesis of acyl phosphate 32 from acyl phosphonate 31.
Scheme 10: Synthesis of aflatoxin B2 (36).
Scheme 11: The Baeyer–Villiger rearrangement of ketones 37 to lactones 38.
Scheme 12: Synthesis of 3,4-dimethoxybenzoic acid (40) via Baeyer–Villiger oxidation.
Scheme 13: Oxone transforms α,β-unsaturated ketones 43 into vinyl acetates 44.
Scheme 14: The Baeyer–Villiger oxidation of ketones 45 using diaryl diselenide and hydrogen peroxide.
Scheme 15: Baeyer–Villiger oxidation of (E)-2-methylenecyclobutanones.
Scheme 16: Oxidation of β-ionone (56) by H2O2/(BnSe)2 with formation of (E)-2-(2,6,6-trimethylcyclohex-1-en-1-...
Scheme 17: The mechanism of oxidation of ketones 58a–f by hydrogen peroxide in the presence of arsonated polys...
Scheme 18: Oxidation of ketone (58b) by H2O2 to 6-methylcaprolactone (59b) catalyzed by Pt complex 66·BF4.
Scheme 19: Oxidation of ketones 67 with H2O2 in the presence of [(dppb}Pt(µ-OH)]22+.
Scheme 20: The mechanism of oxidation of ketones 67 in the presence of [(dppb}Pt(µ-OH)]22+ and H2O2.
Scheme 21: Oxidation of benzaldehydes 69 in the presence of the H2O2/MeReO3 system.
Scheme 22: Oxidation of acetophenones 72 in the presence of the H2O2/MeReO3 system.
Scheme 23: Baeyer–Villiger oxidation of 2-adamantanone (45c) in the presence of Sn-containing mesoporous silic...
Scheme 24: Aerobic Baeyer–Villiger oxidation of ketones 76 using metal-free carbon.
Scheme 25: A regioselective Baeyer-Villiger oxidation of functionalized cyclohexenones 78 into a dihydrooxepin...
Scheme 26: The oxidation of aldehydes and ketones 80 by H2O2 catalyzed by Co4HP2Mo15V3O62.
Scheme 27: The cleavage of ketones 82 with hydrogen peroxide in alkaline solution.
Scheme 28: Oxidation of ketones 85 to esters 86 with H2O2–urea in the presence of KHCO3.
Scheme 29: Mechanism of the asymmetric oxidation of cyclopentane-1,2-dione 87a with the Ti(OiPr)4/(+)DET/t-BuO...
Scheme 30: The oxidation of cis-4-tert-butyl-2-fluorocyclohexanone (93) with m-chloroperbenzoic acid.
Scheme 31: The mechanism of the asymmetric oxidation of 3-substituted cyclobutanone 96a in the presence of chi...
Scheme 32: Enantioselective Baeyer–Villiger oxidation of cyclic ketones 98.
Scheme 33: Regio- and enantioselective Baeyer–Villiger oxidation of cyclic ketones 101.
Scheme 34: The proposed mechanism of the Baeyer–Villiger oxidation of acetal 105f.
Scheme 35: Synthesis of hydroxy-10H-acridin-9-one 117 from tetramethoxyanthracene 114.
Scheme 36: The Baeyer–Villiger oxidation of the fully substituted pyrrole 120.
Scheme 37: The Criegee rearrangement.
Scheme 38: The mechanism of the Criegee reaction of a peracid with a tertiary alcohol 122.
Scheme 39: Criegee rearrangement of decaline ethylperoxoate 127 into ketal 128.
Scheme 40: The ionic cleavage of 2-methoxy-2-propyl perester 129.
Scheme 41: The Criegee rearrangement of α-methoxy hydroperoxide 136.
Scheme 42: Synthesis of enol esters and acetals via the Criegee rearrangement.
Scheme 43: Proposed mechanism of the transformation of 1-hydroperoxy-2-oxabicycloalkanones 147a–d.
Scheme 44: Transformation of 3-hydroxy-1,2-dioxolanes 151 into diketone derivatives 152.
Scheme 45: Criegee rearrangement of peroxide 153 with the mono-, di-, and tri-O-insertion.
Scheme 46: The sequential Criegee rearrangements of adamantanes 157a,b.
Scheme 47: Synthesis of diaryl carbonates 160a–d from triarylmethanols 159a–d through successive oxygen insert...
Scheme 48: The synthesis of sesquiterpenes 162 from ketone 161 with a Criegee rearrangement as one key step.
Scheme 49: Synthesis of trans-hydrindan derivatives 164, 165.
Scheme 50: The Hock rearrangement.
Scheme 51: The general scheme of the cumene process.
Scheme 52: The Hock rearrangement of aliphatic hydroperoxides.
Scheme 53: The mechanism of solvolysis of brosylates 174a–c and spiro cyclopropyl carbinols 175a–c in THF/H2O2....
Scheme 54: The fragmentation mechanism of hydroperoxy acetals 178 to esters 179.
Scheme 55: The acid-catalyzed rearrangement of phenylcyclopentyl hydroperoxide 181.
Scheme 56: The peroxidation of tertiary alcohols in the presence of a catalytic amount of acid.
Scheme 57: The acid-catalyzed reaction of bicyclic secondary alcohols 192 with hydrogen peroxide.
Scheme 58: The photooxidation of 5,6-disubstituted 3,4-dihydro-2H-pyrans 196.
Scheme 59: The oxidation of tertiary alcohols 200a–g, 203a,b, and 206.
Scheme 60: Transformation of functional peroxide 209 leading to 2,3-disubstitued furans 210 in one step.
Scheme 61: The synthesis of carbazoles 213 via peroxide rearrangement.
Scheme 62: The construction of C–N bonds using the Hock rearrangement.
Scheme 63: The synthesis of moiety 218 from 217 which is a structural motif in the antitumor–antibiotic of CC-...
Scheme 64: The in vivo oxidation steps of cholesterol (219) by singlet oxygen.
Scheme 65: The proposed mechanism of the rearrangement of cholesterol-5α-OOH 220.
Scheme 66: Photochemical route to artemisinin via Hock rearrangement of 223.
Scheme 67: The Kornblum–DeLaMare rearrangement.
Scheme 68: Kornblum–DeLaMare transformation of 1-phenylethyl tert-butyl peroxide (225).
Scheme 69: The synthesis 4-hydroxyenones 230 from peroxide 229.
Scheme 70: The Kornblum–DeLaMare rearrangement of peroxide 232.
Scheme 71: The reduction of peroxide 234.
Scheme 72: The Kornblum–DeLaMare rearrangement of endoperoxide 236.
Scheme 73: The rearrangement of peroxide 238 under Kornblum–DeLaMare conditions.
Scheme 74: The proposed mechanism of rearrangement of peroxide 238.
Scheme 75: The Kornblum–DeLaMare rearrangement of peroxides 242a,b.
Scheme 76: The base-catalyzed rearrangements of bicyclic endoperoxides having electron-withdrawing substituent...
Scheme 77: The base-catalyzed rearrangements of bicyclic endoperoxides 249a,b having electron-donating substit...
Scheme 78: The base-catalyzed rearrangements of bridge-head substituted bicyclic endoperoxides 251a,b.
Scheme 79: The Kornblum–DeLaMare rearrangement of hydroperoxide 253.
Scheme 80: Synthesis of β-hydroxy hydroperoxide 254 from endoperoxide 253.
Scheme 81: The amine-catalyzed rearrangement of bicyclic endoperoxide 263.
Scheme 82: The base-catalyzed rearrangement of meso-endoperoxide 268 into 269.
Scheme 83: The photooxidation of 271 and subsequent Kornblum–DeLaMare reaction.
Scheme 84: The Kornblum–DeLaMare rearrangement as one step in the oxidation reaction of enamines.
Scheme 85: The Kornblum–DeLaMare rearrangement of 3,5-dihydro-1,2-dioxenes 284, 1,2-dioxanes 286, and tert-but...
Scheme 86: The Kornblum–DeLaMare rearrangement of epoxy dioxanes 290a–d.
Scheme 87: Rearrangement of prostaglandin H2 292.
Scheme 88: The synthesis of epicoccin G (297).
Scheme 89: The Kornblum–DeLaMare rearrangement used in the synthesis of phomactin A.
Scheme 90: The Kornblum–DeLaMare rearrangement in the synthesis of 3H-quinazolin-4-one 303.
Scheme 91: The Kornblum–DeLaMare rearrangement in the synthesis of dolabriferol (308).
Scheme 92: Sequential transformation of 3-substituted 2-pyridones 309 into 3-hydroxypyridine-2,6-diones 311 in...
Scheme 93: The Kornblum–DeLaMare rearrangement of peroxide 312 into hydroxy enone 313.
Scheme 94: The Kornblum–DeLaMare rearrangement in the synthesis of polyfunctionalized carbonyl compounds 317.
Scheme 95: The Kornblum–DeLaMare rearrangement in the synthesis of (Z)-β-perfluoroalkylenaminones 320.
Scheme 96: The Kornblum–DeLaMare rearrangement in the synthesis of γ-ketoester 322.
Scheme 97: The Kornblum–DeLaMare rearrangement in the synthesis of diterpenoids 326 and 328.
Scheme 98: The synthesis of natural products hainanolidol (331) and harringtonolide (332) from peroxide 329.
Scheme 99: The synthesis of trans-fused butyrolactones 339 and 340.
Scheme 100: The synthesis of leucosceptroid C (343) and leucosceptroid P (344) via the Kornblum–DeLaMare rearra...
Scheme 101: The Dakin oxidation of arylaldehydes or acetophenones.
Scheme 102: The mechanism of the Dakin oxidation.
Scheme 103: A solvent-free Dakin reaction of aromatic aldehydes 356.
Scheme 104: The organocatalytic Dakin oxidation of electron-rich arylaldehydes 358.
Scheme 105: The Dakin oxidation of electron-rich arylaldehydes 361.
Scheme 106: The Dakin oxidation of arylaldehydes 358 in water extract of banana (WEB).
Scheme 107: A one-pot approach towards indolo[2,1-b]quinazolines 364 from indole-3-carbaldehydes 363 through th...
Scheme 108: The synthesis of phenols 367a–c from benzaldehydes 366a-c via acid-catalyzed Dakin oxidation.
Scheme 109: Possible transformation paths of the highly polarized boric acid coordinated H2O2–aldehyde adduct 3...
Scheme 110: The Elbs oxidation of phenols 375 to hydroquinones.
Scheme 111: The mechanism of the Elbs persulfate oxidation of phenols 375 affording p-hydroquinones 376.
Scheme 112: Oxidation of 2-pyridones 380 under Elbs persulfate oxidation conditions.
Scheme 113: Synthesis of 3-hydroxy-4-pyridone (384) via an Elbs oxidation of 4-pyridone (382).
Scheme 114: The Schenck rearrangement.
Scheme 115: The Smith rearrangement.
Scheme 116: Three main pathways of the Schenck rearrangement.
Scheme 117: The isomerization of hydroperoxides 388 and 389.
Scheme 118: Trapping of dioxacyclopentyl radical 392 by oxygen.
Scheme 119: The hypothetical mechanism of the Schenck rearrangement of peroxide 394.
Scheme 120: The autoxidation of oleic acid (397) with the use of labeled isotope 18O2.
Scheme 121: The rearrangement of 18O-labeled hydroperoxide 400 under an atmosphere of 16O2.
Scheme 122: The rearrangement of the oleate-derived allylic hydroperoxides (S)-421 and (R)-425.
Scheme 123: Mechanisms of Schenck and Smith rearrangements.
Scheme 124: The rearrangement and cyclization of 433.
Scheme 125: The Wieland rearrangement.
Scheme 126: The rearrangement of bis(triphenylsilyl) 439 or bis(triphenylgermyl) 441 peroxides.
Scheme 127: The oxidative transformation of cyclic ketones.
Scheme 128: The hydroxylation of cyclohexene (447) in the presence of tungstic acid.
Scheme 129: The oxidation of cyclohexene (447) under the action of hydrogen peroxide.
Scheme 130: The reaction of butenylacetylacetone 455 with hydrogen peroxide.
Scheme 131: The oxidation of bridged 1,2,4,5-tetraoxanes.
Scheme 132: The proposed mechanism for the oxidation of bridged 1,2,4,5-tetraoxanes.
Scheme 133: The rearrangement of ozonides.
Scheme 134: The acid-catalyzed oxidative rearrangement of malondialdehydes 462 under the action of H2O2.
Scheme 135: Pathways of the Lewis acid-catalyzed cleavage of dialkyl peroxides 465 and ozonides 466.
Scheme 136: The mechanism of the transformation of (tert-butyldioxy)cyclohexanedienones 472.
Scheme 137: The synthesis of Vitamin K3 from 472a.
Scheme 138: Proposed mechanism for the transformation of 478d into silylated endoperoxide 479d.
Scheme 139: The rearrangement of hydroperoxide 485 to form diketone 486.
Scheme 140: The base-catalyzed rearrangement of cyclic peroxides 488a–g.
Scheme 141: Synthesis of chiral epoxides and aldols from peroxy hemiketals 491.
Scheme 142: The multistep transformation of (R)-carvone (494) to endoperoxides 496a–e.
Scheme 143: The decomposition of anthracene endoperoxide 499.
Scheme 144: Synthesis of esters 503 from aldehydes 501 via rearrangement of peroxides 502.
Scheme 145: Two possible paths for the base-promoted decomposition of α-azidoperoxides 502.
Scheme 146: The Story decomposition of cyclic diperoxide 506a.
Scheme 147: The Story decomposition of cyclic triperoxide 506b.
Scheme 148: The thermal rearrangement of endoperoxides A into diepoxides B.
Scheme 149: The transformation of peroxide 510 in the synthesis of stemolide (511).
Scheme 150: The possible mechanism of the rearrangement of endoperoxide 261g.
Scheme 151: The photooxidation of indene 517.
Scheme 152: The isomerization of ascaridole (523).
Scheme 153: The isomerization of peroxide 525.
Scheme 154: The thermal transformation of endoperoxide 355.
Scheme 155: The photooxidation of cyclopentadiene (529) at a temperature higher than 0 °C.
Scheme 156: The thermal rearrangement of endoperoxides 538a,b.
Scheme 157: The transformation of peroxides 541.
Scheme 158: The thermal rearrangements of strained cyclic peroxides.
Scheme 159: The thermal rearrangement of diacyl peroxide 551 in the synthesis of C4-epi-lomaiviticin B core 553....
Scheme 160: The 1O2 oxidation of tryptophan (554) and rearrangement of dioxetane intermediate 555.
Scheme 161: The Fe(II)-promoted cleavage of aryl-substituted bicyclic peroxides.
Scheme 162: The proposed mechanism of the Fe(II)-promoted rearrangement of 557a–c.
Scheme 163: The reaction of dioxolane 563 with Fe(II) sulfate.
Scheme 164: Fe(II)-promoted rearrangement of 1,2-dioxane 565.
Scheme 165: Fe(II) cysteinate-promoted rearrangement of 1,2-dioxolane 568.
Scheme 166: The transformation of 1,2-dioxanes 572a–c under the action of FeCl2.
Scheme 167: Fe(II) cysteinate-promoted transformation of tetraoxane 574.
Scheme 168: The CoTPP-catalyzed transformation of bicyclic endoperoxides 600a–d.
Scheme 169: The CoTPP-catalyzed transformation of epoxy-1,2-dioxanes.
Scheme 170: The Ru(II)-catalyzed reactions of 1,4-endoperoxide 261g.
Scheme 171: The Ru(II)-catalyzed transformation as a key step in the synthesis of elyiapyrone A (610) from 1,4-...
Scheme 172: Peroxides with antimalarial activity.
Scheme 173: The interaction of iron ions with artemisinin (616).
Scheme 174: The interaction of FeCl2 with 1,2-dioxanes 623, 624.
Scheme 175: The mechanism of reaction 623 and 624 with Fe(II)Cl2.
Scheme 176: The reaction of bicyclic natural endoperoxides G3-factors 631–633 with FeSO4.
Scheme 177: The transformation of terpene cardamom peroxide 639.
Scheme 178: The different ways of the cleavage of tetraoxane 643.
Scheme 179: The LC–MS analysis of interaction of tetraoxane 646 with iron(II)heme 647.
Scheme 180: The rearrangement of 3,6-epidioxy-1,10-bisaboladiene (EDBD, 649).
Scheme 181: Easily oxidized substrates.
Scheme 182: Biopathway of synthesis of prostaglandins.
Scheme 183: The reduction and rearrangements of isoprostanes.
Scheme 184: The partial mechanism for linoleate 658 oxidation.
Scheme 185: The transformation of lipid hydroperoxide.
Scheme 186: The acid-catalyzed cleavage of the product from free-radical oxidation of cholesterol (667).
Scheme 187: Two pathways of catechols oxidation.
Scheme 188: Criegee-like or Hock-like rearrangement of the intermediate hydroperoxide 675 in dioxygenase enzyme...
Scheme 189: Carotinoides 679 cleavage by carotenoid cleavage dioxygenases.
Synthesis of the furo[2,3-b]chromene ring system of hyperaspindols A and B
- Danielle L. Paterson and
- David Barker
Beilstein J. Org. Chem. 2015, 11, 265–270, doi:10.3762/bjoc.11.29
- ]chromenes. Compound which contain this motif, such as albanol A and australisine A, display potent bioactive properties including hypotensive, anticancer, antimicrobial and antimalarial activity [10][11][12]. The unique ring system found in the hyperaspidinols combined with the potent biological activities
Graphical Abstract
Figure 1: Hyperaspidinols A (1) and B (2) and other compounds 3-6 from Hypericum chinense.
Figure 2: Hyperaspidinol A (1), target compound 7 and proposed precursors.
Scheme 1: Reagents and conditions: (i) triethylphosphonoacetate, DBU, THF, 48 h, 94%; (ii) H2, 10% Pd/C, EtOA...
Scheme 2: Reagents and conditions: (i) H3C(CH3O)NH·HCl, n-BuLi, THF, −78 °C, 4 h, 81%; (ii) 1-bromo-3,4-methy...
Figure 3: NOESY correlations in isomers 7a and 7b.
Figure 4: 3D representation of 7a.
Figure 5: 3D representation of 7b.
Figure 6: Possible mechanism for the formation of furo[2,3-b]chromenes 7a and 7b.
(2R,1'S,2'R)- and (2S,1'S,2'R)-3-[2-Mono(di,tri)fluoromethylcyclopropyl]alanines and their incorporation into hormaomycin analogues
- Armin de Meijere,
- Sergei I. Kozhushkov,
- Dmitrii S. Yufit,
- Christian Grosse,
- Marcel Kaiser and
- Vitaly A. Raev
Beilstein J. Org. Chem. 2014, 10, 2844–2857, doi:10.3762/bjoc.10.302
- production of various streptomycetes including the producing strain itself, and an exceptionally selective inhibitory effect on coryneform bacteria [3][4], an interesting antimalarial activity was discovered [13]. It was this property that led us to consider the synthesis of even more analogues of 1. Bearing
Graphical Abstract
Figure 1: Structure and absolute configuration of hormaomycin (1), its fluoromethyl-substituted analogues 8a–c...
Figure 2: Structures of the Belokon'-type glycine complexes (BGC) (R)- and (S)-10.
Scheme 1: Intended routes to methyl trans-2-(fluormethyl)cyclopropanecarboxylates 14a–c.
Scheme 2: Synthesis of trans-(2-trifluoromethyl)cyclopropanecarboxylic acid (24).
Scheme 3: Preparation of racemic trans-2-(fluoromethyl)cyclopropylmethyl iodides 11a–c and their conversion t...
Figure 3: Structure and absolute configurations of the nickel(II) complexes (2S,1'R,2'S)-26a, (2S,1'R,2'S)-26b...
Figure 4: Structure and absolute configuration of nickel(II) complex (R,R,R)-28 in the crystal. Hydrogen atom...
Scheme 4: Mechanism of epimerization of the threonine nickel(II) complex 29.
Scheme 5: A new general approach to (2S,3R)-β-methylarylalanines 3 by alkylation of the glycine nickel(II) co...
Figure 5: Structure and absolute configuration of nickel(II) complex (2S,3S)-32 in the crystal. Hydrogen atom...
Scheme 6: Synthesis of the cyclohexadepsipeptides 52a–c for the hormaomycin analogues 8a–c with 3-(2'-fluorom...
Scheme 7: Synthesis of hormaomycin analogues with a: trifluoromethyl-, b: difluoromethyl-, c: monofluoromethy...
Figure 6: Two derivatives 58 and 59 of cyclohexadepsipeptide 52a containing the (trifluoromethylcyclopropyl)a...
Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products
- Alexander O. Terent'ev,
- Dmitry A. Borisov,
- Vera A. Vil’ and
- Valery M. Dembitsky
Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6
- considerable role. In medicinal chemistry of peroxides, artemisinin a natural peroxide exhibiting high antimalarial activity, is the most important drug in use for approximately 30 years. Artemisinin was isolated in 1971 from leaves of annual wormwood (Artemesia annua) [49][50][51]; the 1,2,4-trioxane ring V
- pharmacophore was synthesized in two steps by the oxidation of alcohol 156 with H5IO6/RuCl3 followed by amidation of the acid 157 (Scheme 39) [88]. It was shown that compound 158 exhibits antimalarial activity comparable with that of artemisinin [88]. Plakinic acids belong to a large family of natural products
- , neither sodium hydride nor sodium salt 183 cleave the ozonide ring to a substantial degree. The resulting 1,2,4-trioxolanes 188 and 189 exhibit high in vitro antimalarial activity comparable with that of artemisinin and in vivo even higher activity than that of artemisinin [93]. Aminoquinoline-containing
Graphical Abstract
Figure 1: Five and six-membered cyclic peroxides.
Figure 2: Artemisinin and semi-synthetic derivatives.
Scheme 1: Synthesis of 3-hydroxy-1,2-dioxolanes 3a–c.
Scheme 2: Synthesis of dioxolane 6.
Scheme 3: Photooxygenation of oxazolidines 7a–d with formation of spiro-fused oxazolidine-containing dioxolan...
Scheme 4: Oxidation of cyclopropanes 10a–e and 11a–e with preparation of 1,2-dioxolanes 12a–e.
Scheme 5: VO(acac)2-catalyzed oxidation of silylated bicycloalkanols 13a–c.
Scheme 6: Mn(II)-catalyzed oxidation of cyclopropanols 15a–g.
Scheme 7: Oxidation of aminocyclopropanes 20a–c.
Scheme 8: Synthesis of aminodioxolanes 24.
Figure 3: Trifluoromethyl-containing dioxolane 25.
Scheme 9: Synthesis of 1,2-dioxolanes 27a–e by the oxidation of cyclopropanes 26a–e.
Scheme 10: Photoinduced oxidation of methylenecyclopropanes 28.
Scheme 11: Irradiation-mediated oxidation.
Scheme 12: Application of diazene 34 for dioxolane synthesis.
Scheme 13: Mn(OAc)3-catalyzed cooxidation of arylacetylenes 37a–h and acetylacetone with atmospheric oxygen.
Scheme 14: Peroxidation of (2-vinylcyclopropyl)benzene (40).
Scheme 15: Peroxidation of 1,4-dienes 43a,b.
Scheme 16: Peroxidation of 1,5-dienes 46.
Scheme 17: Peroxidation of oxetanes 53a,b.
Scheme 18: Peroxidation of 1,6-diene 56.
Scheme 19: Synthesis of 3-alkoxy-1,2-dioxolanes 62a,b.
Scheme 20: Synthesis of spiro-bis(1,2-dioxolane) 66.
Scheme 21: Synthesis of dispiro-1,2-dioxolanes 68, 70, 71.
Scheme 22: Synthesis of spirohydroperoxydioxolanes 75a,b.
Scheme 23: Synthesis of spirohydroperoxydioxolane 77 and dihydroperoxydioxolane 79.
Scheme 24: Ozonolysis of azepino[4,5-b]indole 80.
Scheme 25: SnCl4-mediated fragmentation of ozonides 84a–l in the presence of allyltrimethylsilane.
Scheme 26: SnCl4-mediated fragmentation of bicyclic ozonide 84m in the presence of allyltrimethylsilane.
Scheme 27: MCl4-mediated fragmentation of alkoxyhydroperoxides 96 in the presence of allyltrimethylsilane.
Scheme 28: SnCl4-catalyzed reaction of monotriethylsilylperoxyacetal 108 with alkene 109.
Scheme 29: SnCl4-catalyzed reaction of triethylsilylperoxyacetals 111 with alkenes.
Scheme 30: Desilylation of tert-butyldimethylsilylperoxy ketones 131a,b followed by cyclization.
Scheme 31: Deprotection of peroxide 133 followed by cyclization.
Scheme 32: Asymmetric peroxidation of methyl vinyl ketones 137a–e.
Scheme 33: Et2NH-catalyzed intramolecular cyclization.
Scheme 34: Synthesis of oxodioxolanes 143a–j.
Scheme 35: Haloperoxidation accompanied by intramolecular ring closure.
Scheme 36: Oxidation of triterpenes 149a–d with Na2Cr2O7/N-hydroxysuccinimide.
Scheme 37: Curtius and Wolff rearrangements to form 1,2-dioxolane ring-retaining products.
Scheme 38: Oxidative desilylation of peroxide 124.
Scheme 39: Synthesis of dioxolane 158, a compound containing the aminoquinoline antimalarial pharmacophore.
Scheme 40: Diastereomers of plakinic acid A, 162a and 162b.
Scheme 41: Ozonolysis of alkenes.
Scheme 42: Cross-ozonolysis of alkenes 166 with carbonyl compounds.
Scheme 43: Ozonolysis of the bicyclic cyclohexenone 168.
Scheme 44: Cross-ozonolysis of enol ethers 172a,b with cyclohexanone.
Scheme 45: Griesbaum co-ozonolysis.
Scheme 46: Reactions of aryloxiranes 177a,b with oxygen.
Scheme 47: Intramolecular formation of 1,2,4-trioxolane 180.
Scheme 48: Formation of 1,2,4-trioxolane 180 by the reaction of 1,5-ketoacetal 181 with H2O2.
Scheme 49: 1,2,4-Trioxolane 186 with tetrazole fragment.
Scheme 50: 1,2,4-Trioxolane 188 with a pyridine fragment.
Scheme 51: 1,2,4-Trioxolane 189 with pyrimidine fragment.
Scheme 52: Synthesis of aminoquinoline-containing 1,2,4-trioxalane 191.
Scheme 53: Synthesis of arterolane.
Scheme 54: Oxidation of diarylheptadienes 197a–c with singlet oxygen.
Scheme 55: Synthesis of hexacyclinol peroxide 200.
Scheme 56: Oxidation of enone 201 and enenitrile 203 with singlet oxygen.
Scheme 57: Synthesis of 1,2-dioxanes 207 by oxidative coupling of carbonyl compounds 206 and alkenes 205.
Scheme 58: 1,2-Dioxanes 209 synthesis by co-oxidation of 1,5-dienes 208 and thiols.
Scheme 59: Synthesis of bicyclic 1,2-dioxanes 212 with aryl substituents.
Scheme 60: Isayama–Mukaiyama peroxysilylation of 1,5-dienes 213 followed by desilylation under acidic conditio...
Scheme 61: Synthesis of bicycle 218 with an 1,2-dioxane ring.
Scheme 62: Intramolecular cyclization with an oxirane-ring opening.
Scheme 63: Inramolecular cyclization with the oxetane-ring opening.
Scheme 64: Intramolecular cyclization with the attack on a keto group.
Scheme 65: Peroxidation of the carbonyl group in unsaturated ketones 228 followed by cyclization of hydroperox...
Scheme 66: CsOH and Et2NH-catalyzed cyclization.
Scheme 67: Preparation of peroxyplakoric acid methyl ethers A and D.
Scheme 68: Hg(OAc)2 in 1,2-dioxane synthesis.
Scheme 69: Reaction of 1,4-diketones 242 with hydrogen peroxide.
Scheme 70: Inramolecular cyclization with oxetane-ring opening.
Scheme 71: Inramolecular cyclization with MsO fragment substitution.
Scheme 72: Synthesis of 1,2-dioxane 255a, a structurally similar compound to natural peroxyplakoric acids.
Scheme 73: Synthesis of 1,2-dioxanes based on the intramolecular cyclization of hydroperoxides containing C=C ...
Scheme 74: Use of BCIH in the intramolecular cyclization.
Scheme 75: Palladium-catalyzed cyclization of δ-unsaturated hydroperoxides 271a–e.
Scheme 76: Intramolecular cyclization of unsaturated peroxyacetals 273a–d.
Scheme 77: Allyltrimethylsilane in the synthesis of 1,2-dioxanes 276a–d.
Scheme 78: Intramolecular cyclization using the electrophilic center of the peroxycarbenium ion 279.
Scheme 79: Synthesis of bicyclic 1,2-dioxanes.
Scheme 80: Preparation of 1,2-dioxane 286.
Scheme 81: Di(tert-butyl)peroxalate-initiated radical cyclization of unsaturated hydroperoxide 287.
Scheme 82: Oxidation of 1,4-betaines 291a–d.
Scheme 83: Synthesis of aminoquinoline-containing 1,2-dioxane 294.
Scheme 84: Synthesis of the sulfonyl-containing 1,2-dioxane.
Scheme 85: Synthesis of the amido-containing 1,2-dioxane 301.
Scheme 86: Reaction of singlet oxygen with the 1,3-diene system 302.
Scheme 87: Synthesis of (+)-premnalane А and 8-epi-premnalane A.
Scheme 88: Synthesis of the diazo group containing 1,2-dioxenes 309a–e.
Figure 4: Plakortolide Е.
Scheme 89: Synthesis of 6-epiplakortolide Е.
Scheme 90: Application of Bu3SnH for the preparation of tetrahydrofuran-containing bicyclic peroxides 318a,b.
Scheme 91: Application of Bu3SnH for the preparation of lactone-containing bicyclic peroxides 320a–f.
Scheme 92: Dihydroxylation of the double bond in the 1,2-dioxene ring 321 with OsO4.
Scheme 93: Epoxidation of 1,2-dioxenes 324.
Scheme 94: Cyclopropanation of the double bond in endoperoxides 327.
Scheme 95: Preparation of pyridazine-containing bicyclic endoperoxides 334a–c.
Scheme 96: Synthesis of 1,2,4-trioxanes 337 by the hydroperoxidation of unsaturated alcohols 335 with 1O2 and ...
Scheme 97: Synthesis of sulfur-containing 1,2,4-trioxanes 339.
Scheme 98: BF3·Et2O-catalyzed synthesis of the 1,2,4-trioxanes 342a–g.
Scheme 99: Photooxidation of enol ethers or vinyl sulfides 343.
Scheme 100: Synthesis of tricyclic peroxide 346.
Scheme 101: Reaction of endoperoxides 348a,b derived from cyclohexadienes 347a,b with 1,4-cyclohexanedione.
Scheme 102: [4 + 2]-Cycloaddition of singlet oxygen to 2Н-pyrans 350.
Scheme 103: Synthesis of 1,2,4-trioxanes 354 using peroxysilylation stage.
Scheme 104: Epoxide-ring opening in 355 with H2O2 followed by the condensation of hydroxy hydroperoxides 356 wi...
Scheme 105: Peroxidation of unsaturated ketones 358 with the H2O2/CF3COOH/H2SO4 system.
Scheme 106: Synthesis of 1,2,4-trioxanes 362 through Et2NH-catalyzed intramolecular cyclization.
Scheme 107: Reduction of the double bond in tricyclic peroxides 363.
Scheme 108: Horner–Wadsworth–Emmons reaction in the presence of peroxide group.
Scheme 109: Reduction of ester group by LiBH4 in the presence of 1,2,4-trioxane moiety.
Scheme 110: Reductive amination of keto-containing 1,2,4-trioxane 370.
Scheme 111: Reductive amination of keto-containing 1,2,4-trioxane and a Fe-containing moiety.
Scheme 112: Acid-catalyzed reactions of Н2О2 with ketones and aldehydes 374.
Scheme 113: Cyclocondensation of carbonyl compounds 376a–d using Me3SiOOSiMe3/CF3SO3SiMe3.
Scheme 114: Peroxidation of 4-methylcyclohexanone (378).
Scheme 115: Synthesis of symmetrical tetraoxanes 382a,b from aldehydes 381a,b.
Scheme 116: Synthesis of unsymmetrical tetraoxanes using of MeReO3.
Scheme 117: Synthesis of symmetrical tetraoxanes using of MeReO3.
Scheme 118: Synthesis of symmetrical tetraoxanes using of MeReO3.
Scheme 119: MeReO3 in the synthesis of symmetrical tetraoxanes with the use of aldehydes.
Scheme 120: Preparation of unsymmmetrical 1,2,4,5-tetraoxanes with high antimalarial activity.
Scheme 121: Re2O7-Catalyzed synthesis of tetraoxanes 398.
Scheme 122: H2SO4-Catalyzed synthesis of steroidal tetraoxanes 401.
Scheme 123: HBF4-Catalyzed condensation of bishydroperoxide 402 with 1,4-cyclohexanedione.
Scheme 124: BF3·Et2O-Catalyzed reaction of gem-bishydroperoxides 404 with enol ethers 405 and acetals 406.
Scheme 125: HBF4-Catalyzed cyclocondensation of bishydroperoxide 410 with ketones.
Scheme 126: Synthesis of symmetrical and unsymmetrical tetraoxanes 413 from benzaldehydes 412.
Scheme 127: Synthesis of bridged 1,2,4,5-tetraoxanes 415a–l from β-diketones 414a–l and H2O2.
Scheme 128: Dimerization of zwitterions 417.
Scheme 129: Ozonolysis of verbenone 419.
Scheme 130: Ozonolysis of O-methyl oxime 424.
Scheme 131: Peroxidation of 1,1,1-trifluorododecan-2-one 426 with oxone.
Scheme 132: Intramolecular cyclization of dialdehyde 428 with H2O2.
Scheme 133: Tetraoxanes 433–435 as by-products in peroxidation of ketals 430–432.
Scheme 134: Transformation of triperoxide 436 in diperoxide 437.
Scheme 135: Preparation and structural modifications of tetraoxanes.
Scheme 136: Structural modifications of steroidal tetraoxanes.
Scheme 137: Synthesis of 1,2,4,5-tetraoxane 454 containing the fluorescent moiety.
Scheme 138: Synthesis of tetraoxane 458 (RKA182).
Synthesis and biological activities of the respiratory chain inhibitor aurachin D and new ring versus chain analogues
- Xu-Wen Li,
- Jennifer Herrmann,
- Yi Zang,
- Philippe Grellier,
- Soizic Prado,
- Rolf Müller and
- Bastien Nay
Beilstein J. Org. Chem. 2013, 9, 1551–1558, doi:10.3762/bjoc.9.176
- at an IC50 around 20 ng/mL (i.e., aurachins B, C and E, whereas aurachin D was 100- to 200-fold less active) [6]. This antimalarial activity was comparable to that of endochin (5) [13][14] and 2-methyl-4(1H)-quinolone analogues as determined in the course of important structure–activity optimization
Graphical Abstract
Figure 1: The 2-methyl-4(1H)-quinolone compounds: aurachins and endochin.
Scheme 1: Synthesis of aurachin D (4) and geranyl (9), prenyl (10) and methyl (11) analogues.
Scheme 2: Strategy toward the heterocyclic core of aurachin H.
Figure 2: (A) Loss of mitochondrial membrane potential in human U-2 OS osteosarcoma cells that were treated w...
Synthesis of 2-amino-3-arylpropan-1-ols and 1-(2,3-diaminopropyl)-1,2,3-triazoles and evaluation of their antimalarial activity
- Matthias D’hooghe,
- Stéphanie Vandekerckhove,
- Karen Mollet,
- Karel Vervisch,
- Stijn Dekeukeleire,
- Liesbeth Lehoucq,
- Carmen Lategan,
- Peter J. Smith,
- Kelly Chibale and
- Norbert De Kimpe
Beilstein J. Org. Chem. 2011, 7, 1745–1752, doi:10.3762/bjoc.7.205
- antiplasmodial activity against both a chloroquine-sensitive and a chloroquine-resistant strain of Plasmodium falciparum with IC50-values of ≤25 μM. Keywords: aminopropanes; antimalarial activity; aziridines; β-lactams; ring opening; Introduction Malaria remains a major issue in health control, especially in
Graphical Abstract
Figure 1: Functionalized aminopropanes as potential antimalarial agents.
Scheme 1: Synthesis of aminopropanols 6, 8 and 9.
Scheme 2: Synthesis of syn-aminopropan-1,3-diols 12.
Scheme 3: Synthesis of 2-[(1,2,3-triazol-1-yl)methyl]aziridines 15 and their transformation into 1,2,3-triami...
Synthesis of spiroannulated and 3-arylated 1,2,4-trioxanes from mesitylol and methyl 4-hydroxytiglate by photooxygenation and peroxyacetalization
- Axel G. Griesbeck,
- Lars-Oliver Höinck and
- Jörg M. Neudörfl
Beilstein J. Org. Chem. 2010, 6, No. 61, doi:10.3762/bjoc.6.61
- 1.460 (3 compounds) to 1.482 (4 compounds). All compounds 10a–h investigated by us fall into this range, 10a,g,h showing the longest O1-O2 bond distances. With regards to antimalarial activity, all 4-arylated 1,2,4-trioxanes exhibited low in vitro activities (EC50/plasmodium falciparum > 50 μM) with the
Graphical Abstract
Figure 1: Antimalaria active natural artemisinin 1 and the spirobicyclic 1,2,4-trioxane derivative 2 show the...
Scheme 1: Singlet oxygen ene reaction of methyl 4-hydroxytiglate (3) and mesitylol (6) under solid-phase cond...
Scheme 2: 1,2,4-trioxane 9c and bis-trioxane 8a,b formation from the bifunctional cyclohexa-1,4-dione.
Figure 2: Structure of the spirobicyclic trioxane 5c in the crystal.
Scheme 3: BF3-catalyzed acetalization of hydroperoxide 4 with benzaldehyde derivatives.
Figure 3: Structure of the 3-arylated trioxane 10b in the crystal.
Figure 4: Structure of the p-bromophenyl derivative 10d in the crystal lattice (disordered water molecules in...
Figure 5: Numbering of 3-aryl-1,2,4-trioxanes 10 and relevant bonds; structure of artemether (AM).
