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Search for "anticancer drugs" in Full Text gives 54 result(s) in Beilstein Journal of Organic Chemistry.
Multicomponent synthesis of artificial nucleases and their RNase and DNase activity
- Anton V. Gulevich,
- Lyudmila S. Koroleva,
- Olga V. Morozova,
- Valentina N. Bakhvalova,
- Vladimir N. Silnikov and
- Valentine G. Nenajdenko
Beilstein J. Org. Chem. 2011, 7, 1135–1140, doi:10.3762/bjoc.7.131
- anticancer drugs [2][3] and new therapeutics against RNA-containing viruses. Recently, a number of synthetic RNA-cleaving molecules (artificial ribonucleases) had been developed and tested in vitro [4][5][6][7][8][9][10][11]. Among numerous artificial ribonucleases, peptidomimetics showed evident advantages
Graphical Abstract
Figure 1: Novel artificial RNases based on amino acids.
Scheme 1: Multicomponent approach to target molecules.
Scheme 2: Synthesis of starting diisocyanides 3a–3e.
Scheme 3: Synthesis of new aRNAses. Conditions: a. RCHO (3 eqiuv), BnNH2 (3 equiv), PhP(OH)2 (1 equiv), r.t.;...
Figure 2: Results of RT-qPCR of the TBEV RNA cleavage products in presence of 2.5 mM peptidomimetics 5a–g at ...
Figure 3: Results of RT-qPCR of the TBEV RNA cleavage products in the presence of 2.5 mM peptidomimetics afte...
Figure 4: Results of electrophoresis in 2% TBE-agarose gel with ethidium bromide of RT-qPCR products from Figure 3. (...
Synthesis, reactivity and biological activity of 5-alkoxymethyluracil analogues
- Lucie Brulikova and
- Jan Hlavac
Beilstein J. Org. Chem. 2011, 7, 678–698, doi:10.3762/bjoc.7.80
- instance, was one of the first [1] and most investigated anticancer drugs, either chemically or biologically, and triggered the research of 5-substituted pyrimidine analogues. The elucidation of the life cycle of a virus is crucial in antiviral chemotherapy. Several 5-substituted pyrimidine analogues
Graphical Abstract
Figure 1: Investigated derivatives.
Figure 2: Modifications of uracil ring.
Figure 3: 5-(3,3,3-Trifluoro-1-methoxypropyl)-2'-deoxyuridine (1).
Scheme 1: Synthesis of 5-(3,3,3-trifluoro-1-methoxypropyl)-2'-deoxyuridine (1) and 5-(3,3,3-trifluoro-1-(2-pr...
Scheme 2: Synthesis of 5-(3,3,3-trifluoro-1-methoxyprop-1-yl)-5,6-dihydro-2'-deoxyuridine (8).
Scheme 3: Synthesis of 5-(methoxy-2-haloethyl)-2'-deoxyuridines 12 and 13.
Scheme 4: Synthesis of 5-(1-methoxy-2-iodoethyl) nucleosides 28–30.
Figure 4: [125I] radiolabelled 5-(1-methoxy-2-iodoethyl)-2'-deoxyuridine 31.
Scheme 5: Synthesis of 5-(1-alkoxy-2-iodoethyl) 34–36 and 5-(1-ethoxy-2,2-diiodoethyl)-2'-deoxyuridine (33).
Scheme 6: Synthesis of 5-(1-methoxy-2-iodoethyl)-3',5'-di-O-acetyl-2'-deoxyuridine (38) and 5-(1-ethoxy-2-iod...
Figure 5: 5-(1-Hydroxy(or ethoxy)-2-haloethyl)-3',5'-di-O-acetyl-2'-deoxyuridines 43–46.
Scheme 7: 5-(1-Methoxy-2,2-dihaloethyl)-2'-deoxyuridines 47–49.
Scheme 8: Synthesis of 5-[1-(2-haloethyl(or nitro)ethoxy)-2-iodoethyl]-2'-deoxyuridines 50–54.
Scheme 9: Synthesis of alkoxyuracil analogues 56–61.
Figure 6: 5-(Methoxy-2-haloethyl)uracils 62–64.
Scheme 10: Synthesis of perfluoro derivatives 70–74.
Scheme 11: Synthesis of 1-β-D-arabinofuranosyl-5-(1-methoxy-2-iodoethyl)uracil (79).
Scheme 12: Synthesis of 1-β-D-arabinofuranosyl-5-(2,2-dibromo-1-methoxyethyl)uracil 82 and uridine analogue 83....
Scheme 13: Synthesis of methoxy derivative 87.
Scheme 14: Synthesis of 5-(1-methoxy-2-azidoethyl)-2'-deoxyuridine (93).
Scheme 15: Synthesis of methoxyalkyl derivatives 96 and 97.
Scheme 16: Synthesis of 5-(1-methoxyethyl)-2'-deoxyuridine (100).
Scheme 17: Synthesis of 2'-deoxy-5-(1-methoxyethyl)-4'-thiouridine (104).
Figure 7: 5-(1-Butoxyethyl)uracil 105 and 5-(1-butoxyethyl)-2'-deoxyuridine (106).
Scheme 18: Synthesis of β- and α-anomer of 5-(1-ethoxy-2-methylprop-1-yl)-2'-deoxyuridine.
Scheme 19: Synthesis of 5-(1-acyloxyethyl)-1-(tetrahydrofuran-2-yl)uracils 117 and 118.
Scheme 20: Synthesis of 5-(1,2-diacetoxyethyl)-3',5'-di-O-acetyl-2'-deoxyuridine 120.
Scheme 21: Synthesis of 5-[alkoxy-(4-nitrophenyl)methyl]uracils 124.
Scheme 22: Synthesis of 5-[alkoxy-(4-nitrophenyl)methyl]uridines 126 and 127.
Scheme 23: Synthesis of phosphoramidite 134. Reaction conditions 1: (a) TBDMSCl, imidazole, pyridine, 33 h, 99...
Scheme 24: Synthesis of phosphoramidite 145. (a) B(OCH3)3, CH(OCH3)3, Na2CO3, MeOH, 150 °C; (b) I2, (0.6 equiv...
Figure 8: Oligonucleotide 146.
Scheme 25: Synthesis of phosphoramidite 150.
Figure 9: 2'-Deoxyuridine derivatives 151–154.
Scheme 26: Synthesis of 2'-deoxyuridine derivatives 151–152.
Scheme 27: Synthesis of 5-[3-(2'-deoxyuridin-5-yl)-1-methoxyprop-1-yl]-2'-deoxyuridine (163).
Scheme 28: Synthesis of “metallocenonucleosides” 164 and 167.
Scheme 29: Synthesis of 5-(2,4:3,5-di-O-benzylidene-D-pentahydroxypentyl)-2,4-di-tert-butoxy-pyrimidine 172 an...
Figure 10: α- and β-pseudouridine (174 and 175).
Figure 11: 5'-Modified pseudouridine 176 and secopseudouridines 177, 178.
Figure 12: Methoxy derivatives 12, 13 and 28.
Figure 13: 5-(1-Methoxy-2,2-dihaloethyl)-2'-deoxyuridines 47–49.
Figure 14: 5-(1-Methoxyethyl)-2'-deoxyuridine 100.
Figure 15: 2'-Deoxy-5-(1-methoxyethyl)-4'-thiouridine (104).
Figure 16: 5-(1-Methoxy-2-azidoethyl)-2'-deoxyuridine (93).
Figure 17: 5-[1-(2-Halo(or nitro)ethoxy-2-iodoethyl)]-2'-deoxyuridines 50–54.
Figure 18: 5-[Alkoxy-(4-nitrophenyl)-methyl] uracil analogues 124, 126 and 127.
Figure 19: Methoxyiodoethyl pyrimidine nucleoside 79.
Figure 20: 5-[alkoxy-(4-nitro-phenyl)-methyl]uridines 126 and 127.
Mitomycins syntheses: a recent update
- Jean-Christophe Andrez
Beilstein J. Org. Chem. 2009, 5, No. 33, doi:10.3762/bjoc.5.33
- ), D-glucosamine 21 and carbamoyl phosphate (Scheme 4) [29][30][31][32]. The key intermediate, AHBA, is also a common precursor to other anticancer drugs, such as rifamycin and ansamycin. 2.2. Mode of action Mitomycins are quinone antitumor antibiotics that exert their biological activity through DNA
Graphical Abstract
Scheme 1: Aziridine containing natural products.
Scheme 2: Mitomycin structures and nomenclature.
Scheme 3: Base catalysed epimerization of mitomycin B.
Scheme 4: Biosynthesis of mitomycin C (MMC) 7.
Scheme 5: Mode of action of mitomycin C.
Scheme 6: The N–C3–C9a disconnection.
Scheme 7: Danishefsky’s Retrosynthesis of mitomycin K.
Scheme 8: Hetero Diels–Alder reaction en route to mitomycins.
Scheme 9: Nitroso Diels–Alder cycloaddition.
Scheme 10: Frank azide cycloadddition.
Scheme 11: Final steps of mitomycin K synthesis. aPDC, DCM; bPhSCH2N3, PhH, 80 °C; cL-selectride, THF, −78 °C; ...
Scheme 12: Naruta–Maruyama retrosynthesis.
Scheme 13: Synthesis of a leucoaziridinomitosane by nitrene cycloaddition. aAlCl3-Et2O; bNaH, ClCH2OMe; cn-BuL...
Scheme 14: Thermal decomposition of azidoquinone 51.
Scheme 15: Diastereoselectivity during the cycloaddition.
Scheme 16: Oxidation with iodo-azide.
Scheme 17: Williams’ approach towards mitomycins.aDEIPSCl, Imidazole, DCM; bPd/C, HCO2NH4, MeOH; cAllocCl, NaH...
Scheme 18: Synthesis of pyrrolidones by homoconjugate addition.
Scheme 19: Homoconjugate addition on the fully functionalized substrate.
Scheme 20: Introduction of the olefin.
Scheme 21: Retrosynthesis of N–C9a, N–C3 bond formation.
Scheme 22: Synthesis of the pyrrolo[1,2]indole 82 using N-PSP activation.aAc2O, Py; bAc2O, Hg(OAc)2, AcOH, 90%...
Scheme 23: Synthesis of an aziridinomitosane. am-CPBA, DCM then iPr2NH, CCl4 reflux; bK2CO3, MeOH; cBnBr, KH; d...
Scheme 24: Oxidation products of a leucoaziridinomitosane obtained from a Polonovski oxidation.
Scheme 25: Polonovski oxidation of an aziridinomitosane. am-CPBA; bPd/C, H2; cDimethoxypropane, PPTS.
Scheme 26: The C1–C9a disconnection.
Scheme 27: Ziegler synthesis of desmethoxymitomycin A.aIm2C=O, THF; bNH3; cTMSOTf, 2,6-di-tert-butylpyridine, ...
Scheme 28: Transformation of sodium erythorbate.aTBDMSCl; bNaN3; cPPh3; d(Boc)2O, DMAP; eTBAF; fTf2O, Pyr.
Scheme 29: Formation of C9,C10-unsaturation in the mitomycins. am-CPBA, DCM; bO3, MeOH; cMe2S; dKHMDS, (EtO)3P...
Scheme 30: Fragmentation mechanism.
Scheme 31: Michael addition-cyclisation.
Scheme 32: SmI2 8-endo-dig cyclisation.
Scheme 33: Synthesis of pyrrolo[1,2-a]indole by 5-exo-dig radical cyclization.
Scheme 34: The C9–C9a disconnection.
Scheme 35: Intramolecular nitrile oxide cycloaddition.
Scheme 36: Regioselectivity of the INOC.
Scheme 37: Fukuyama’s INOC strategy.
Scheme 38: Synthesis of a mitosane core by rearrangement of a 1-(1-pyrrolidinyl)-1,3-butadiene.
Scheme 39: Sulikowski synthesis of an aziridinomitosene. aPd(Tol3P)2Cl2, Bu3SnF, 140; bH2, Pd/C; cTFAA, Et3N; d...
Scheme 40: Enantioselective carbene insertion.
Scheme 41: Parson’s radical cyclization.
Scheme 42: Cha’s mitomycin B core synthesis.
Scheme 43: The N-aromatic disconnection.
Scheme 44: Kishi retrosynthesis.
Scheme 45: Kishi synthesis of a starting material. aallyl bromide, K2CO3, acetone, reflux; bN,N-Dimethylanilin...
Scheme 46: Kishi synthesis of MMC 7. aLDA, THF, −78 °C then PhSeBr, THF, −78 °C; bH2O2, THF-EtOAc; cDIBAL, DCM...
Scheme 47: Acid catalyzed degradation of MMC 7.
Scheme 48: In vivo formation of apomitomycin B.
Scheme 49: Advanced intermediate for apomitomycin B synthesis.
Scheme 50: Remers synthesis of a functionalized mitosene. aTMSCl, Et3N, ZnCl2 then NBS; bAcOK; cNH2OH; dPd/C, H...
Scheme 51: Coleman synthesis of desmethoxymitomycin A. aSnCl2, PhSH, Et3N, CH3CN; bClCO2Bn, Et3N; cPPh3, DIAD,...
Scheme 52: Transition state and pyrrolidine synthesis.
Scheme 53: Air oxidation of mitosanes and aziridinomitosanes.
Scheme 54: The C9-aromatic disconnection.
Scheme 55: Synthesis of the aziridine precursor. aLHMDS, THF; bNaOH; c(s)-α-Me-BnNH2, DCC, HOBT; dDIBAL; eK2CO3...
Scheme 56: Synthesis of 206 via enamine conjugate addition.
Scheme 57: Rapoport synthesis of an aziridinomitosene.
Scheme 58: One pot synthesis of a mitomycin analog.
Scheme 59: Synthesis of compound 218 via intramolecular Heck coupling. aEtMgCl, THF, then 220; bMsCl, Et3N; cN...
Scheme 60: Elaboration of indole 223. aEt3N, Ac2O; bAcOH; cSOCl2, Et3N; dNaN3, DMF; eH2SO4, THF; fK2CO3, MeOH; ...
Scheme 61: C9-C9a functionalization from indole.
Scheme 62: Synthesis of mitomycin K. a2 equiv. MoO5.HMPA, MeOH; bPPh3, Et3N, THF-H2O; cMeOTf, Py, DCM; dMe3SiCH...
Scheme 63: Configurational stability of mitomycin K derivatives.
Scheme 64: Epimerization of carbon C9a in compound 227b.
Scheme 65: Corey–Chaykovsky synthesis of indol 235.
Scheme 66: Cory intramolecular aza-Darzens reaction for the formation of aziridinomitosene 239.
Scheme 67: Jimenez synthesis of aziridinomitosene 242.
Scheme 68: Von Braun opening of indoline 244.
Scheme 69: C9a oxidation of an aziridinomitosane with DDQ/OsO4.
Scheme 70: Synthesis of epi-mitomycin K. aNaH, Me2SO4; bH2, Pd/C; cMitscher reagent [165]; d[(trimethylsilyl)methyl...
Scheme 71: Mitomycins rearrangement.
Scheme 72: Fukuyama’s retrosynthesis.
Scheme 73: [2+3] Cycloaddition en route to isomitomycin A. aToluene, 110 °C; bDIBAL, THF, −78 °C; cAc2O, Py.; d...
Scheme 74: Final steps of Fukuyama’s synthesis.
Scheme 75: “Crisscross annulation”.
Scheme 76: Synthesis of 274; the 8-membered ring 274 was made using a crisscross annulation. a20% Pd(OH)2/C, H2...
Scheme 77: Conformational analysis of compound 273 and 275.
Scheme 78: Synthesis of a mitomycin analog. aNa2S2O4, H2O, DCM; bBnBr (10 equiv), K2CO3, 18-crown-6 (cat.), TH...
Scheme 79: Vedejs retrosynthesis.
Scheme 80: Formation of the azomethine ylide.
Scheme 81: Vedejs second synthesis of an aziridinomitosene. aDIBAL; bTPAP, NMO; c287; dTBSCl, imidazole.
Scheme 82: Trityl deprotection and new aziridine protecting group 300.
Scheme 83: Ene reaction towards benzazocinones.
Scheme 84: Benzazocenols via homo-Brook rearrangement.
Scheme 85: Pt-catalyzed [3+2] cycloaddition.
Scheme 86: Carbonylative lactamization entry to benzazocenols. aZn(OTf)2, (+)-N-methylephedrine, Et3N, TMS-ace...
Scheme 87: 8 membered ring formation by RCM. aBOC2O, NaHCO3; bTBSCl, Imidazole, DMF; callyl bromide, NaH, DMF; ...
Scheme 88: Aziridinomitosene synthesis. aTMSN3; bTFA; cPOCl3, DMF; dNaClO2, NaH2PO4, 2-methyl-2-butene; eMeI, ...
Scheme 89: Metathesis from an indole.
Scheme 90: Synthesis of early biosynthetic intermediates of mitomycins.
Reduction of arenediazonium salts by tetrakis(dimethylamino)ethylene (TDAE): Efficient formation of products derived from aryl radicals
- Mohan Mahesh,
- John A. Murphy,
- Franck LeStrat and
- Hans Peter Wessel
Beilstein J. Org. Chem. 2009, 5, No. 1, doi:10.3762/bjoc.5.1
- 1.5 equivalents of TDAE in anhydrous DMF yielded the indoles 51b–d in 63%, 43% and 64% yields (in three steps from the corresponding aryl amines 48b–d) respectively (Scheme 7). The indole 51d bearing a fused 9-membered ring was of particular interest to us because the important anticancer drugs
Graphical Abstract
Scheme 1: Aza- and thia-substituted electron donors.
Scheme 2: Radical-polar crossover reaction of arenediazonium salts by TTF.
Scheme 3: Studies on the reductive radical cyclization of arenediazonium salt 16 by TDAE.
Scheme 4: Preparation of the arenediazonium salts 31a–d. Reagents and conditions: (a) 23, NaH, THF, 0 °C, 0.5...
Scheme 5: Cascade radical cyclizations of arenediazonium salts 42 and 44 by TDAE. Reagents and conditions: (a...
Scheme 6: TDAE-mediated radical based addition-elimination route to indoles.
Scheme 7: Cyclization of the arenediazonium salts 49b–d by TDAE. Reagents and conditions: (a) NOBF4, CH2Cl2, ...
Scheme 8: Cyclization of the arenediazonium salt 62 by TDAE. Reagents and conditions: (a) 2-Nitrobenzenesulfo...
Scheme 9: Mechanism for the formation of the tetracyclic sulfonamide 65.
Scheme 10: Possible mechanism for the formation of indole (63) and indole sulfonamide 64.
