Synthesis 2019; 51(03): 713-729
DOI: 10.1055/s-0037-1611059
paper
© Georg Thieme Verlag Stuttgart · New York

Concise Synthesis of Tryptanthrin Spiro Analogues with In Vitro Antitumor Activity Based on One-Pot, Three-Component 1,3-Dipolar Cycloaddition of Azomethine Ylides to Сyclopropenes

Alexander S. Filatov
a  Saint-Petersburg State University, Universitetskaya nab. 7/9, St. Petersburg 199034, Russian Federation   Email: alstepakov@yandex.ru
,
Nickolay A. Knyazev
b  Saint-Petersburg Academic University – Nanotechnology Research and Education Centre RAS, ul. Khlopina 8/3, St. Petersburg 194021, Russian Federation   Email: bovitali@yandex.ru
c  Institute of Cytology of the Russian Academy of Science, Tikhoretsky pr. 4, St. Petersburg 194064, Russian Federation
,
Stanislav V. Shmakov
b  Saint-Petersburg Academic University – Nanotechnology Research and Education Centre RAS, ul. Khlopina 8/3, St. Petersburg 194021, Russian Federation   Email: bovitali@yandex.ru
,
Alexey A. Bogdanov
d  ITMO University, Kronverksky pr. 49, St. Petersburg 197101, Russian Federation
e  St. Petersburg Clinical Scientific-Practical Center of Specialized Types of Medical Care (Oncology), Leningradskaya str., 68A, Pesochny village, St. Petersburg 197758, Russian Federation
,
Mikhail N. Ryazantsev
a  Saint-Petersburg State University, Universitetskaya nab. 7/9, St. Petersburg 199034, Russian Federation   Email: alstepakov@yandex.ru
,
Andrey A. Shtyrov
b  Saint-Petersburg Academic University – Nanotechnology Research and Education Centre RAS, ul. Khlopina 8/3, St. Petersburg 194021, Russian Federation   Email: bovitali@yandex.ru
,
Galina L. Starova
a  Saint-Petersburg State University, Universitetskaya nab. 7/9, St. Petersburg 199034, Russian Federation   Email: alstepakov@yandex.ru
,
Alexander P. Molchanov
a  Saint-Petersburg State University, Universitetskaya nab. 7/9, St. Petersburg 199034, Russian Federation   Email: alstepakov@yandex.ru
,
Anna G. Larina
a  Saint-Petersburg State University, Universitetskaya nab. 7/9, St. Petersburg 199034, Russian Federation   Email: alstepakov@yandex.ru
,
Vitali M. Boitsov*
b  Saint-Petersburg Academic University – Nanotechnology Research and Education Centre RAS, ul. Khlopina 8/3, St. Petersburg 194021, Russian Federation   Email: bovitali@yandex.ru
f  Institute of macromolecular compounds, Bolshoy pr. 31, St. Petersburg 199004, Russian Federation
g  Saint-Petersburg Scientific Center of the Russian Academy of Sciences, Universitetskaya Nab. 5, St. Petersburg 199034, Russian Federation
,
Alexander V. Stepakov*
a  Saint-Petersburg State University, Universitetskaya nab. 7/9, St. Petersburg 199034, Russian Federation   Email: alstepakov@yandex.ru
h  Saint-Petersburg State Institute of Technology, Moskovskii pr. 26, St. Petersburg 190013, Russian Federation
› Author Affiliations
We gratefully acknowledge the financial support from the Russian Foundation for Basic Research (Projects No. 18-33-00464 and 18-015-00443), the Program of Fundamental Research ‘Nanostructures: Physics, Chemistry, Biology, and Fundamentals of Technology’ of the Presidium of the Russian Academy of Sciences and SPbAU RAS state order (project 16.9790.2017/BCh). Skolkovo Foundation (grant agreement for Russian educational and scientific organisation no.7 dd. 19.12.2017) and Skolkovo Institute of Science and Technology (general agreement no. 3663-MRA dd. 25.12.2017).
Further Information

Publication History

Received: 19 July 2018

Accepted after revision: 12 September 2018

Publication Date:
10 October 2018 (online)


Dedicated to the memory of Prof. Rafael Kostikov. Teacher and friend.

Abstract

A simple, efficient and atom-economic method has been developed for the synthesis of complex alkaloid-like compounds with spiro-fused indolo[2,1-b]quinazoline and cyclopropa[a]pyrrolizine or 3-azabicyclo[3.1.0]hexane moieties. We have found that one-pot, three-component 1,3-dipolar cycloaddition reactions allow the desired products to be obtained from various cyclopropene derivatives with tryptanthrin-derived azomethine ylides generated in situ, in good to high yields and excellent diastereoselectivity. The possibility of ylide generation was exemplified by using α-amino acids (l-proline, l-4-thiazolidincarboxylic acid) and simplest peptides (dipeptide Gly-Gly, tripeptide Gly-Gly-Gly). Quantum chemical investigations indicate that the reaction proceeds through the S-shaped azomethine ylide, the interaction of which with cyclopropenes proceeds via a less sterically hindered endo-transition state. The antitumor activity of some of spiro-tryptanthrin derivatives against erythroleukemia (K562), cervical carcinoma (HeLa) and colon carcinoma (CT26) cell lines was evaluated in vitro by MTS-assay.

Supporting Information

 
  • References

    • 1a Schindler F. Zahner H. Arch. Microbiol. 1971; 79: 187
    • 1b Danz H. Stoyanova S. Wippich P. Brattstroem A. Hamburger M. Planta Med. 2001; 67: 411
    • 1c Murakami T. Kishi A. Sakurama T. Matsuda H. Yoshikawa M. Heterocycles 2001; 54: 957
    • 1d Sharma VM. Prasanna P. Seshu KV. A. Renuka B. Rao CV. L. Kumar GS. Narasimhulu CP. Babu PA. Puranik RC. Subramanyam D. Venkateswarlu A. Rajagopal S. Kumar KB. S. Rao CS. Mamidi NV. S. Deevi DS. Ajaykumar R. Rajagopalan R. Bioorg. Med. Chem. Lett. 2002; 12: 2303
    • 1e Bergman J. Lindstroem J. Tilstam U. Tetrahedron 1985; 41: 2879
    • 1f Honda G. Tosirisuk V. Tabata M. Planta Med. 1980; 38: 275
    • 1g Wu XY. Liu YH. Sheng WY. Sun J. Qin GW. Planta Med. 1997; 63: 55
    • 1h Yoshikawa M. Murakami T. Kishi A. Sakurama T. Matsuda H. Nomura M. Matsuda H. Kubo M. Chem. Pharm. Bull. 1998; 46: 886
    • 2a Chan HL. Yip HY. Mak NK. Leung KN. Cell. Mol. Immunol. 2009; 6: 335
    • 2b Yu ST. Chern JW. Chen TM. Chiu YF. Chen HT. Chen YH. Acta Pharmacol. Sin. 2010; 31: 259
    • 2c Miao S. Shi X. Zhang H. Wang S. Sun J. Hua W. Miao Q. Zhao Y. Zhang C. Int. J. Mol. Sci. 2011; 12: 3831
    • 2d Motoki T. Takami Y. Yagi Y. Tai A. Yamamoto I. Gohda E. Biol. Pharm. Bull. 2005; 28: 260
    • 3a Iwaki K. Ohashi E. Arai N. Kohno K. Ushio S. Taniguchi M. Fukuda S. J. Ethnopharmacol. 2011; 134: 450
    • 3b Takei Y. Kunikata T. Aga M. Inoue S. Ushio S. Iwaki K. Ikeda M. Kurimoto M. Biol. Pharm. Bull. 2003; 26: 365
    • 3c Ishihara T. Kohno K. Ushio S. Iwaki K. Ikeda M. Kurimoto M. Eur. J. Pharmacol. 2000; 407: 197
  • 4 Recio MC. Cerda-Nicolas M. Potterat O. Hamburger M. Rios JL. Planta Med. 2006; 72: 539
    • 5a Bandekar PP. Roopnarine KA. Parekh VJ. Mitchell TR. Novak MJ. Sinden RR. J. Med. Chem. 2010; 53: 3558
    • 5b Krivogorsky B. Grundt P. Yolken R. Jones-Brando L. Antimicrob. Agents Chemother. 2008; 52: 4466
    • 5c Scovill J. Blank E. Konnick M. Nenortas E. Shapiro T. Antimicrob. Agents Chemother. 2002; 46: 882
  • 6 Bhattacharjee AK. Skanchy DJ. Jennings B. Hudson TH. Brendle JJ. Werbovetz KA. Bioorg. Med. Chem. 2002; 10: 1979
  • 7 Honda G. Tabata M. Planta Med. 1979; 36: 85
  • 8 Bhattacharjee AK. Hartell MG. Nichols DA. Hicks RP. Stanton B. van Hamont JE. Milhous WK. Eur. J. Med. Chem. 2004; 39: 59
  • 9 Jao C.-W. Lin W.-C. Wu Y.-T. Wu P.-L. J. Nat. Prod. 2008; 71: 1275
  • 10 Yang S. Li X. Hu F. Li Y. Yang Y. Yan J. Kuang C. Yang Q. J. Med. Chem. 2013; 56: 8321
    • 11a Hwang J.-M. Oh T. Kaneko T. Upton AM. Franzblau SG. Ma Z. Cho S.-N. Kim P. J. Nat. Prod. 2013; 76: 354
    • 11b Mitscher LA. Baker W. Med. Res. Rev. 1998; 18: 363
  • 12 Seya K. Yamaya A. Kamachi S. Murakami M. Kitahara H. Kawakami J. Okumura K. Murakami M. Motomura S. Furukawa K.-I. J. Nat. Prod. 2014; 77: 1413
  • 13 Liao X. Leung KN. Chem.-Biol. Interact. 2013; 203: 512
  • 14 Guentner A. Seybold G. Wagenblast G. Ger. Offen DE4114990 A1, 1992
  • 15 Kawaguchi H. Mizuta Y. Sugai F. Saito S. Matsumoto S. Fukami T. Yamazato I. Uegaito H. Tanaka Y. Akiba N. Watanabe Y. Iwasaki H. Hanatani Y. Eur. Pat. Appl EP0718298A1, 1996
  • 16 Kawakami J. Kikuchi K. Chiba K. Matsushima N. Yamaya A. Ito S. Nagaki M. Kitahara H. Anal. Sci. 2009; 25: 1385
  • 17 Gruznev DV. Chubenko DN. Zotov AV. Saranin AA. J. Phys. Chem. C 2010; 114: 14489
    • 18a Tucker AM. Grundt P. ARKIVOC 2012; (i): 546
    • 18b Mei G.-J. Bian C.-Y. Li G.-H. Xu S.-L. Zheng W.-Q. Shi F. Org. Lett. 2017; 19: 3219
    • 18c Wang C. Zhang L. Ren A. Lu P. Wang Y. Org. Lett. 2013; 15: 2982
    • 18d Kingi N. Bergman J. J. Org. Chem. 2016; 81: 7711
    • 18e Kang G. Luo Z. Liu C. Gao H. Wu Q. Wu H. Jiang J. Org. Lett. 2013; 15: 4738
    • 18f Bowman WR. Elsegood MR. J. Steina T. Weaver GW. Org. Biomol. Chem. 2007; 5: 103
    • 18g Jia F.-C. Zhou Z.-W. Xu C. Wu Y.-D. Wu A.-X. Org. Lett. 2016; 16: 2942
    • 18h Liao F.-M. Liu Y.-L. Yu J.-S. Zhoua F. Zhou J. Org. Biomol. Chem. 2015; 13: 8906
    • 18i Li X. Huang H. Yu C. Zhang Y. Li H. Wang W. Org. Lett. 2016; 18: 5744
    • 18j Moskovkina TV. Kalinovskii AI. Makhan’kov VV. Russ. J. Org. Chem. 2012; 48: 123
    • 18k Moskovkina TV. Denisenko MV. Kalinovskii AI. Stonik VA. Russ. J. Org. Chem. 2013; 49: 1740
    • 18l Chen W.-L. Liu C.-X. Xiao H.-P. Jiang J. Synlett 2016; 27: 1989
    • 18m Mason JJ. Janosik T. Bergman J. Synthesis 2009; 3642
    • 18n Batanero B. Barba F. Tetrahedron Lett. 2006; 47: 8201
    • 18o Nelson AC. Kalinowski ES. Jacobson TL. Grundt P. Tetrahedron Lett. 2013; 54: 6804
    • 18p Abe T. Itoh T. Choshi T. Hibino S. Ishikura M. Tetrahedron Lett. 2014; 55: 5268
    • 19a Lown JW. In 1,3-Dipolar Cycloaddition Chemistry . Vol. 1. Padwa A. Wiley; New York: 1984: 2
    • 19b Gothelf KV. In Cycloaddition Reactions in Organic Synthesis . Kobayashi S. Jørgensen KA. Wiley-VCH; Weinheim: 2002: 211
    • 19c Coldham I. Hufton R. Chem. Rev. 2005; 105: 2765
    • 19d Pandey G. Banerjee P. Gadre SR. Chem. Rev. 2006; 106: 4484
    • 19e Zhao H.-W. Yang Z. Meng W. Tian T. Li B. Song X.-Q. Chen X.-Q. Pang H.-L. Adv. Synth. Catal. 2015; 357: 2492
    • 19f Shi F. Tao Z.-L. Luo S.-W. Tu S.-J. Gong L.-Z. Chem. Eur. J. 2012; 18: 6885
    • 19g Wang C.-S. Zhu R.-Y. Zheng J. Shi F. Tu S.-J. J. Org. Chem. 2015; 80: 512
    • 19h Dai W. Jiang X.-L. Wu Q. Shi F. Tu S.-J. J. Org. Chem. 2015; 80: 5737
    • 19i Shi F. Zhu R.-Y. Liang X. Tu S.-J. Adv. Synth. Catal. 2013; 355: 2447
    • 19j Gothelf AS. Gothelf KV. Hazell RG. Jørgensen KA. Angew. Chem. Int. Ed. 2002; 41: 4236
    • 19k Liu T.-L. He Z.-L. Li Q.-H. Tao H.-Y. Wang C.-J. Adv. Synth. Catal. 2015; 357: 1713
    • 19l Nájera C. Sansano JM. Curr. Org. Chem. 2003; 7: 1105
    • 19m Döndas HA. de Gracia Retamosa M. Sansano JM. Synthesis 2017; 49: 2819
    • 19n Nair V. Sheela KC. Rath NP. Chem. Lett. 2000; 29: 980
    • 19o Wang Y.-M. Zhang H.-H. Li C. Fanand T. Shi F. Chem. Commun. 2016; 1804
    • 19p Shirsat PK. Khomane NB. Mali PR. Maddi RR. Nanubolu JB. Meshram HM. ChemistrySelect 2017; 2: 11218
    • 19q Buev EM. Moshkin VS. Sosnovskikh VY. J. Org. Chem. 2017; 82: 12827
    • 19r Buev EM. Moshkin VS. Sosnovskikh VY. Org. Lett. 2016; 18: 1764
    • 19s Xia P.-J. Li J. Qian Y.-L. Zhao Q.-L. Xiang H.-Y. Xiao J.-A. Chen X.-Q. Yang H. J. Org. Chem. 2018; 83: 2948
    • 20a Shahrestani N. Salahi F. Tavakoli N. Jadidi K. Hamzehloueian M. Notash B. Tetrahedron: Asymmetry 2015; 26: 1117
    • 20b Akondi AM. Mekala S. Kantam ML. Trivedi R. Chowhan LR. Das A. New J. Chem. 2017; 41: 873
    • 20c Lakshmi NV. Thirumurugan P. Jayakumar C. Perumal PT. Synlett 2010; 955
    • 20d Babu AR. S. Raghunathan R. Tetrahedron Lett. 2006; 47: 9221
    • 20e Azizian J. Karimi AR. Mohammadi AA. Mohammadizadeh MR. Synthesis 2004; 2263
    • 20f Haddad S. Boudriga S. Porzio F. Soldera A. Askri M. Knorr M. Rousselin Y. Kubicki MM. Golzand C. Strohmann C. J. Org. Chem. 2015; 80: 9064
    • 20g Hamzehloueian M. Sarrafi Y. Aghaei Z. RSC Adv. 2015; 5: 76368
    • 20h Malathi K. Kanchithalaivan S. Ranjith Kumar R. Almansour AI. Suresh Kumar R. Arumugam N. Tetrahedron Lett. 2015; 56: 6132
    • 20i Gavaskar D. Suresh Babu AR. Raghunathan R. Dharani M. Balasubramanian S. J. Organomet. Chem. 2014; 768: 128
    • 20j Moemeni M. Arvinnezhad H. Samadi S. Salahi F. Jadidi K. Notash B. J. Heterocycl. Chem. 2015; 52: 944
    • 20k Rao JN. S. Raghunathan R. Tetrahedron Lett. 2015; 56: 1539
    • 20l Barkov AY. Zimnitskiy NS. Kutyashev IB. Korotaev VY. Sosnovskikh VY. Chem. Heterocycl. Compd. 2017; 53: 1315
    • 20m Barkov AY. Zimnitskiy NS. Korotaev VY. Kutyashev IB. Moshkin VS. Sosnovskikh VY. Chem. Heterocycl. Compd. 2017; 53: 451
  • 21 Filatov AS. Knyazev NA. Molchanov AP. Panikorovsky TL. Kostikov RR. Larina AG. Boitsov VM. Stepakov AV. J. Org. Chem. 2017; 82: 959
  • 22 Filatov AS. Knyazev NA. Ryazantsev MN. Suslonov VV. Larina AG. Molchanov AP. Kostikov RR. Boitsov VM. Stepakov AV. Org. Chem. Front. 2018; 5: 595

    • For reviews of the chemistry of cyclopropene compounds, see:
    • 23a Baird MS. In Methods of Organic Chemistry (Houben Weyl) . Vol. E17d. de Meijere A. Thieme; Stuttgart: 1997: 2781
    • 23b Carter FL. Frampton VL. Chem. Rev. 1964; 64: 497
    • 23c Padwa A. Acc. Chem. Res. 1979; 12: 310
    • 23d Komatsu K. Kitagawa T. Chem. Rev. 2003; 103: 1371
    • 23e Rubin M. Rubina M. Gevorgyan V. Synthesis 2006; 1221
    • 23f Rubin M. Rubina M. Gevorgyan V. Chem. Rev. 2007; 107: 3117
    • 23g Zhu Z.-B. Wei Y. Shi M. Chem. Soc. Rev. 2011; 40: 5534
    • 23h Miege F. Meyer C. Cossy J. Beilstein J. Org. Chem. 2011; 7: 717
    • 23i Song C. Wang J. Xu Z. Acta Chim. Sin. (Chin. Ed.) 2015; 73: 1114
    • 24a Otero-Fraga J. Montesinos-Magraner M. Mendoza A. Synthesis 2016; 49: 802
    • 24b Pascual-Escudero A. de Cózar A. Cossío FP. Adrio J. Carretero JC. Angew. Chem. Int. Ed. 2016; 55: 15334
    • 24c Otero-Fraga J. Suárez-Pantiga S. Montesinos-Magraner M. Rhein D. Mendoza A. Angew. Chem. Int. Ed. 2017; 56: 12962
    • 25a Diev VV. Kostikov RR. Gleiter R. Molchanov AP. J. Org. Chem. 2006; 71: 4066
    • 25b Diev VV. Stetsenko ON. Tung TQ. Kopf J. Kostikov RR. Molchanov AP. J. Org. Chem. 2008; 73: 2396
  • 26 Mancebo-Aracil J. Muñoz-Guillena MJ. Such-Basáñez I. Sansano-Gil JM. ChemPlusChem 2012; 77: 770
  • 27 CCDC 1567190 (4aaa) and CCDC 1821071 (4aaa′) contain the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures
  • 28 For the synthesis of tryptanthrins, see: Yang S. Li X. Hu F. Li Y. Yang Y. Yan J. Kuang C. Yang Q. J. Med. Chem. 2013; 56: 8321

    • For the synthesis of cyclopropenes, see:
    • 29a Breslow R. Chang HW. J. Am. Chem. Soc. 1961; 83: 2367
    • 29b D’yakonov IA. Komendantov MI. Gokhmanova I. Kostikov RR. Zh. Obshch. Khim. 1959; 29: 3848
    • 29c Farnum DG. Burr M. J. Am. Chem. Soc. 1960; 82: 2651
    • 29d White EH. Winter RE. K. Graeve R. Zirngibl U. Friend EW. Maskill H. Mende U. Kreiling G. Reisenauer HP. Maier G. Chem. Ber. 1981; 114: 3906
    • 29e Li H. Rao PN. P. Habeeb AG. Knaus EE. Drug Dev. Res. 2002; 57: 6
  • 30 Frisch MJ. Trucks GW. Schlegel HB. Scuseria GE. Robb MA. Cheeseman JR. Scalmani G. Barone V. Mennucci B. Petersson GA. Nakatsuji H. Caricato M. Li X. Hratchian HP. Izmaylov AF. Bloino J. Zheng G. Sonnenberg JL. Hada M. Ehara M. Toyota K. Fukuda R. Hasegawa J. Ishida M. Nakajima T. Honda Y. Kitao O. Nakai H. Vreven T. Montgomery JrJ. A. Peralta JE. Ogliaro F. Bearpark MJ. Heyd J. Brothers EN. Kudin KN. Staroverov VN. Kobayashi R. Normand J. Raghavachari K. Rendell AP. Burant JC. Iyengar SS. Tomasi J. Cossi M. Rega N. Millam NJ. Klene M. Knox JE. Cross JB. Bakken V. Adamo C. Jaramillo J. Gomperts R. Stratmann RE. Yazyev O. Austin AJ. Cammi R. Pomelli C. Ochterski JW. Martin RL. Morokuma K. Zakrzewski VG. Voth GA. Salvador P. Dannenberg JJ. Dapprich S. Daniels AD. Farkas O. Foresman JB. Ortiz JV. Cioslowski J. Fox DJ. Gaussian 09, Revision A.01 Gaussian, Inc; Wallingford: 2009