PDF herunterladen
Synlett 2019; 30(02): 161-166
DOI: 10.1055/s-0037-1610352
letter
© Georg Thieme Verlag Stuttgart · New York

10-Membered Azaenediyne Fused to a Benzothiophene through the Nicholas Macrocyclization: Synthesis and DNA Cleavage Ability

Natalia A. Danilkina
a   Institute of Chemistry, Saint Petersburg State University (SPbSU), Universitetskaya nab. 7/9, 199034 Saint Petersburg, Russia   eMail: i.balova@spbu.ru
,
Andrey M. Rumyantsev
b   Department of Genetics and Biotechnology, Saint Petersburg State University (SPbSU), Universitetskaya nab. 7/9, 199034 Saint Petersburg, Russia
,
Anna L. Lyapunova
a   Institute of Chemistry, Saint Petersburg State University (SPbSU), Universitetskaya nab. 7/9, 199034 Saint Petersburg, Russia   eMail: i.balova@spbu.ru
,
Alexander S. D’yachenko
a   Institute of Chemistry, Saint Petersburg State University (SPbSU), Universitetskaya nab. 7/9, 199034 Saint Petersburg, Russia   eMail: i.balova@spbu.ru
,
Alexander F. Khlebnikov 
a   Institute of Chemistry, Saint Petersburg State University (SPbSU), Universitetskaya nab. 7/9, 199034 Saint Petersburg, Russia   eMail: i.balova@spbu.ru
,
Irina A. Balova  *
a   Institute of Chemistry, Saint Petersburg State University (SPbSU), Universitetskaya nab. 7/9, 199034 Saint Petersburg, Russia   eMail: i.balova@spbu.ru
› InstitutsangabenThis study was supported by Saint Petersburg State University (SPbU) (grant numbers 12.40.537.2017 and 12.40.515.2017) and by RFBR grants: 17-03-00910 (synthesis of enediyne 1, kinetic studies, and bioactivity studies) and 18-33-01265 (synthesis of O-enediyne 2 and C-enediyne 3 for bioactivity studies).
Weitere Informationen

Publikationsverlauf

Received: 04. November 2018

Accepted after revision: 13. November 2018

Publikationsdatum:
11. Dezember 2018 (online)

    Lizenzen und Reprints Alle Artikel dieser Rubrik


Abstract

The Nicholas-type macrocyclization through NH-tosyl functional group has been found to be an efficient technique for the synthesis of a 10-membered azaenediyne system annulated with a benzothiophene. To compare the activity of azaenediyne synthesized with similar oxa- and carbocyclic enediynes the Bergman cyclization activation energies and the ability of enediynes to cleave DNA (pBR322 plasmid) were investigated. The order of reactivity predicted by DFT calculations (N-enediyne < C-enediyne < O-enediyne) was confirmed by DSC analysis data. Surprisingly azaenediyne was found to be more active in the DNA cleavage assay than the C-analogue.

Key words

Nicholas reaction - Bergman cyclization - iodocyclization - enediyne - alkyne - benzothiophene - pBR322 plasmid

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0037-1610352.
  • Supporting Information
 

  • References and Notes

  • 1 Nicholas KM, Pettit R. J. Organomet. Chem. 1972; 44: C21
    CrossrefSuche in Google Scholar
  • 2 Connor RE, Nicholas KM. J. Organomet. Chem. 1977; 125: C45
    CrossrefSuche in Google Scholar
  • 3 Green JR. Curr. Org. Chem. 2001; 5: 809
    CrossrefSuche in Google Scholar
  • 4 Teobald BJ. Tetrahedron 2002; 58: 4133
    CrossrefSuche in Google Scholar
  • 5 Nicholas KM. J. Org. Chem. 2015; 80: 6943
    CrossrefPubMedSuche in Google Scholar
  • 6 Bavetsias V, Henderson EA, McDonald E. Tetrahedron 2007; 63: 1537
    CrossrefSuche in Google Scholar
  • 7 Henderson EA, Bavetsias V, Theti DS, Wilson SC, Clauss R, Jackman AL. Bioorg. Med. Chem. 2006; 14: 5020
    CrossrefPubMedSuche in Google Scholar
  • 8 Amin J, Motevalli M, Richards CJ. J. Organomet. Chem. 2015; 776: 43
    CrossrefSuche in Google Scholar
  • 9 Wells SM, Widen JC, Harki DA, Brummond KM. Org. Lett. 2016; 18: 4566
    CrossrefPubMedSuche in Google Scholar
  • 10 Closser KD, Quintal MM, Shea KM. J. Org. Chem. 2009; 74: 3680
    CrossrefPubMedSuche in Google Scholar
  • 11 Kaneda K, Naruse R, Yamamoto S. Org. Lett. 2017; 19: 1096
    CrossrefPubMedSuche in Google Scholar
  • 12 Kaneda K, Fujita M, Naruse R. Heterocycles 2016; 92: 291
    CrossrefSuche in Google Scholar
  • 13 Asamizu T, Naruse R, Yongxue G, Kaneda K. Tetrahedron Lett. 2015; 56: 4674
    CrossrefSuche in Google Scholar
  • 14 Christie SD. R, Davoile RJ, Jones RC. F. Org. Biomol. Chem. 2006; 4: 2683
    CrossrefPubMedSuche in Google Scholar
  • 15 Akimura N, Fujii A, Kamada F, Nogiwa R, Yamamoto S, Sato T, Ishikawa S, Okazaki T, Kaneda K. Synthesis 2016; 48: 3931
    Thieme ConnectSuche in Google Scholar
  • 16 Hernández JN, Ramírez MA, Rodríguez ML, Martín VS. Org. Lett. 2008; 10: 2349
    CrossrefPubMedSuche in Google Scholar
  • 17 Grammatoglou K, Bolsakova J, Jirgensons A. RSC Adv. 2017; 7: 27530
    CrossrefSuche in Google Scholar
  • 18 Igawa K, Aoyama S, Kawasaki Y, Kashiwagi T, Seto Y, Ni R, Mitsuda N, Tomooka K. Synlett 2017; 28: 2110
    Thieme ConnectSuche in Google Scholar
  • 19 Carrillo R, Martín T, López-Rodríguez M, Crisóstomo FP. Org. Lett. 2014; 16: 552
    CrossrefPubMedSuche in Google Scholar
  • 20 Ni R, Mitsuda N, Kashiwagi T, Igawa K, Tomooka K. Angew. Chem. Int. Ed. 2015; 54: 1190
    CrossrefPubMedSuche in Google Scholar
  • 21 Hagendorn T, Braese S. RSC Adv. 2014; 4: 15493
    CrossrefSuche in Google Scholar
  • 22 Prudhomme M. In Anticancer Agents from Natural Products, Second Edition . Gordon M, Cragg DG. I, Kingston DJ. N. CRC Press; Boca Raton, FL: 2011: 647
    CrossrefSuche in Google Scholar
  • 23 Kar M, Basak A. Chem. Rev. 2007; 107: 2861
    CrossrefPubMedSuche in Google Scholar
  • 24 Basak A, Roy S, Roy B, Basak A. Curr. Top. Med. Chem. 2008; 8: 487
    CrossrefPubMedSuche in Google Scholar
  • 25 Klein M, Walenzyk T, König B. Collect. Czech. Chem. Commun. 2004; 69: 945
    CrossrefSuche in Google Scholar
  • 26 Basak A, Mandal S, Bag SS. Chem. Rev. 2003; 103: 4077
    CrossrefPubMedSuche in Google Scholar
  • 27 Bhattacharya P, Basak A, Campbell A, Alabugin IV. Mol. Pharmaceutics 2018; 15: 768
    CrossrefPubMedSuche in Google Scholar
  • 28 Shain JC, Khamrai UK, Basak A. Tetrahedron Lett. 1997; 38: 6067
    CrossrefSuche in Google Scholar
  • 29 Basak A, Mandal S, Das AK, Bertolasi V. Bioorg. Med. Chem. Lett. 2002; 12: 873
    CrossrefPubMedSuche in Google Scholar
  • 30 Hatial I, Jana S, Bisai S, Das M, Ghosh AK, Anoop A, Basak A. RSC Adv. 2014; 4: 28041
    CrossrefSuche in Google Scholar
  • 31 Basak A, Kar M. Bioorg. Med. Chem. 2008; 16: 4532
    CrossrefPubMedSuche in Google Scholar
  • 32 Du Y, Creighton CJ, Yan Z, Gauthier DA, Dahl JP, Zhao B, Belkowski SM, Reitz AB. Bioorg. Med. Chem. 2005; 13: 5936
    CrossrefPubMedSuche in Google Scholar
  • 33 Poloukhtine A, Popik VV. J. Am. Chem. Soc. 2007; 129: 12062
    CrossrefPubMedSuche in Google Scholar
  • 34 Dutta S, Basak A, Dasgupta S. Bioorg. Med. Chem. 2009; 17: 3900
    CrossrefPubMedSuche in Google Scholar
  • 35 Hatial I, Addy PS, Ghosh AK, Basak A. Tetrahedron Lett. 2013; 54: 854
    CrossrefSuche in Google Scholar
  • 36 Kaiser J, Esseveldt BC. J, van Segers MJ. A, Delft FL, van Smits JM. M, Butterworth S, Rutjes FP. J. T. Org. Biomol. Chem. 2009; 7: 695
    CrossrefPubMedSuche in Google Scholar
  • 37 Magnus P. Tetrahedron 1994; 50: 1397
    CrossrefSuche in Google Scholar
  • 38 Roy S, Anoop A, Biradha K, Basak A. Angew. Chem. Int. Ed. 2011; 50: 8316
    CrossrefPubMedSuche in Google Scholar
  • 39 Roy B, Basak A. Synlett 2006; 2804
    Thieme Connect
  • 40 Basak A, Shain JC, Khamrai UK, Rudra KR, Basak A. J. Chem. Soc., Perkin Trans. 1 2000; 1955
  • 41 Banfi L, Guanti G. Eur. J. Org. Chem. 1998; 1543
  • 42 Roy SK, Basak A. Chem. Commun. 2006; 1646
    PubMed
  • 43 Lyapunova AG, Danilkina NA, Rumyantsev AM, Khlebnikov AF, Chislov MV, Starova GL, Sambuk EV, Govdi AI, Bräse S, Balova IA. J. Org. Chem. 2018; 83: 2788
    CrossrefPubMedSuche in Google Scholar
  • 44 Lyapunova AG, Danilkina NA, Khlebnikov AF, Köberle B, Bräse S, Balova IA. Eur. J. Org. Chem. 2016; 4842
  • 45 Kulyashova AE, Ponomarev AV, Selivanov SI, Khlebnikov AF, Popik VV, Balova IA. Arabian J. Chem. 2018; 11
    CrossrefSuche in Google Scholar
  • 46 Danilkina N, Nieger M, Selivanov S, Brase S, Balova I. Eur. J. Org. Chem. 2012; 5660
  • 47 Danilkina NA, Lyapunova AG, Khlebnikov AF, Starova GL, Bräse S, Balova IA. J. Org. Chem. 2015; 80: 5546
    CrossrefPubMedSuche in Google Scholar
  • 48 Geometry optimization of reactants and transition states were performed using B3LYP with the 6-31G++(d,p) basis set. Because of the open shell nature of the transition states, calculations on these structures were performed using BS-UB3LYP (broken-spin symmetry, unrestricted) calculations. For further computational details see the Supporting Information.
  • 49 Danilkina NA, Kulyashova AE, Khlebnikov AF, Bräse S, Balova IA. J. Org. Chem. 2014; 79: 9018
    CrossrefPubMedSuche in Google Scholar
  • 50 Danilkina NA, Bräse S, Balova IA. Synlett 2011; 517
    Thieme Connect
  • 51 Danilkina NA, Gurskaya LY, Vasilyev AV, Balova IA. Eur. J. Org. Chem. 2016; 739
  • 52 Lyapunova AG, D’yachenko AS, Danilkina NA. Russ. J. Org. Chem. 2017; 53: 800
    CrossrefSuche in Google Scholar
  • 53 Arnanz A, Moreno C, Marcos M.-L, González-Velasco J, Delgado S. Eur. J. Inorg. Chem. 2007; 5215
  • 54 Arnanz A, Marcos ML, Delgado S, González-Velasco J, Moreno C. J. Organomet. Chem. 2008; 693: 3457
    CrossrefSuche in Google Scholar
  • 55 η2-Co2(CO)6-Complex 11To an argon-flushed stirred solution of Co complex 10 (280 mg, 0.395 mmol) in absolute DCM (395 mL, c = 0.001 M) at room temperature was added BF3·OEt2 (84.0 mg, 73.0 μL, 0.593 mmol, 1.5 equiv). The resulting mixture was stirred at this temperature for 1 h and quenched with a saturated aqueous solution of NaHCO3. The organic layer was separated, washed with water, dried with anhydrous Na2SO4, and concentrated under reduced pressure to yield a crude product, which was purified by column chromatography using hexane/ethyl acetate (7:1) as the eluent to give 11 (193 mg, 72%) as a burgundy solid. The complex decomposed without melting upon heating to 300 °C. 1H NMR (400 MHz, CDCl3 ): δ = 7.93 (d, J = 8.3 Hz, 1 H), 7.87 (d, J = 8.1 Hz, 2 H), 7.75 (d, J = 8.3 Hz, 1 H), 7.50 (d, J = 8.1 Hz, 2 H), 7.47–7.43 (m, 2 H), 4.97 (s, 2 H), 3.73 (t, J = 5.2 Hz, 2 H), 2.84 (t, J = 5.2 Hz, 2 H), 2.46 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 200.1, 151.5, 145.0, 139.8, 139.4, 136.2, 130.9 (two CH signals overlap), 128.6, 126.5, 123.6, 123.5, 116.8, 101.4, 99.0, 80.6, 79.4, 57.7, 56.4, 23.6, 21.4. HRMS (ESI): m/z calcd for C28H17Co2NNaO8S2 [M + Na]+: 699.8957; found: 699.8921.
  • 56 Jones GB, Wright JM, Rush TM, Plourde GW, Kelton TF, Mathews JE, Huber RS, Davidson JP. J. Org. Chem. 1997; 62: 9379
    CrossrefSuche in Google Scholar
  • 57 4-Tosyl-1,2,7,8-tetradehydro-3,4,5,6-tetrahydrobenzo[4,5]thieno[2,3-e]azecine (1; Conditions f)To a cooled to 0 °C stirred solution of Co2(CO)6 complex 11 (30.7 mg, 0.04546 mmol) in acetone (4.5 mL) in an Ar atmosphere tetrabutylammonium fluoride hydrate ( 143 mg, 0.543 mmol calculated for TBAF·monohydrate) was added in three portions with an interval of 20 min. After completion of the reaction (TLC control, 90 min) the reaction mixture was poured into water, extracted with ethyl acetate, washed with water, dried over anhydrous Na2SO4, and the solvent was evaporated under reduced pressure. The crude product loaded on silica gel was purified by column chromatography using hexane/acetone (3:1) as the eluent to give enediyne 1 (8.0 mg, 45%) as a beige solid. The mp cannot be measured, because the Bergman cyclization occurs prior to melting. 1H NMR (400 MHz, CDCl3): δ = 7.97 (d, J = 6.9 Hz, 1 H), 7.83 (d, J = 7.9 Hz, 2 H), 7.78 (d, J = 6.9 Hz, 1 H), 7.52–7.46 (m, 2 H), 7.44 (d, J = 7.9 Hz, 2 H), 4.38 (s, 2 H), 3.64 (t, J = 4.4 Hz, 2 H), 2.97 (t, J = 4.4 Hz, 2 H), 2.41 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 144.8, 138.9, 136.5, 136.4, 130.8, 130.3, 129.0, 128.3, 127.2, 126.4, 124.0, 123.4, 105.0, 102.3, 82.5, 79.3, 52.2, 43.3, 23.4, 21.4. HRMS (ESI): m/z calcd for C22H17NNaO2S2 [M + Na]+: 414.0598; found: 414.0583.
  • 58 ASTM E698-01, Standard Test Method for Arrhenius Kinetic Constants for Thermally Unstable Materials. ASTM International: West Conshohocken, PA: 2001 www.astm.org
    CrossrefSuche in Google Scholar
  • 59 For the copies of thermograms, T onset and T peak values, Arrhenius plots and Ea calculation, see the Supporting Information.
  • 60 Prall M, Wittkopp A, Fokin AA, Schreiner PR. J. Comput. Chem. 2001; 22: 1605
    CrossrefSuche in Google Scholar
  • 61 Mohamed RK, Peterson PW, Alabugin IV. Chem. Rev. 2013; 113: 7089
    CrossrefPubMedSuche in Google Scholar
  • 62 Gold B, Dudley GB, Alabugin IV. J. Am. Chem. Soc. 2013; 135: 1558
    CrossrefPubMedSuche in Google Scholar
  • 63 Harris T, dos Passos Gomes G, Ayad S, Clark RJ, Lobodin VV, Tuscan M, Hanson K, Alabugin IV. Chem. 2017; 3: 629
    CrossrefSuche in Google Scholar
  • 64 Basak A, Bdour HM. D, Shain JC, Mandal S, Rudra KR, Nag S. Bioorg. Med. Chem. Lett. 2000; 10: 1321
    CrossrefPubMedSuche in Google Scholar
  • 65 Haberhauer G, Gleiter R, Fabig S. Org. Lett. 2015; 17: 1425
    CrossrefPubMedSuche in Google Scholar
  • 66 Zeidan TA, Kovalenko SV, Manoharan M, Alabugin IV. J. Org. Chem. 2006; 71: 962
    CrossrefPubMedSuche in Google Scholar
  • 67 For the details of HRMS studies, see the Supporting Information.
  • 68 Povirk LF, Wübker W, Köhnlein W, Hutchinson F. Nucleic Acids Res. 1977; 4: 3573
    CrossrefPubMedSuche in Google Scholar