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Search for "anticancer agents" in Full Text gives 56 result(s) in Beilstein Journal of Organic Chemistry.
Development of a chemical scaffold for inhibiting nonribosomal peptide synthetases in live bacterial cells
- Fumihiro Ishikawa,
- Sho Konno,
- Hideaki Kakeya and
- Genzoh Tanabe
Beilstein J. Org. Chem. 2024, 20, 445–451, doi:10.3762/bjoc.20.39
- ; Introduction Nonribosomal peptides (NRPs) exhibit various biological activities and have been used as therapeutic agents, such as antibiotics, anticancer agents, and immunosuppressants [1]. Additionally, NRPs function as virulence factors, such as siderophores and genotoxins [2]. Therefore, inhibiting their
Graphical Abstract
Figure 1: Biosynthesis of gramicidin S. Modules comprise the PCP, A, E, C, and TE domains. PCP, peptidyl carr...
Figure 2: (A) Adenylation reaction in a nonribosomal peptide synthetase. (B) Structures of aminoacyl-AMS inhi...
Figure 3: Illustration of the inhibition of A-domains by aminoacyl-AMS derivatives in live bacterial cells. C...
Scheme 1: Synthesis of 2′-OH-substituted ʟ-Phe-AMS derivatives. Reagents and conditions: (a) NaH, TBAI, R–X (...
Figure 4: Competitive labeling experiments of GrsA using probe 3 in the presence of ʟ-Phe-AMS inhibitors. (A)...
Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles
- Periklis X. Kolagkis,
- Eirini M. Galathri and
- Christoforos G. Kokotos
Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36
- -inflammatory, and even anticancer agents. Traditionally, the synthesis of BIMs has been achieved upon the acidic condensation of an aldehyde with indole, utilizing a variety of protic or Lewis acids. However, due to the increased environmental awareness of our society, the focus has shifted towards the
Graphical Abstract
Scheme 1: Examples of BIMs used for their medicinal properties.
Scheme 2: Mechanisms for the synthesis of BIMs using protic or Lewis acids as catalysts.
Scheme 3: Synthesis of bis(indolyl)methanes using DBDMH.
Scheme 4: Competition experiments and synthesis of bis(indolyl)methanes using DBDMH.
Scheme 5: Proposed mechanism for formation of BIM of using DBDMH.
Scheme 6: Synthesis of bis(indolyl)methanes using I2.
Scheme 7: General reaction mechanism upon halogen bonding.
Scheme 8: Synthesis of bis(indolyl)methanes using I2, introduced by Ji.
Scheme 9: Synthesis of bis(indolyl)methanes using Br2 in CH3CN.
Scheme 10: Βidentate halogen-bond donors.
Scheme 11: Synthesis of bis(indolyl)methanes using bidentate halogen-bond donor 26.
Scheme 12: Proposed reaction mechanism.
Scheme 13: Synthesis of bis(indolyl)methanes using iodoalkyne as catalyst.
Scheme 14: Proposed reaction mechanism.
Scheme 15: Optimized reaction conditions used by Ramshini.
Scheme 16: Activation of the carbonyl group by HPA/TPI-Fe3O4.
Scheme 17: Synthesis of BIMs in the presence of nanoAg-Pt/SiO2-doped silicate.
Scheme 18: Mechanism of action proposed by Khalafi-Nezhad et al.
Scheme 19: Activation of the carbonyl group by the Cu–isatin Schiff base complex.
Scheme 20: Optimum reaction conditions published by Jain.
Scheme 21: Organocatalytic protocol utilizing nanoparticles introduced by Bankar.
Scheme 22: Activation of the carbonyl group by the AlCl3·6H2O-SDS-SiO2 complex.
Scheme 23: Optimal reaction conditions for the aforementioned nano-Fe3O4 based catalysts.
Scheme 24: Nanocatalytic protocol proposed by Kaur et al.
Scheme 25: Microwave approach introduced by Yuan.
Scheme 26: Microwave approach introduced by Zahran et al.
Scheme 27: Microwave irradiation protocol introduced by Bindu.
Scheme 28: Silica-supported microwave irradiation protocol.
Scheme 29: Proposed mechanism for formation of BIM by Nongkhlaw.
Scheme 30: Microwave-assisted synthesis of BIMs catalyzed by succinic acid.
Scheme 31: Proposed mechanism of action of MMO-4.
Scheme 32: Catalytic approach introduced by Muhammadpoor-Baltork et al.
Scheme 33: Reaction conditions used by Xiao-Ming.
Scheme 34: Ultrasonic irradiation-based protocol published by Saeednia.
Scheme 35: Pyruvic acid-mediated synthesis of BIMs proposed by Thopate.
Scheme 36: Synthesis of BIMs using [bmim]BF4 or [bmim]PF6 ionic liquids.
Scheme 37: Synthesis of BIMs utilizing In(OTf)3 in octylmethylimidazolium hexafluorophosphate as ionic liquid.
Scheme 38: FeCl3·6H2O-catalyzed synthesis of BIMs with use of ionic liquid.
Scheme 39: Synthesis of BIMs utilizing the [hmim]HSO4/EtOH catalytic system.
Scheme 40: Synthesis of BIMs utilizing acidic ionic liquid immobilized on silica gel (ILIS-SO2Cl).
Scheme 41: The [bmim][MeSO4]-catalyzed reaction of indole with various aldehydes.
Scheme 42: The role of [bmim][MeSO4] in catalyzing the reaction of indole with aldehydes.
Scheme 43: Synthesis of BIMs utilizing FeCl3-based ionic liquid ([BTBAC]Cl-FeCl3) as catalyst.
Scheme 44: Synthesis of BIMs using [Msim]Cl at room temperature.
Scheme 45: [Et3NH][H2PO4]-catalyzed synthesis of bis(indolyl)methanes.
Scheme 46: PILs-catalyzed synthesis of bis(indolyl)methanes.
Scheme 47: FSILs-mediated synthesis of bis(indolyl)methanes.
Scheme 48: Possible “release and catch” catalytic process.
Scheme 49: Synthesis of bis(indolyl)methanes by [DABCO-H][HSO4].
Scheme 50: Synthesis of bis(indolyl)methanes by [(THA)(SO4)].
Scheme 51: Synthesis of BBSI-Cl and BBSI-HSO4.
Scheme 52: Synthesis of BIMs in the presence of BBSI-Cl and BBSI-HSO4.
Scheme 53: Chemoselectivity of the present method.
Scheme 54: Synthesis of BIMs catalyzed by chitosan-supported ionic liquid.
Scheme 55: Proposed mechanism of action of CSIL.
Scheme 56: Optimization of the reaction in DESs.
Scheme 57: Synthesis of BIMs using ChCl/SnCl2 as DES.
Scheme 58: Synthesis of BIMs derivatives in presence of DES.
Scheme 59: BIMs synthesis in choline chloride/urea (CC/U).
Scheme 60: Flow chemistry-based synthesis of BIMs by Ley.
Scheme 61: Flow chemistry-based synthesis of BIMs proposed by Nam et al.
Scheme 62: Amino-catalyzed reaction of indole with propionaldehyde.
Scheme 63: Aminocatalytic synthesis of BIMs.
Scheme 64: Proposed mechanism for the aminocatalytic synthesis of BIMs.
Scheme 65: Enzymatic reaction of indole with aldehydes.
Scheme 66: Proposed mechanism for the synthesis of BIMs catalyzed by TLIM.
Scheme 67: Proposed reaction mechanism by Badsara.
Scheme 68: Mechanism proposed by D’Auria.
Scheme 69: Photoinduced thiourea catalysis.
Scheme 70: Proposed mechanism of photoacid activation.
Scheme 71: Proposed mechanism of action for CF3SO2Na.
Scheme 72: Proposed mechanism for the synthesis of BIMs by Mandawad.
Scheme 73: Proposed mechanism for the (a) acid generation and (b) synthesis of BIMs.
Scheme 74: a) Reaction conditions employed by Khaksar and b) activation of the carbonyl group by HFIP.
Scheme 75: Activation of the carbonyl group by the PPy@CH2Br through the formation of a halogen bond.
Scheme 76: Reaction conditions utilized by Mhaldar et al.
Scheme 77: a) Reaction conditions employed by López and b) activation of the carbonyl group by thiourea.
Scheme 78: Infrared irradiation approach introduced by Luna-Mora and his research group.
Scheme 79: Synthesis of BIMs with the use of the Fe–Zn BMOF.
Photoinduced in situ generation of DNA-targeting ligands: DNA-binding and DNA-photodamaging properties of benzo[c]quinolizinium ions
- Julika Schlosser,
- Olga Fedorova,
- Yuri Fedorov and
- Heiko Ihmels
Beilstein J. Org. Chem. 2024, 20, 101–117, doi:10.3762/bjoc.20.11
- compounds, which have been employed in biomedical imaging and as potential DNA-targeting anticancer agents [14][15][16][17]. More recently, a benzoquinolizinium-based fluorescent dye was reported to be used as imaging agent for inflammation and for the evaluation of the physiological response to anti
Graphical Abstract
Scheme 1: Photoinduced formation of benzo[c]quinolizinium and its interaction with DNA upon intercalation.
Scheme 2: Synthesis of styrylpyridine derivatives 2a–g. Conditions: i: piperidine, MeOH, reflux (2a,c), ii: C...
Figure 1: Absorption spectra of styrylpyridine derivatives 2a (black), 2b (red), 2c (blue), 2d (green), 2e (m...
Figure 2: Changes of the absorption spectra during the irradiation of 2a in MeCN for 16 min (A), 2b in MeCN f...
Figure 3: Changes of the absorption spectra during the irradiation of 2c for 13 min (A), 2d for 12 min (B), 2e...
Scheme 3: Photoinduced formation of styrylpyridine derivatives 2b–g to the benzo[c]quinolizinium ions 3b–g (y...
Figure 4: Photometric titration of ct DNA to 3c (A) 3e (B) 3f (C) and 3g (D) (c = 20 µM) in Na phosphate buff...
Figure 5: Fluorimetric titration of ct DNA to 3c (A), 3e (B), 3f (C), and 3g (D) (c = 20 µM) in Na phosphate ...
Figure 6: CD (A) and LD (B) spectra of 3f and ct DNA (cDNA = 20 µM) in Na phosphate buffer (pH 7.0, T = 20 °C...
Figure 7: Changes of the absorption (A) and CD (B) spectra during the irradiation of 2e (1) and 2f (2) (c = 2...
Scheme 4: Proposed mechanisms for the photoinduced DNA damage initiated by photoexcitation of benzoquinolizin...
Synthesis of ether lipids: natural compounds and analogues
- Marco Antônio G. B. Gomes,
- Alicia Bauduin,
- Chloé Le Roux,
- Romain Fouinneteau,
- Wilfried Berthe,
- Mathieu Berchel,
- Hélène Couthon and
- Paul-Alain Jaffrès
Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96
Graphical Abstract
Figure 1: Chemical structure of some natural ether lipids (ELs).
Figure 2: Synthesis of lyso-PAF and PAF from 1-O-alkylglycerol [64].
Figure 3: Synthesis of lyso-PAF from 1,3-benzylideneglycerol 3.1 [69].
Figure 4: A) Synthesis of the two enantiomers of octadecylglycerol (4.6 and 4.10) from ᴅ-mannitol (4.1); B) s...
Figure 5: Four-step synthesis of PAF 5.6 from (S)-glycidol [73].
Figure 6: Synthesis of 1-O-alkylglycerol A) from solketal, B) from ᴅ- or ʟ-tartaric acid and the intermediate ...
Figure 7: Synthesis of EL building blocks starting from substituted glycidol 7.1a–c [82].
Figure 8: Synthesis of PAF 8.5 by using phosphoramidite 8.2 [86].
Figure 9: Synthesis of oleyl-PAF 9.7 from ʟ-serine [88].
Figure 10: Synthesis of racemic analogues of lyso-PAF 10.8 and PAF 10.9 featuring a phenyl group between the g...
Figure 11: Synthesis of racemic deoxy-lyso-PAF 11.7 and deoxy-PAF 11.8 [91].
Figure 12: Synthesis of racemic thio-PAF 12.8 [93].
Figure 13: Racemic synthesis of 13.6 to illustrate the modification of the glycerol backbone by adding a methy...
Figure 14: Racemic synthesis of 14.5 as an illustration of the introduction of methyl substituents on the glyc...
Figure 15: Synthesis of functionalized sn-2-acyl chains of PC-EL; A) Steglich esterification or acylation reac...
Figure 16: Synthesis of racemic mc-PAF (16.3), a carbamate analogue of PAF [102].
Figure 17: A) Synthesis of (R)-17.2 and (S)-17.6 starting from (S)-solketal (17.1); B) synthesis of N3-PAF (17...
Figure 18: Modification of the phosphocholine polar head to produce PAF analogues [81].
Figure 19: Racemic PAF analogues 19.3 and 19.5 characterized by the absence of the phosphate group [107].
Figure 20: Synthesis of PIP3-PAF (20.7) [108].
Figure 21: Large-scale synthesis of C18-edelfosine (21.8) [116].
Figure 22: Synthesis of C16-edelfosine (22.10) starting from isopropylidene-ʟ-glyceric acid methyl ester (22.1...
Figure 23: Phosphocholine moiety installation by the use of chlorophosphite 23.2 as key reagent [119].
Figure 24: Synthesis of rac-1-alkyl-2-O-methylglycerol (AMG) [120].
Figure 25: Synthesis of stereocontrolled 1-alkyl-2-O-methyl glycerol 25.9 (AMG) from dimethyl ᴅ-tartrate [81].
Figure 26: A) Racemic synthesis of thioether 26.4 [129,130], B) structure of sulfone analogue 26.5 [129].
Figure 27: Stereocontrolled synthesis of C18-edelfosine thioether analogue 27.8 [118].
Figure 28: Synthesis of thioether 28.4 that include a thiophosphate function [134].
Figure 29: Synthesis of ammonium thioether 29.4 and 29.6 [135].
Figure 30: Synthesis of the N-methylamino analogue of edelfosine 30.6 (BN52211) [138].
Figure 31: Synthesis of 1-desoxy analogues of edelfosine; A) with a saturated alkyl chain; B) synthesis of the...
Figure 32: Stereocontrolled synthesis of edelfosine analogue (S)-32.8 featuring a C18:1 lipid chain [142].
Figure 33: Synthesis of edelfosine analogues with modulation of the lipid chain; A) illustration with the synt...
Figure 34: Synthesis of phospholipid featuring a carbamate function to link the lipid chain to the glycerol un...
Figure 35: Synthesis of sesquiterpene conjugates of phospho glycero ether lipids [148].
Figure 36: Racemic synthesis of methyl-substituted glycerol analogues 36.7 and 36.10: A) synthesis of diether ...
Figure 37: Racemic synthesis of ilmofosine (37.6) [155,156].
Figure 38: A) Stereoselective synthesis of 38.5 via a stereoselective hydroboration reaction; B) synthesis of ...
Figure 39: Racemic synthesis of SRI62-834 (39.6) featuring a spiro-tetrahydrofurane heterocycle in position 2 ...
Figure 40: Racemic synthesis of edelfosine analogue 40.5 featuring an imidazole moiety in sn-2 position [160].
Figure 41: Racemic synthesis of fluorine-functionalized EL: A) Synthesis of 41.6 and B) synthesis of 41.8 [161-163].
Figure 42: A) Synthesis of the β-keto-ester 42.6 that also features a decyl linker between the phosphate and t...
Figure 43: Synthesis of phosphonate-based ether lipids; A) edelfosine phosphonate analogue 43.7 and B) thioeth...
Figure 44: Enantioselective synthesis of phosphonates 44.3 and 44.4 [171].
Figure 45: Racemic synthesis of phosphinate-based ether lipid 45.10 [172].
Figure 46: Racemic synthesis of edelfosine arsonium analogue 46.5 [173].
Figure 47: Synthesis of edelfosine dimethylammonium analogue 47.2 [118].
Figure 48: Synthesis of rac-C18-edelfosine methylammonium analogue 48.4 [176].
Figure 49: A) Synthesis of edelfosine N-methylpyrrolidinium analogue 49.2 or N-methylmorpholinium analogue 49.3...
Figure 50: A) Synthesis of edelfosine’s analogue 50.4 with a PE polar group; B) illustration of a pyridinium d...
Figure 51: A) Synthesis of 51.4 featuring a thiazolium cationic moiety; B) synthesis of thiazolium-based EL 51...
Figure 52: Synthesis of cationic ether lipids 52.3, 52.4 and 52.6 [135,183].
Figure 53: Synthesis of cationic carbamate ether lipid 53.5 [184].
Figure 54: Synthesis of cationic sulfonamide 54.5 [185].
Figure 55: Chemical structure of ONO-6240 (55.1) and SRI-63-119 (55.2).
Figure 56: Synthesis of non-ionic ether lipids 56.2–56.9 [188].
Figure 57: Synthesis of ether lipid conjugated to foscarnet 57.6 [189].
Figure 58: A) Synthesis of ether lipid conjugated to arabinofuranosylcytosine; B) synthesis of AZT conjugated ...
Figure 59: Synthesis of quercetin conjugate to edelfosine [191].
Figure 60: Synthesis of 60.8 (Glc-PAF) [194].
Figure 61: A) Synthesis of amino ether lipid 61.7 functionalized with a rhamnose unit and its amide analogue 6...
Figure 62: A) Synthesis of glucose ether lipid 62.4; B) structure of ether lipid 62.5 possessing a maltose uni...
Figure 63: A) Synthesis of glucuronic methyl ester 63.8; B) structure of cellobiose 63.9 and maltose 63.10 ana...
Figure 64: A) Synthesis of maltosyl glycerolipid 64.7; B) structure of lactose analogue 64.8 prepared followin...
Figure 65: A) Asymmetric synthesis of the aglycone moiety starting from allyl 4-methoxyphenyl ether; B) glycos...
Figure 66: A) Synthesis of ohmline possessing a lactose moiety. B) Structure of other glyco glycero lipids pre...
Figure 67: A) Synthesis of lactose-glycerol ether lipid 67.5; B) analogues possessing a maltose (67.6) or meli...
Figure 68: Synthesis of digalactosyl EL 68.6, A) by using trityl, benzyl and acetyl protecting groups, B) by u...
Figure 69: A) Synthesis of α-ohmline; B) structure of disaccharide ether lipids prepared by using similar meth...
Figure 70: Synthesis of lactose ether lipid 70.3 and its analogue 70.6 featuring a carbamate function as linke...
Figure 71: Synthesis of rhamnopyranoside diether 71.4 [196].
Figure 72: Synthesis of 1-O-hexadecyl-2-O-methyl-3-S-(α-ᴅ-1'-thioglucopyranosyl)-sn-glycerol (72.5) [225].
Figure 73: A) Preparation of lipid intermediate 73.4; B) synthesis of 2-desoxy-C-glycoside 73.10 [226].
Figure 74: Synthesis of galactose-pyridinium salt 74.3 [228].
Figure 75: Synthesis of myo-inositol derivative Ino-C2-PAF (75.10) [230].
Figure 76: A) Synthesis of myo-inositol phosphate building block 76.7; B) synthesis of myo-inositolphosphate d...
Figure 77: A) Synthesis of phosphatidyl-3-desoxy-inositol 77.4; B) synthesis of phosphono-3-desoxyinositol 77.9...
Figure 78: A) Structure of diether phosphatidyl-myo-inositol-3,4-diphosphate 78.1; B) synthesis of phosphatidy...
Figure 79: A) Synthesis of diether-phosphatidyl derivative 79.4 featuring a hydroxymethyl group in place of a ...
Figure 80: Synthesis of Glc-amine-PAF [78].
Figure 81: Synthesis of glucosamine ether lipid 81.4 and its analogues functionalized in position 3 of the ami...
Figure 82: Synthesis of fully deprotected aminoglucoside ether lipid 82.5 [246].
Figure 83: Synthesis of C-aminoglycoside 83.12 using Ramberg–Bäcklund rearrangement as a key step [250].
Figure 84: A) List of the most important glyco lipids and amino glyco lipids included in the study of Arthur a...
Figure 85: Synthesis of mannosamine ether lipid 85.6 [254].
Figure 86: A) Synthesis of glucosamine ether lipids with a non-natural ʟ-glucosamine moiety; B) synthesis of e...
Figure 87: A) Structure of the most efficient anticancer agents 87.1–87.4 featuring a diamino glyco ether lipi...
Figure 88: A) Synthesis of diamino glyco ether lipid 87.4; B) synthesis of bis-glycosylated ether lipid 88.10 [256]....
Figure 89: Synthesis of triamino ether lipid 89.4 [260].
Figure 90: Synthesis of chlorambucil conjugate 90.7 [261].
Figure 91: Three main methods for the preparation of glycerol ether lipid 91.3; A) from solketal and via a tri...
Figure 92: Four different methods for the installation of the phosphocholine polar head group; A) method using...
Figure 93: Illustration of two methods for the installation of saccharides or aminosaccharides; A) O-glycosyla...
Dipeptide analogues of fluorinated aminophosphonic acid sodium salts as moderate competitive inhibitors of cathepsin C
- Karolina Wątroba,
- Małgorzata Pawełczak and
- Marcin Kaźmierczak
Beilstein J. Org. Chem. 2023, 19, 434–439, doi:10.3762/bjoc.19.33
- , F, H, K, L, O, S, V, W, and X) [1]. Cathepsin C is considered a good target for designing new anticancer agents with broad substrate specificity [2]. Cathepsin C, which affects the processing of keratin, is of great importance in maintaining the structural organization of the epidermis, primarily
Graphical Abstract
Scheme 1: Synthetic strategy towards 5 and 7.
Scheme 2: Synthesis of 9 and 11. (a) R = -CH3; (b) R = -CH(CH3)2; (c) R = -CH2CH(CH3)2; (d) R = -CH(CH3)CH2CH3...
Figure 1: Dixon plot for the hydrolysis of Gly-Phe-pNA substrate catalyzed by bovine cathepsin C in the prese...
Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities
- Jorge de Lima Neto and
- Paulo Henrique Menezes
Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31
- , since Pettit and co-workers, in a program from U.S. National Cancer Institute for the discovery of new anticancer agents, initially showed that combretastatins D-1 (1) and D-2 (2) isolated from the bark of the Combretum caffrum tree inhibited the growth of the murine lymphocytic leukemia cell line P388
Graphical Abstract
Figure 1: Structures of some members of the combretastatin D series, corniculatolides, and isocorniculatolide...
Scheme 1: Biosynthetic pathway proposed by Pettit and co-workers.
Scheme 2: Biosynthetic pathway towards corniculatolides or isocorniculatolides proposed by Ponnapalli and co-...
Scheme 3: Retrosynthetic approaches.
Scheme 4: Attempt of total synthesis of 2 by Boger and co-workers employing the Mitsunobu approach [27].
Scheme 5: Total synthesis of combretastatin D-2 (2) reported by Boger and co-workers employing an intramolecu...
Scheme 6: Formal synthesis of combretastatin D-2 (2) by Deshpande and co-workers using the Mitsunobu conditio...
Scheme 7: Total synthesis of combretastatin D-2 (2) by Rychnovsky and Hwang [36].
Scheme 8: Divergent synthesis of (±)-1 form combretastatin D-2 (2) by Rychnovsky and Hwang [36].
Scheme 9: Enantioselective synthesis of 1 by Rychnovsky and Hwang employing Jacobsen catalyst [41].
Scheme 10: Synthesis of fragment 57 by Couladouros and co-workers [43,45].
Scheme 11: Formal synthesis of compound 2 by Couladouros and co-workers [43,45].
Scheme 12: Synthesis of fragment 66 by Couladouros and co-workers [44,45].
Scheme 13: Synthesis of fragment 70 by Couladouros and co-workers [44,45].
Scheme 14: Synthesis of fragment 77 by Couladouros and co-workers [44,45].
Scheme 15: Synthesis of combretastatins 1 and 2 by Couladouros and co-workers [44,45].
Scheme 16: Formal synthesis of compound 2 by Gangakhedkar and co-workers [48].
Scheme 17: Synthesis of fragment 14 by Cousin and co-workers [50].
Scheme 18: Synthesis of fragment 91 by Cousin and co-workers [50].
Scheme 19: Formal synthesis of compound 2 by Cousin and co-workers [50].
Scheme 20: Synthesis of 2 diolide by Cousin and co-workers [50].
Scheme 21: Synthesis of combretastatin D-4 (4) by Nishiyama and co-workers [54].
Scheme 22: Synthesis of fragment 112 by Pettit and co-workers [55].
Scheme 23: Synthesis of fragment 114 by Pettit and co-workers [55].
Scheme 24: Attempt to the synthesis of compound 2 by Pettit and co-workers [55].
Scheme 25: Synthesis of combretastatin-D2 (2) starting from isovanilin (80) by Pettit and co-workers [55].
Scheme 26: Attempted synthesis of combretastatin-D2 (2) derivatives through an SNAr approach [55].
Scheme 27: Synthesis of combretastatin D-4 (4) by Pettit and co-workers [55].
Scheme 28: Synthesis of combretastatin D-2 (2) by Harras and co-workers [57].
Scheme 29: Synthesis of combretastatin D-4 (4) by Harras and co-workers [57].
Scheme 30: Formal synthesis of combretastatin D-1 (1) by Harras and co-workers [57].
Scheme 31: Synthesis of 11-O-methylcorniculatolide A (5) by Raut and co-workers [69].
Scheme 32: Synthesis of isocorniculatolide A (7) and O-methylated isocorniculatolide A 8 by Raut and co-worker...
Scheme 33: Synthesis of isocorniculatolide B (10) and hydroxyisocorniculatolide B 175 by Kim and co-workers [71].
Scheme 34: Synthesis of compound 9, 178, and 11 by Kim and co-workers [71].
Scheme 35: Synthesis of combretastatin D-2 prodrug salts [55].
Figure 2: ED50 values of the combretastatin D family against murine P388 lymphocytic leukemia cell line (appr...
Figure 3: IC50 of compounds against α-glucosidase [19].
Synthesis of a new water-soluble hexacarboxylated tribenzotriquinacene derivative and its competitive host–guest interaction for drug delivery
- Man-Ping Li,
- Nan Yang and
- Wen-Rong Xu
Beilstein J. Org. Chem. 2022, 18, 539–548, doi:10.3762/bjoc.18.56
- larger cavity as compared to TBTQ-C6 due to the introduction of triazole rings. Two anticancer drug molecules, dimethyl viologen (MV) with a smaller size and DOX with a larger size, were selected as model anticancer agents for encapsulation by TBTQ-CB6 to form the host–guest complexes of TBTQ-CB6MV and
Graphical Abstract
Scheme 1: (a) Synthesis route to TBTQ-CB6. Conditions: (i) ethyl azidoacetate, CuSO4, sodium ascorbate, THF/H2...
Figure 1: (a) 1H NMR spectra (400 MHz, D2O, 25 °C) of (1) MV, (2) TBTQ-CB6 and MV, (3) TBTQ-CB6 with [TBTQ-CB6...
Figure 2: (a) 1H NMR spectra (400 MHz, D2O, 25 °C) of (1) DOX, (2) TBTQ-CB6 and DOX, (3) TBTQ-CB6 with [TBTQ-...
Figure 3: (a) 1H NMR spectra (400 MHz, D2O, 25 °C) and (b) partial magnified 1H NMR spectra of (1) SM, (2) TB...
Figure 4: (a) Fluorescence spectra of the mixture of TBTQ-CB6 and SM in different molar ratios at a constant ...
Figure 5: 1H NMR spectra (400 MHz, D2O, 25 °C) of (1) MV (3 mM), (2) TBTQ-CB6 and MV (3 mM each), (3–9) TBTQ-...
Figure 6: 1H NMR spectra (400 MHz, D2O, 25 °C) of (1) DOX (3 mM), (2) TBTQ-CB6 and DOX (3 mM each), (3–9) TBT...
Flow synthesis of oxadiazoles coupled with sequential in-line extraction and chromatography
- Kian Donnelly and
- Marcus Baumann
Beilstein J. Org. Chem. 2022, 18, 232–239, doi:10.3762/bjoc.18.27
- anticancer agents [21][22][23]. Previous reports of the synthesis of 1,3,4-oxadiazoles in continuous flow focused on the reaction between tetrazoles and carboxylic acids (Huisgen synthesis) [24][25]. Continuous flow technology has also been exploited for the further functionalisation of 1,3,4-oxadiazoles [26
Graphical Abstract
Scheme 1: Methods for accessing 1,3,4-oxadiazoles.
Scheme 2: Synthesis of acyl hydrazones 1a–j.
Scheme 3: Iodine-mediated cyclisation of hydrazones 1a–j yielding oxadiazoles 2a–j. Reaction conditions: 1a–j...
Scheme 4: Synthesis of complex oxadiazoles.
Scheme 5: Continuous flow scale-up reaction with in-line quench and extraction.
Scheme 6: Continuous flow setup equipped with in-line extraction and purification.
Efficient N-arylation of 4-chloroquinazolines en route to novel 4-anilinoquinazolines as potential anticancer agents
- Rodolfo H. V. Nishimura,
- Thiago dos Santos,
- Valter E. Murie,
- Luciana C. Furtado,
- Leticia V. Costa-Lotufo and
- Giuliano C. Clososki
Beilstein J. Org. Chem. 2021, 17, 2968–2975, doi:10.3762/bjoc.17.206
- -anilinoquinazoline; anticancer agents; N-arylation; 4-chloroquinazoline; microwave irradiation; Introduction N-Heterocyclic compounds are commonly present in pharmaceuticals, bioactive natural products, agrochemicals, and synthetic drugs [1][2]. Quinazoline, a benzo-fused N-heterocyclic framework (benzo-1,3-diazine
Graphical Abstract
Figure 1: Some antitumor agents containing the 4-anilinoquinazoline moiety.
Scheme 1: Examples of N-arylation reactions using 4-chloroquinazolines as substrates.
Scheme 2: Synthesis of verubulin analog.
Scheme 3: Synthesis of 4-chloro-6-halo-2-phenylquinazolines 8a and 8b. Conditions: a) NBS, CH3CN, 30 min, 25 ...
Scheme 4: N-Arylation reactions using ortho-, meta-, and para-substituted primary anilines of type 14 followe...
Scheme 5: N-Arylation reactions using 4-chloroquinazoline (16) and 4-chloro-2-methylquinazoline (17) to achie...
Synthesis of 1-indolyl-3,5,8-substituted γ-carbolines: one-pot solvent-free protocol and biological evaluation
- Premansh Dudhe,
- Mena Asha Krishnan,
- Kratika Yadav,
- Diptendu Roy,
- Krishnan Venkatasubbaiah,
- Biswarup Pathak and
- Venkatesh Chelvam
Beilstein J. Org. Chem. 2021, 17, 1453–1463, doi:10.3762/bjoc.17.101
- single-photon counting (TCSPC) experiments. The average fluorescence lifetime of compound 3ac was found to be 8.35 ns and 4.73 ns in DMSO and DCM, respectively (Table 2, Figure 4). Biological evaluation of γ-carbolines as anticancer agents A panel of carboline derivatives 3ac, 3bc, 3ca, and 3ga, along
Graphical Abstract
Figure 1: Selected examples of compounds containing the γ-carboline core.
Scheme 1: The synthetic strategy of present work in comparison with previous reports.
Scheme 2: Series of synthesized 1-indolyl-3,5,8-substituted γ-carboline 3aa–ac, 3ba-ea and 1-indolyl-1,2-dihy...
Figure 2: Single-crystal XRD structure of 3ac (CCDC: 1897787).
Scheme 3: Plausible mechanism for the formation of 1,2-dihydro-γ-carboline derivative 3ga and 1-indolyl-3,5,8...
Figure 3: UV–vis absorption (left side) and emission (right side) spectra of 3ac measured in different solven...
Figure 4: Fluorescence decay profile of 3ac in DMSO (left side; λex 360 nm) and 10−5 M solutions of compound ...
Figure 5: Dose–response curves for (A) γ-carbolines 3ac, 3bc, 3ca, 3ga in the breast cancer cell line, MCF7 a...
Figure 6: Dose–response curve of γ-carbolines 3ac, 3bc, 3ca, 3ga in macrophage cell line, RAW264.7.
Figure 7: Laser scanning confocal microscopy studies (λex = 405 nm; collection range = 420–470 nm) for uptake...
Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects
- Shivani Gulati,
- Stephy Elza John and
- Nagula Shankaraiah
Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71
- -alkylated pyridones are valuable scaffolds offering biological activity such as immunomodulators, memory-enhancers and anticancer agents [109][110]. A direct approach to achieve N-alkylated pyridones are less explored and those available present limitations such as poor selectivity and yields, expensive
Graphical Abstract
Figure 1: Marketed drugs with acridine moiety.
Scheme 1: Synthesis of 4-arylacridinediones.
Scheme 2: Proposed mechanism for acridinedione synthesis.
Scheme 3: Synthesis of tetrahydrodibenzoacridinones.
Scheme 4: Synthesis of naphthoacridines.
Scheme 5: Plausible mechanism for naphthoacridines.
Figure 2: Benzoazepines based potent molecules.
Scheme 6: Synthesis of azepinone.
Scheme 7: Proposed mechanism for azepinone formation.
Scheme 8: Synthesis of benzoazulenen-1-one derivatives.
Scheme 9: Proposed mechanism for benzoazulene-1-one synthesis.
Figure 3: Indole-containing pharmacologically active molecules.
Scheme 10: Synthesis of functionalized indoles.
Scheme 11: Plausible mechanism for the synthesis of functionalized indoles.
Scheme 12: Synthesis of spirooxindoles.
Scheme 13: Synthesis of substituted spirooxindoles.
Scheme 14: Plausible mechanism for the synthesis of substituted spirooxindoles.
Scheme 15: Synthesis of pyrrolidinyl spirooxindoles.
Scheme 16: Proposed mechanism for pyrrolidinyl spirooxindoles.
Figure 4: Pyran-containing biologically active molecules.
Scheme 17: Synthesis of functionalized benzopyrans.
Scheme 18: Plausible mechanism for synthesis of benzopyran.
Scheme 19: Synthesis of indoline-spiro-fused pyran derivatives.
Scheme 20: Proposed mechanism for indoline-spiro-fused pyran.
Scheme 21: Synthesis of substituted naphthopyrans.
Figure 5: Marketed drugs with pyrrole ring.
Scheme 22: Synthesis of tetra-substituted pyrroles.
Scheme 23: Mechanism for silica-supported PPA-SiO2-catalyzed pyrrole synthesis.
Scheme 24: Synthesis of pyrrolo[1,10]-phenanthrolines.
Scheme 25: Proposed mechanism for pyrrolo[1,10]-phenanthrolines.
Figure 6: Marketed drugs and molecules containing pyrimidine and pyrimidinones skeletons.
Scheme 26: MWA-MCR pyrimidinone synthesis.
Scheme 27: Two proposed mechanisms for pyrimidinone synthesis.
Scheme 28: MWA multicomponent synthesis of dihydropyrimidinones.
Scheme 29: Proposed mechanism for dihydropyrimidinones.
Figure 7: Biologically active fused pyrimidines.
Scheme 30: MWA- MCR for the synthesis of pyrrolo[2,3-d]pyrimidines.
Scheme 31: Proposed mechanism for pyrrolo[2,3-d]pyrimidines.
Scheme 32: Synthesis of substituted pyrrolo[2,3-d]pyrimidine-2,4-diones.
Scheme 33: Probable pathway for pyrrolo[2,3-d]pyrimidine-2,4-diones.
Scheme 34: Synthesis of pyridopyrimidines.
Scheme 35: Plausible mechanism for the synthesis of pyridopyrimidines.
Scheme 36: Synthesis of dihydropyridopyrimidine and dihydropyrazolopyridine.
Scheme 37: Proposed mechanism for the formation of dihydropyridopyrimidine.
Scheme 38: Synthesis of thiopyrano[4,3-d]pyrimidines.
Scheme 39: Plausible mechanism for the synthesis of thiopyrano[4,3-d]pyrimidines.
Scheme 40: Synthesis of decorated imidazopyrimidines.
Scheme 41: Proposed mechanism for imidazopyrimidine synthesis.
Figure 8: Pharmacologically active molecules containing purine bases.
Scheme 42: Synthesis of aza-adenines.
Scheme 43: Synthesis of 5-aza-7-deazapurines.
Scheme 44: Proposed mechanism for deazapurines synthesis.
Figure 9: Biologically active molecules containing pyridine moiety.
Scheme 45: Synthesis of steroidal pyridines.
Scheme 46: Proposed mechanism for steroidal pyridine.
Scheme 47: Synthesis of N-alkylated 2-pyridones.
Scheme 48: Two possible mechanisms for pyridone synthesis.
Scheme 49: Synthesis of pyridone derivatives.
Scheme 50: Postulated mechanism for synthesis of pyridone.
Figure 10: Biologically active fused pyridines.
Scheme 51: Benzimidazole-imidazo[1,2-a]pyridines synthesis.
Scheme 52: Mechanism for the synthesis of benzimidazole-imidazo[1,2-a]pyridines.
Scheme 53: Synthesis of pyrazolo[3,4-b]pyridine-5-spirocycloalkanedione derivatives.
Scheme 54: Proposed mechanism for spiro-pyridines.
Scheme 55: Functionalized macrocyclane-fused pyrazolo[3,4-b]pyridine derivatives.
Scheme 56: Mechanism postulated for macrocyclane-fused pyrazolo[3,4-b]pyridine.
Scheme 57: Generation of pyrazolo[3,4-b]pyridines.
Scheme 58: Proposed mechanism for the synthesis of pyrazolo[3,4-b]pyridines.
Scheme 59: Proposed mechanism for the synthesis of azepinoindole.
Figure 11: Pharmaceutically important molecules with quinoline moiety.
Scheme 60: Povarov-mediated quinoline synthesis.
Scheme 61: Proposed mechanism for Povarov reaction.
Scheme 62: Synthesis of pyrazoloquinoline.
Scheme 63: Plausible mechanism for pyrazoloquinoline synthesis.
Figure 12: Quinazolinones as pharmacologically significant scaffolds.
Scheme 64: Four-component reaction for dihydroquinazolinone.
Scheme 65: Proposed mechanism for dihydroquinazolinones.
Scheme 66: Synthesis purine quinazolinone and PI3K-δ inhibitor.
Scheme 67: Synthesis of fused benzothiazolo/benzoimidazoloquinazolinones.
Scheme 68: Proposed mechanism for fused benzothiazolo/benzoimidazoloquinazolinones.
Scheme 69: On-water reaction for synthesis of thiazoloquinazolinone.
Scheme 70: Proposed mechanism for the thiazoloquinazolinone synthesis.
Scheme 71: β-Cyclodextrin-mediated synthesis of indoloquinazolinediones.
Scheme 72: Proposed mechanism for synthesis of indoloquinazolinediones.
Figure 13: Triazoles-containing marketted drugs and pharmacologically active molecules.
Scheme 73: Cu(I) DAPTA-catalyzed 1,2,3-triazole formation.
Scheme 74: Mechanism for Cu(I) DAPTA-catalyzed triazole formation.
Scheme 75: Synthesis of β-hydroxy-1,2,3-triazole.
Scheme 76: Proposed mechanism for synthesis of β-hydroxy-1,2,3-triazoles.
Scheme 77: Synthesis of bis-1,2,4-triazoles.
Scheme 78: Proposed mechanism for bis-1,2,4-triazoles synthesis.
Figure 14: Thiazole containing drugs.
Scheme 79: Synthesis of a substituted thiazole ring.
Scheme 80: Synthesis of pyrazolothiazoles.
Figure 15: Chromene containing drugs.
Scheme 81: Magnetic nanocatalyst-mediated aminochromene synthesis.
Scheme 82: Proposed mechanism for the synthesis of chromenes.
Amino- and polyaminophthalazin-1(2H)-ones: synthesis, coordination properties, and biological activity
- Zbigniew Malinowski,
- Emilia Fornal,
- Agata Sumara,
- Renata Kontek,
- Karol Bukowski,
- Beata Pasternak,
- Dariusz Sroczyński,
- Joachim Kusz,
- Magdalena Małecka and
- Monika Nowak
Beilstein J. Org. Chem. 2021, 17, 558–568, doi:10.3762/bjoc.17.50
- coordination compounds with Cu(II) ions. The results of biological tests showed that the compounds containing an amino- or polyamino-substituent at the 4-position of the phthalazinone moiety could have potential applications as new anticancer agents. Structure of biologically active phthalazine derivatives
Graphical Abstract
Figure 1: Structure of biologically active phthalazine derivatives.
Scheme 1: Synthetic route to aminophthalazinones 5 and 6.
Figure 2: Proposed catalytic cycles for the amination of 4-bromophthalazinones of type 3 (Phthal: phthalazino...
Scheme 2: Synthesis of 4-amino- and 4-polyaminophthalazinones 5 and 6 (the yields refer to the isolated compo...
Figure 3: The phthalazinone derivatives that were used to test the complexation of Cu(II) ions.
Scheme 3: The proposal of the fragmentation pathway of the Cu(II) complex with compound 7.
Figure 4: Structure of complex 17.
Figure 5: Molecular structure of complex 17 with atom numbering scheme. The anisotropic displacement paramete...
Figure 6: Determination of relative cell viability (% of control) in different cell lines (HT-29; PC-3 and L-...
Figure 7: Cytotoxic properties of the phthalazinone derivatives expressed as IC50 after 72 h of cell treatmen...
Synthesis and properties of quinazoline-based versatile exciplex-forming compounds
- Rasa Keruckiene,
- Simona Vekteryte,
- Ervinas Urbonas,
- Matas Guzauskas,
- Eigirdas Skuodis,
- Dmytro Volyniuk and
- Juozas V. Grazulevicius
Beilstein J. Org. Chem. 2020, 16, 1142–1153, doi:10.3762/bjoc.16.101
- , such as monitoring of specific biological activities and as antimalarial and anticancer agents [5][6]. However, electroactive properties of derivatives of this acceptor have been scarcely reported. Quinazoline-based compounds were used as hosts for red phosphorescent OLEDs with an external quantum
Graphical Abstract
Scheme 1: Synthesis of quinazoline derivatives 1–3. Conditions: i) ammonium acetate, copper(II) chloride, iso...
Figure 1: DSC (a, b, c) and TGA (d) curves of compounds 1–3. Scan rates were 20 °C/min (TGA) and 10 °C/min (D...
Figure 2: Frontier-orbital distributions and optimized geometries at the ground state of quinazoline-based co...
Figure 3: Cyclic voltammograms of quinazoline-based compounds 1–3.
Figure 4: UV–vis absorption spectra of compounds 1–3. a) Theoretical and b) experimental spectra of compounds ...
Figure 5: Fluorescence spectra (a) of dilute solutions and thin films of compounds 1–3 (λexc = 350 nm and PL ...
Figure 6: Electron and hole NTOs of compounds 1–3 in the S1 excited state (vacuum).
Figure 7: Chemical structures of exciplex-forming materials used, and visualization of white electroluminesce...
Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules
- Valerian Dragutan,
- Ileana Dragutan,
- Albert Demonceau and
- Lionel Delaude
Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68
- . Securinega alkaloids The total synthesis of the Securinega alkaloids, (−)-flueggine A (18) and (+)-virosaine B (19), which are potent anticancer agents, was proposed by Wei et al. [90] via a relay ring-closing metathesis (RRCM) associated with a 1,3-dipolar cycloaddition. The enyne precursors bearing a
Graphical Abstract
Scheme 1: Intramolecular (A) and intermolecular (B) enyne metathesis reactions.
Scheme 2: Ene–yne and yne–ene mechanisms for intramolecular enyne metathesis reactions.
Scheme 3: Metallacarbene mechanism in intermolecular enyne metathesis.
Scheme 4: The Oguri strategy for accessing artemisinin analogs 1a–c through enyne metathesis.
Scheme 5: Access to the tetracyclic core of nanolobatolide (2) via tandem enyne metathesis followed by an Eu(...
Scheme 6: Synthesis of (−)-amphidinolide E (3) using an intermolecular enyne metathesis as the key step.
Scheme 7: Synthesis of amphidinolide K (4) by an enyne metathesis route.
Scheme 8: Trost synthesis of des-epoxy-amphidinolide N (5) [72].
Scheme 9: Enyne metathesis between the propargylic derivative and the allylic alcohol in the synthesis of the...
Scheme 10: Synthetic route to amphidinolide N (6a).
Scheme 11: Synthesis of the stereoisomeric precursors of amphidinolide V (7a and 7b) through alkyne ring-closi...
Scheme 12: Synthesis of the anthramycin precursor 8 from ʟ-methionine by a tandem enyne metathesis–cross metat...
Scheme 13: Synthesis of (−)‐clavukerin A (9) and (−)‐isoclavukerin A (10) by an enyne metathesis route startin...
Scheme 14: Synthesis of (−)-isoguaiene (11) through an enyne metathesis as the key step.
Scheme 15: Synthesis of erogorgiaene (12) by a tandem enyne metathesis/cross metathesis sequence using the sec...
Scheme 16: Synthesis of (−)-galanthamine (13) from isovanilin by an enyne metathesis.
Scheme 17: Application of enyne metathesis for the synthesis of kempene diterpenes 14a–c.
Scheme 18: Synthesis of the alkaloid (+)-lycoflexine (15) through enyne metathesis.
Scheme 19: Synthesis of the AB subunits of manzamine A (16a) and E (16b) by enyne metathesis.
Scheme 20: Jung's synthesis of rhodexin A (17) by enyne metathesis/cross metathesis reactions.
Scheme 21: Total synthesis of (−)-flueggine A (18) and (+)-virosaine B (19) from Weinreb amide by enyne metath...
Scheme 22: Access to virgidivarine (20) and virgiboidine (21) by an enyne metathesis route.
Scheme 23: Enyne metathesis approach to (−)-zenkequinone B (22).
Scheme 24: Access to C-aryl glycoside 23 by an intermolecular enyne metathesis/Diels–Alder cycloaddition.
Scheme 25: Synthesis of spiro-C-aryl glycoside 24 by a tandem intramolecular enyne metathesis/Diels–Alder reac...
Scheme 26: Pathways to (−)-exiguolide (25) by Trost’s Ru-catalyzed enyne cross-coupling and cross-metathesis [94].
Rapid, two-pot procedure for the synthesis of dihydropyridinones; total synthesis of aza-goniothalamin
- Thomas J. Cogswell,
- Craig S. Donald and
- Rodolfo Marquez
Beilstein J. Org. Chem. 2020, 16, 135–139, doi:10.3762/bjoc.16.15
- cell line, Figure 1). Thus, a path for the generation of a new class of potential anticancer agents based on the aza-goniothalamin framework was determined [17][18]. Results and Discussion Our approach to the synthesis of the dihydropyridinone framework was inspired by the work carried out by Veenstra
Graphical Abstract
Figure 1: Aza-goniothalamin 1, (R)-(+)-goniothalamin 2 and acylated aza-goniothalamin analogue 3 [14-18].
Scheme 1: One pot synthesis of benzyl carbamate 4 reported by Veenstra and co-workers [19].
Scheme 2: Formation of diene 5 in 66% through a one pot, three component coupling.
Scheme 3: Optimized conditions for the synthesis of diene 5.
Scheme 4: Ring-closing metathesis reaction of diene 5 to yield dihydropyridone 7 [20-23].
Figure 2: Extension of the two-pot methodology to include a variety of different aldehyde starting materials.
Scheme 5: Total synthesis of aza-goniothalamin 1.
α,ß-Didehydrosuberoylanilide hydroxamic acid (DDSAHA) as precursor and possible analogue of the anticancer drug SAHA
- Shital K. Chattopadhyay,
- Subhankar Ghosh,
- Sarita Sarkar and
- Kakali Bhadra
Beilstein J. Org. Chem. 2019, 15, 2524–2533, doi:10.3762/bjoc.15.245
- sorting) The results were further complimented with ROS dependent cytotoxicity in the above cell line. ROS generation, induced by various anticancer agents plays a key role in apoptosis [37]. Cells were treated with SAHA, 11b, 11f and 11g at GI25, GI50 and GI75 concentrations for 24 h and analyzed in the
Graphical Abstract
Figure 1: Some hydroxamic acid-based anti-tumor drugs.
Scheme 1: Synthesis of SAHA and DDSAHA.
Figure 2: Cell viability from MTT assay for SAHA, 11b, 11f and 11g on HeLa after 24 h treatment.
Figure 3: Percent of cell death by LDH assay at a GI50 dose of SAHA, 11b, 11f and 11g after 24 h incubation a...
Figure 4: ROS generation by DCFDA.
Figure 5: The quantitative results of bivariate FITC-Annexin V/PI FCM of HeLa cells after treatment with 11b ...
Figure 6: Fluorescence microscopic images of 11b at different concentrations (8.9, and 14.2 µM, respectively)...
Figure 7: DNA Ladder formation in a gel electrophoresis study of 11b at different concentrations (at 8.9, and...
Current understanding and biotechnological application of the bacterial diterpene synthase CotB2
- Ronja Driller,
- Daniel Garbe,
- Norbert Mehlmer,
- Monika Fuchs,
- Keren Raz,
- Dan Thomas Major,
- Thomas Brück and
- Bernhard Loll
Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228
- isolated in 1985 from cigarette smoke condensate and identified as anticancer agents [76]. With quite similar potency (α-CBT: 25.2 µM and β-CBT: 21.9 µM [77]), they showed inhibition of the induction of Epstein–Barr virus early antigen by lymphoblastoid cancer cells. In the tobacco plant itself, both
Graphical Abstract
Figure 1: CotB1 synthesizes geranylgeranyl diphosphate (GGDP) 3 from the substrates dimethylallyl diphosphate...
Figure 2: The bacterial diterpene synthase CotB2wt·Mg2+3·F-Dola in the closed, active conformation (PDB-ID 6G...
Figure 3: Conformational changes of CotB2 upon ligand binding. Superposition of CotB2’s open (teal), pre-cata...
Figure 4: View into the active site of CotB2wt·Mg2+3·F-Dola [37] superimposed with CotB2wt·Mg2+B·GGSDP [36]. (A) The ...
Figure 5: View into the active site of CotB2wt·Mg2+3·F-Dola [37]. Identical view as in Figure 4. (A) The bound F-Dola rea...
Figure 6: The WXXXXXRY motif in protein sequences of diterpene TPS from different bacteria. Highlighted is th...
Scheme 1: Overview of the altered product portfolio as a result of introduced point mutations in the active s...
Scheme 2: Catalytic mechanism of CotB2, derived from isotope labeling experiments [34,35], density functional theory...
Figure 7: (A) The inner surface of the active site is shown in gray. The bound F-Dola reaction intermediate i...
Scheme 3: Variants of CotB2 open the route to a novel product portfolio with altered cyclic carbon skeletons,...
Heck- and Suzuki-coupling approaches to novel hydroquinone inhibitors of calcium ATPase
- Robert J. Kempton,
- Taylor A. Kidd-Kautz,
- Soizic Laurenceau and
- Stefan Paula
Beilstein J. Org. Chem. 2019, 15, 971–975, doi:10.3762/bjoc.15.94
- sarcoplasmic reticulum (SR) within muscle cells. It transfers Ca2+ from the cytosol to the lumen of the SR at the expense of ATP hydrolysis. Specific inhibitors of SERCA are of significance to human health because of their well-documented value as research tools and their potential as novel anticancer agents
Graphical Abstract
Figure 1: Thapsigargin- and hydroquinone-based SERCA inhibitors.
Scheme 1: Friedel–Crafts alkylation of 4.
Scheme 2: Heck cross-coupling reactions.
Scheme 3: Suzuki approach to a tethered hydroquinone.
Photochemical generation of the 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) radical from caged nitroxides by near-infrared two-photon irradiation and its cytocidal effect on lung cancer cells
- Ayato Yamada,
- Manabu Abe,
- Yoshinobu Nishimura,
- Shoji Ishizaka,
- Masashi Namba,
- Taku Nakashima,
- Kiyofumi Shimoji and
- Noboru Hattori
Beilstein J. Org. Chem. 2019, 15, 863–873, doi:10.3762/bjoc.15.84
- for 2b in benzene. The cytocidal effect of compound 2a on lung cancer cells under photolysis conditions was also assessed to test the efficacy as anticancer agents. In a medium containing 100 μg mL−1 of 2a exposed to light, the number of living cells decreased significantly compared to the unexposed
- strong DNA-damaging activity [65], they play important roles as anticancer therapeutic agents [66]. Among the free radicals, nitroxides including the TEMPO radical have unique properties, where they can act not only as radical scavengers, but also as anticancer agents [67]. Due to the unique properties
Graphical Abstract
Scheme 1: Photochemical generation of TEMPO radical.
Scheme 2: Synthesis of caged nitroxides 2a and 2b.
Figure 1: Photochemical generation of TEMPO from 2a and 2b. EPR spectra acquired during the photolysis of 2a ...
Figure 2: Time profile for photochemical generation of TEMPO radical from 2 (5 mM) at ≈298 K in benzene: (a) ...
Scheme 3: Photochemical generation of TEMPO radical and photoproducts 6 and 7 under air atmosphere.
Figure 3: Time profile, ln([2a]/[2a]0) versus irradiation time, of two-photon uncaging reaction of TEMPO in t...
Figure 4: ESR spectra acquired during the photolysis of 2a (5 mM) in benzene using 365 nm light.
Scheme 4: Isodesmic reaction from BRa and 5b to 5a and BRb.
Figure 5: Irradiation time-dependent decline in viability of LLC cells with compound 2a.
Figure 6: Detection of intracellular ROS only in irradiated LLC cells with 2a-containing medium.
A chemoenzymatic synthesis of ceramide trafficking inhibitor HPA-12
- Seema V. Kanojia,
- Sucheta Chatterjee,
- Subrata Chattopadhyay and
- Dibakar Goswami
Beilstein J. Org. Chem. 2019, 15, 490–496, doi:10.3762/bjoc.15.42
- and inexpensive synthesis of HPA-12 was felt. Our own interest in developing anticancer agents also prompted us to develop a new and practical enantioselective synthesis of 2 [26][27][28][29]. To realize our objective, we paid particular attention to obtain 2 using reactions that are high-yielding and
Graphical Abstract
Figure 1: Structure of most active HPA-12 isomers, originally proposed (1) and revised (2).
Scheme 1: Lipase-catalyzed trans-acylation of (±)-4 and subsequent Mitsunobu inversion. Conditions: (i) Zn/TH...
Scheme 2: Synthesis of azide 9 from (S)-4. Conditions: (i) NaH/Bu4NI/BnBr/THF/25 °C/4 h; (ii) AD-mix-β/t-BuOH...
Scheme 3: Attempted synthesis of 2 from 9. Conditions: (i) (a) LiAlH4 (1 M in THF)/THF/25 °C/3 h, (b) DCC/DMA...
Scheme 4: Actual synthesis of 2 from 9. Conditions: (i) DDQ/CH2Cl2–H2O 4:1/3 h; (ii) a) LiAlH4/THF/25 °C/3 h,...
Study on the regioselectivity of the N-ethylation reaction of N-benzyl-4-oxo-1,4-dihydroquinoline-3-carboxamide
- Pedro N. Batalha,
- Luana da S. M. Forezi,
- Maria Clara R. Freitas,
- Nathalia M. de C. Tolentino,
- Ednilsom Orestes,
- José Walkimar de M. Carneiro,
- Fernanda da C. S. Boechat and
- Maria Cecília B. V. de Souza
Beilstein J. Org. Chem. 2019, 15, 388–400, doi:10.3762/bjoc.15.35
- mentioned above, we have been putting some effort on synthesizing different 4-oxoquinoline-3-carboxamide derivatives as potential anticancer agents [13]. The synthesis of such derivatives have been planned considering that, once having obtained the 4-oxo-1,4-dihydroquinoline-3-carboxamide scaffold
Graphical Abstract
Figure 1: Structures of some bioactive 4-oxoquinoline-3-carboxamide derivatives 1–4 with different bioactive ...
Figure 2: Structural modifications on the 4-oxo-1,4-dihydroquinoline-3-carboxamide scaffold.
Scheme 1: Synthetic route for the preparation of 1-ethyl-4-oxoquinoline-3-carboxamide 7.
Scheme 2: Reaction steps and main transition state leading to compound 7.
Figure 3: Same scale partial 1H NMR spectra of compounds 5 and 7 (DMSO-d6, 500 MHz).
Figure 4: 1H,1H-COSY spectrum of derivative 7 (DMSO-d6, 500 MHz).
Figure 5: Partial HMBC spectrum of derivative 7 (DMSO-d6, 500 MHz).
Figure 6: Asymmetric unit of product 7.
Scheme 3: Deprotonation of 5 forming 8a and 8b, followed by reaction with bromoethane leading to products 7 a...
Scheme 4: Acid–base equilibria considered for the data displayed in Table 2.
Scheme 5: Charge dispersion due to resonance effects for both deprotonated species.
Synthesis of nonracemic hydroxyglutamic acids
- Dorota G. Piotrowska,
- Iwona E. Głowacka,
- Andrzej E. Wróblewski and
- Liwia Lubowiecka
Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22
- ]. Several derivatives of L-glutamic acid functioning as anticancer agents have been reported [4]. But primarily L-glutamic acid is known as the major excitatory neurotransmitter in central nervous system which acts by binding to glutamate receptors [5][6][7]. However, these interactions are linked to
Graphical Abstract
Figure 1: Structure of L-glutamic acid.
Figure 2: 3-Hydroxy- (2), 4-hydroxy- (3) and 3,4-dihydroxyglutamic acids (4).
Figure 3: Enantiomers of 3-hydroxyglutamic acid (2).
Scheme 1: Synthesis of (2S,3R)-2 from (R)-Garner's aldehyde. Reagents and conditions: a) MeOCH=CH–CH(OTMS)=CH2...
Scheme 2: Synthesis of (2S,3R)-2 and (2S,3S)-2 from (R)-Garner’s aldehyde. Reagents and conditions: a) H2C=CH...
Scheme 3: Two-carbon homologation of the protected L-serine. Reagents and conditions: a) Fmoc-succinimide, Na2...
Scheme 4: Synthesis of di-tert-butyl ester of (2R,3S)-2 from L-serine. Reagents and conditions: a) PhSO2Cl, K2...
Scheme 5: Synthesis of (2R,3S)-2 from O-benzyl-L-serine. Reagents and conditions: a) (CF3CH2O)2P(O)CH2COOMe, ...
Scheme 6: Synthesis of (2S,3R)-2 employing a one-pot cis-olefination–conjugate addition sequence. Reagents an...
Scheme 7: Synthesis of the orthogonally protected (2S,3R)-2 from a chiral aziridine. Reagents and conditions:...
Scheme 8: Synthesis of N-Boc-protected (2S,3R)-2 from D-phenylglycine. Reagents and conditions: a) BnMgCl, et...
Scheme 9: Synthesis of (2S,3R)-2 employing ketopinic acid as chiral auxiliary. Reagents and conditions: a) Br2...
Scheme 10: Synthesis of dimethyl ester of (2S,3R)-2 employing (1S)-2-exo-methoxyethoxyapocamphane-1-carboxylic...
Scheme 11: Synthesis of N-Boc-protected dimethyl ester of (2S,3R)-2 from (S)-N-(1-phenylethyl)thioacetamide. R...
Scheme 12: Synthesis of N-Boc-protected dimethyl ester of (2S,3R)-2 via Sharpless epoxidation. Reagents and co...
Scheme 13: Synthesis of (2S,3S)-2 from the imide 51. Reagents and conditions: a) NaBH4, MeOH/CH2Cl2; b) Ac2O, ...
Scheme 14: Synthesis of (2R,3S)-2 and (2S,3S)-2 from the acetolactam 55 (PMB = p-methoxybenzyl). Reagents and ...
Scheme 15: Synthesis of (2S,3R)-2 from D-glucose. Reagents and conditions: a) NaClO2, 30% H2O2, NaH2PO4, MeCN;...
Figure 4: Enantiomers of 3-hydroxyglutamic acid (3).
Scheme 16: Synthesis of (4S)-4-hydroxy-L-glutamic acid [(2S,4S)-3] by electrophilic hydroxylation. Reagents an...
Scheme 17: Synthesis of all stereoisomers of 4-hydroxyglutamic acid (3). Reagents and conditions: a) Br2, PBr5...
Scheme 18: Synthesis of the orthogonally protected 4-hydroxyglutamic acid (2S,4S)-73. Reagents and conditions:...
Scheme 19: Synthesis of (2S,4R)-4-acetyloxyglutamic acid as a component of a dipeptide. Reagents and condition...
Scheme 20: Synthesis of N-Boc-protected dimethyl esters of (2S,4R)- and (2S,4S)-3 from (2S,4R)-4-hydroxyprolin...
Scheme 21: Synthesis of orthogonally protected (2S,4S)-3 from (2S,4R)-4-hydroxyproline. Reagents and condition...
Scheme 22: Synthesis of the protected (4R)-4-hydroxy-L-pyroglutamic acid (2S,4R)-87 by electrophilic hydroxyla...
Figure 5: Enantiomers of 3,4-dihydroxy-L-glutamic acid (4).
Scheme 23: Synthesis of (2S,3S,4R)-4 from the epoxypyrrolidinone 88. Reagents and conditions: a) MeOH, THF, KC...
Scheme 24: Synthesis of (2S,3R,4R)-4 from the orthoester 92. Reagents and conditions: a) OsO4, NMO, acetone/wa...
Scheme 25: Synthesis of (2S,3S,4S)-4 from the aziridinolactone 95. Reagents and conditions: a) BnOH, BF3·OEt2,...
Scheme 26: Synthesis of (2S,3S,4R)-4 and (2R,3S,4R)-4 from cyclic imides 106. Reagents and conditions: a) NaBH4...
Scheme 27: Synthesis of (2R,3R,4R)-4 and (2S,3R,4R)-4 from the cyclic meso-imide 110. Reagents and conditions:...
Scheme 28: Synthesis of (2S,3S,4S)-4 from the protected serinal (R)-23. Reagents and conditions: a) Ph3P=CHCOO...
Scheme 29: Synthesis of (2S,3S,4S)-4 from O-benzyl-N-Boc-D-serine. Reagents and conditions: a) ClCOOiBu, TEA, ...
Scheme 30: Synthesis of (2S,3S,4R)-127 by enantioselective conjugate addition and asymmetric dihydroxylation. ...
Figure 6: Structures of selected compounds containing hydroxyglutamic motives (in blue).
Regioselective addition of Grignard reagents to N-acylpyrazinium salts: synthesis of substituted 1,2-dihydropyrazines and Δ5-2-oxopiperazines
- Valentine R. St. Hilaire,
- William E. Hopkins,
- Yenteeo S. Miller,
- Srinivasa R. Dandepally and
- Alfred L. Williams
Beilstein J. Org. Chem. 2019, 15, 72–78, doi:10.3762/bjoc.15.8
- ; Introduction Pyrazine and piperazine ring systems are key structural elements in a large number of biologically active molecules [1][2][3][4][5][6]. Compounds containing these scaffolds were shown to behave as anticancer agents [2][3][4][5], sodium channel blockers [5], and also display antiviral activity [7
Graphical Abstract
Figure 1: Regioselective addition of Grignard reagents to mono- and disubstituted pyrazinium salts (yields re...
Assembly of fully substituted triazolochromenes via a novel multicomponent reaction or mechanochemical synthesis
- Robby Vroemans,
- Yenthel Verhaegen,
- My Tran Thi Dieu and
- Wim Dehaen
Beilstein J. Org. Chem. 2018, 14, 2689–2697, doi:10.3762/bjoc.14.246
- and 5e furnishes piperazin-1-ylchromene 12 in 64% yield. Furthermore, as highly methylated flavonoid derivatives [47] and 6-(3,5-dimethoxyphenyl)chromenes [48][49] have been demonstrated to be potent anti-seizure drugs and anticancer agents, respectively, a Suzuki–Miyaura reaction was performed
Graphical Abstract
Scheme 1: Two-step reaction towards triazolochromene 5a and obtained oxidized side product 6.
Scheme 2: Reaction pathways leading to the different regioisomers.
Figure 1: Scope with respect to various salicylaldehydes 1a–f, nitroalkenes 2a–d and organic azides 4a–g. aRe...
Scheme 3: Synthesis of bis-chromenotriazole 5p.
Figure 2: Generality of products obtained via the two-pot mechanochemical procedure, varying the salicylaldeh...
Scheme 4: Scale-up of the one-pot three-component reaction and two-step ball milling procedure.
Scheme 5: Postfunctional transformations of triazolochromenes.
Microwave-assisted synthesis of biologically relevant steroidal 17-exo-pyrazol-5'-ones from a norpregnene precursor by a side-chain elongation/heterocyclization sequence
- Gergő Mótyán,
- László Mérai,
- Márton Attila Kiss,
- Zsuzsanna Schelz,
- Izabella Sinka,
- István Zupkó and
- Éva Frank
Beilstein J. Org. Chem. 2018, 14, 2589–2596, doi:10.3762/bjoc.14.236
- . This indicates that the pyrazolone heterocyclic ring at the 17β position is a promising scaffold for the design of anticancer agents of the Δ5 androstene series. 1H NMR spectra of compound 7f in CDCl3 (top; # solvent signal) and in DMSO-d6 (bottom; # solvent signal). Multistep synthesis of steroidal β
Graphical Abstract
Scheme 1: Multistep synthesis of steroidal β-ketoesters 4 and 4' from pregnenolone acetate (1) and pregnadien...
Scheme 2: Cyclization of compound 4 with hydrazine hydrate (5a), phenylhydrazine (5b) and methylhydrazine (5c...
Figure 1: 1H NMR spectra of compound 7f in CDCl3 (top; # solvent signal) and in DMSO-d6 (bottom; # solvent si...
