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

Natalia A. Danilkina; Andrey M. Rumyantsev; Anna L. Lyapunova; Alexander S. D’yachenko; Alexander F. Khlebnikov; Irina A. Balova

doi:10.1055/s-0037-1610352

Synlett, Table of Contents

Synlett 2019; 30(02): 161-166
DOI: 10.1055/s-0037-1610352

letter

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

Natalia A. Danilkina

^aInstitute of Chemistry, Saint Petersburg State University (SPbSU), Universitetskaya nab. 7/9, 199034 Saint Petersburg, Russia Email: i.balova@spbu.ru

,

Andrey M. Rumyantsev

^bDepartment of Genetics and Biotechnology, Saint Petersburg State University (SPbSU), Universitetskaya nab. 7/9, 199034 Saint Petersburg, Russia

,

Anna L. Lyapunova

^aInstitute of Chemistry, Saint Petersburg State University (SPbSU), Universitetskaya nab. 7/9, 199034 Saint Petersburg, Russia Email: i.balova@spbu.ru

,

Alexander S. D’yachenko

^aInstitute of Chemistry, Saint Petersburg State University (SPbSU), Universitetskaya nab. 7/9, 199034 Saint Petersburg, Russia Email: i.balova@spbu.ru

,

Alexander F. Khlebnikov

^aInstitute of Chemistry, Saint Petersburg State University (SPbSU), Universitetskaya nab. 7/9, 199034 Saint Petersburg, Russia Email: i.balova@spbu.ru

,

Irina A. Balova *

^aInstitute of Chemistry, Saint Petersburg State University (SPbSU), Universitetskaya nab. 7/9, 199034 Saint Petersburg, Russia Email: i.balova@spbu.ru

› Author Affiliations

Abstract

All articles of this category

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

Full Text

References

References and Notes
1 Nicholas KM, Pettit R. J. Organomet. Chem. 1972; 44: C21
2 Connor RE, Nicholas KM. J. Organomet. Chem. 1977; 125: C45
3 Green JR. Curr. Org. Chem. 2001; 5: 809
4 Teobald BJ. Tetrahedron 2002; 58: 4133
5 Nicholas KM. J. Org. Chem. 2015; 80: 6943
6 Bavetsias V, Henderson EA, McDonald E. Tetrahedron 2007; 63: 1537
7 Henderson EA, Bavetsias V, Theti DS, Wilson SC, Clauss R, Jackman AL. Bioorg. Med. Chem. 2006; 14: 5020
8 Amin J, Motevalli M, Richards CJ. J. Organomet. Chem. 2015; 776: 43
9 Wells SM, Widen JC, Harki DA, Brummond KM. Org. Lett. 2016; 18: 4566
10 Closser KD, Quintal MM, Shea KM. J. Org. Chem. 2009; 74: 3680
11 Kaneda K, Naruse R, Yamamoto S. Org. Lett. 2017; 19: 1096
12 Kaneda K, Fujita M, Naruse R. Heterocycles 2016; 92: 291
13 Asamizu T, Naruse R, Yongxue G, Kaneda K. Tetrahedron Lett. 2015; 56: 4674
14 Christie SD. R, Davoile RJ, Jones RC. F. Org. Biomol. Chem. 2006; 4: 2683
15 Akimura N, Fujii A, Kamada F, Nogiwa R, Yamamoto S, Sato T, Ishikawa S, Okazaki T, Kaneda K. Synthesis 2016; 48: 3931
16 Hernández JN, Ramírez MA, Rodríguez ML, Martín VS. Org. Lett. 2008; 10: 2349
17 Grammatoglou K, Bolsakova J, Jirgensons A. RSC Adv. 2017; 7: 27530
18 Igawa K, Aoyama S, Kawasaki Y, Kashiwagi T, Seto Y, Ni R, Mitsuda N, Tomooka K. Synlett 2017; 28: 2110
19 Carrillo R, Martín T, López-Rodríguez M, Crisóstomo FP. Org. Lett. 2014; 16: 552
20 Ni R, Mitsuda N, Kashiwagi T, Igawa K, Tomooka K. Angew. Chem. Int. Ed. 2015; 54: 1190
21 Hagendorn T, Braese S. RSC Adv. 2014; 4: 15493
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
23 Kar M, Basak A. Chem. Rev. 2007; 107: 2861
24 Basak A, Roy S, Roy B, Basak A. Curr. Top. Med. Chem. 2008; 8: 487
25 Klein M, Walenzyk T, König B. Collect. Czech. Chem. Commun. 2004; 69: 945
26 Basak A, Mandal S, Bag SS. Chem. Rev. 2003; 103: 4077
27 Bhattacharya P, Basak A, Campbell A, Alabugin IV. Mol. Pharmaceutics 2018; 15: 768
28 Shain JC, Khamrai UK, Basak A. Tetrahedron Lett. 1997; 38: 6067
29 Basak A, Mandal S, Das AK, Bertolasi V. Bioorg. Med. Chem. Lett. 2002; 12: 873
30 Hatial I, Jana S, Bisai S, Das M, Ghosh AK, Anoop A, Basak A. RSC Adv. 2014; 4: 28041
31 Basak A, Kar M. Bioorg. Med. Chem. 2008; 16: 4532
32 Du Y, Creighton CJ, Yan Z, Gauthier DA, Dahl JP, Zhao B, Belkowski SM, Reitz AB. Bioorg. Med. Chem. 2005; 13: 5936
33 Poloukhtine A, Popik VV. J. Am. Chem. Soc. 2007; 129: 12062
34 Dutta S, Basak A, Dasgupta S. Bioorg. Med. Chem. 2009; 17: 3900
35 Hatial I, Addy PS, Ghosh AK, Basak A. Tetrahedron Lett. 2013; 54: 854
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
37 Magnus P. Tetrahedron 1994; 50: 1397
38 Roy S, Anoop A, Biradha K, Basak A. Angew. Chem. Int. Ed. 2011; 50: 8316
39 Roy B, Basak A. Synlett 2006; 2804
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
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
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
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
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
50 Danilkina NA, Bräse S, Balova IA. Synlett 2011; 517
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
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
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
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
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
61 Mohamed RK, Peterson PW, Alabugin IV. Chem. Rev. 2013; 113: 7089
62 Gold B, Dudley GB, Alabugin IV. J. Am. Chem. Soc. 2013; 135: 1558
63 Harris T, dos Passos Gomes G, Ayad S, Clark RJ, Lobodin VV, Tuscan M, Hanson K, Alabugin IV. Chem. 2017; 3: 629
64 Basak A, Bdour HM. D, Shain JC, Mandal S, Rudra KR, Nag S. Bioorg. Med. Chem. Lett. 2000; 10: 1321
65 Haberhauer G, Gleiter R, Fabig S. Org. Lett. 2015; 17: 1425
66 Zeidan TA, Kovalenko SV, Manoharan M, Alabugin IV. J. Org. Chem. 2006; 71: 962
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

Supplementary Material

Supporting Information