Synthesis 2016; 48(22): 3907-3916
DOI: 10.1055/s-0035-1562497
paper
© Georg Thieme Verlag Stuttgart · New York

Multicomponent Approach to Bioactive Peptide–Ecdysteroid Conjugates: Creating Diversity at C6 by Means of the Ugi Reaction

Giordano Lesma
a   Dipartimento di Chimica, Università di Milano, via Golgi 19, Milano, 20133, Italy
,
Andrea Luraghi
a   Dipartimento di Chimica, Università di Milano, via Golgi 19, Milano, 20133, Italy
,
Giulia Rainoldi
a   Dipartimento di Chimica, Università di Milano, via Golgi 19, Milano, 20133, Italy
,
Elena Mattiuzzo
b   Dipartimento di salute della Donna e del Bambino, Università di Padova, Via Giustiniani 3, Padova, 35128, Italy   eMail: alessandra.silvani@unimi.it
,
Roberta Bortolozzi
b   Dipartimento di salute della Donna e del Bambino, Università di Padova, Via Giustiniani 3, Padova, 35128, Italy   eMail: alessandra.silvani@unimi.it
,
Giampietro Viola
b   Dipartimento di salute della Donna e del Bambino, Università di Padova, Via Giustiniani 3, Padova, 35128, Italy   eMail: alessandra.silvani@unimi.it
,
Alessandra Silvani*
a   Dipartimento di Chimica, Università di Milano, via Golgi 19, Milano, 20133, Italy
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received: 16. März 2016

Accepted after revision: 17. Mai 2016

Publikationsdatum:
01. Juli 2016 (online)


Abstract

An efficient multicomponent protocol has been developed to access two different kinds of peptide–ecdysteroid conjugates. The approach exploits the reactivity of the 6-keto-7-ene group of 20-OH-ecdysone, allowing the unprecedented preparation of 6-amino and 6-isocyanide derivatives. The ecdysteroid derivatives were further employed in the Ugi reaction, together with formaldehyde and various structurally diverse carboxylic acids, isocyanides and amines, to afford a small family of potential multidrug-resistance modulators.

Supporting Information

 
  • References

    • 1a Dinan L, Harmatha J, Volodin V, Lafont R In Ecdysone: Structures and Functions . Smagghe G. Springer; Dordrecht, The Netherlands: 2009: 3
    • 1b Dinan L. Eur. J. Entomol. 1995; 92: 271
    • 2a No D, Yao TP, Evans RM. Proc. Natl. Acad. Sci. U.S.A. 1996; 93: 3346
    • 2b Saez E, Nelson MC, Eshelman B, Banayo E, Koder A, Cho GJ, Evans RM. Proc. Natl. Acad. Sci. U.S.A. 2000; 97: 14512
    • 3a Lafont R, Dinan L. J. Insect. Sci. 2003; 3: 1
    • 3b Dinan L. Phytochemistry 2001; 57: 325
  • 4 Oehme I, Bösser S, Zörnig M. Cell Death Differ. 2006; 13: 189
    • 5a Vágvölgyi M, Martins A, Csábi J, Dankó B, Molnár J, Tóth G, Hunyadi A. Planta Med. 2015; 81-SL5A_01
    • 5b Martins A, Sipos P, Dér K, Csábi J, Miklos W, Berger W, Zalatnai A, Amaral L, Molnár J, Szabó-Révész P, Hunyadi A. BioMed Res. Int. 2015; Article ID 895360
    • 5c Martins A, Csábi J, Balázs A, Kitka D, Amaral L, Molnár J, Simon A, Tóth G, Hunyadi A. Molecules 2013; 18: 15255
    • 5d Martins A, Tóth N, Ványolós A, Béni Z, Zupkó I, Molnár J, Báthori M, Hunyadi A. J. Med. Chem. 2012; 55: 5034
  • 6 Palmeira A, Sousa E, Vasconcelos MH, Pinto M. Curr. Med. Chem. 2012; 19: 1946
    • 7a Lesma G, Sacchetti A, Bai R, Basso G, Bortolozzi R, Hamel E, Silvani A, Vaiana N, Viola G. Mol. Diversity 2014; 18: 357
    • 7b Lesma G, Bassanini I, Bortolozzi R, Colletto C, Bai R, Hamel E, Meneghetti F, Rainoldi G, Stucchi M, Sacchetti A, Silvani A, Viola G. Org. Biomol. Chem. 2015; 13: 11633
    • 8a Rivera DG, Vasco AV, Echemendía R, Concepción O, Pérez CS, Gavín JA, Wessjohann LA. Chem. Eur. J. 2014; 20: 13150
    • 8b Pérez-Labrada K, Méndez Y, Brouard I, Rivera DG. ACS Comb. Sci. 2013; 15: 320
    • 8c Rivera DG, Wessjohann LA. Molecules 2007; 12: 1890
    • 9a Swaan PW, Hillgren KM, Szoka FC. Jr, Øie S. Bioconjugate Chem. 1997; 8: 520
    • 9b Lee S, Kim K, Kumar TS, Lee J, Kim SK, Lee DY, Lee YK, Byun Y. Bioconjugate Chem. 2005; 16: 615
  • 10 Banerjee A, Sergienko E, Vasile S, Gupta V, Vouri K, Wipf P. Org. Lett. 2009; 11: 65
    • 11a Stucchi M, Cairati S, Cetin-Atalay R, Christodoulou MS, Grazioso G, Pescitelli G, Silvani A, Yildirim DC, Lesma G. Org. Biomol. Chem. 2015; 13: 4993
    • 11b Lesma G, Meneghetti F, Sacchetti A, Stucchi M, Silvani A. Beilstein J. Org. Chem. 2014; 10: 1383
    • 11c Lesma G, Cecchi R, Crippa S, Giovanelli P, Meneghetti F, Musolino M, Sacchetti A, Silvani A. Org. Biomol. Chem. 2012; 10: 9004
  • 12 Eckert H. Molecules 2012; 17: 1074
    • 13a van Berkel SS, Bögels BG. M, Wijdeven MA, Westermann B, Rutjes FP. J. T. Eur. J. Org. Chem. 2012; 19: 3543
    • 13b Shaabani A, Maleki A, Hossein Rezayan A, Sarvary A. Mol. Diversity 2011; 15: 41
    • 13c Pando O, Stark S, Denkert A, Porzel A, Preusentanz R, Wessjohann LA. J. Am. Chem. Soc. 2011; 133: 7692
  • 14 Suksamrarn A, Pattanaprateep P. Tetrahedron 1995; 51: 10633
  • 15 Silvani A, Lesma G, Crippa S, Vece V. Tetrahedron 2014; 70: 3994
  • 16 Polisar JG, Norton JR. Tetrahedron 2012; 68: 10236
  • 17 Ganem B. Acc. Chem. Res. 2009; 42: 463
    • 18a Kovganko NV, Ananich SK, Sokolov SN, Chernov YG. Chem. Nat. Compd. 2012; 47: 944
    • 18b Shafikov RV, Urazaeva YR, Afon’kina SR, Savchenko RG, Khalilov LM, Odinokov VN. Russ. J. Org. Chem. 2009; 45: 1456
    • 18c Galyautdinov IV, Ves’kina NA, Afon’kina SR, Khalilov LM, Odinokov VN. Russ. J. Org. Chem. 2006; 42: 1333
  • 19 Hoffman C, Tanke RS, Miller MJ. J. Org. Chem. 1989; 54: 3750
  • 20 Zhu J, Wu X, Danishefsky SJ. Tetrahedron Lett. 2009; 50: 577
  • 21 Dupuis M, Flego M, Molinari A, Cianfriglia M. HIV Med. 2003; 4: 338
  • 22 Romagnoli R, Baraldi PG, Carrion MD, Cruz-Lopez O, Lopez Cara LC, Balzarini J, Hamel E, Canella A, Fabbri E, Gambari R, Basso G, Viola G. Bioorg. Med. Chem. Lett. 2009; 19: 2022
  • 23 Frey T, Yue S, Haugland RP. Cytometry 1995; 20: 228