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Does the Solid-Phase Synthesis of a Tetrapeptide Represent a Challenge at the Onset of the XXI Century? The Case of Cyclo [(3R)-3-hydroxydecanoyl-l-seryl-(3R)-3-hydroxydecanoyl-l-seryl]

  • Bruce Merrifield Commemorative Issue
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Abstract

At the beginning of the XXI century, 43 years after the description of the first solid-phase synthesis of a tetrapeptide by Bruce Merrifield, the synthesis of a tetrapeptide may still represent a synthetic challenge. This is the case of serratamolide, a cyclic tetradepsipeptide originally found in a culture of Serratia marcescens, which exhibits interesting properties as a chemotherapeutic agent. Here we explore several methodologies for the synthesis of serratamolide in order to find a strategy that allows its preparation for further biological studies.

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Fig. 1.
Scheme 1.
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Scheme 2.
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Scheme 3.
Scheme 4.
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Abbreviations

ACH:

α-cyano-4-hydroxy-cinnamic acid

AM:

p-(R,S)-α-{1-[(9-fluorenyl)methoxyformamido]-2,4-dimethoxybenzyl}phenoxyacetic acid

AcOEt:

ethyl acetate

AcOH:

acetic acid

BuLi:

n-butyl lithium

2-ClTrt:

2-chlorotrityl resin

Da:

Dalton

DCM:

dichloromethane

β-DEX:

β-dextrane

DIA:

diisopropylamine

DIEA:

diisopropylethylamine

DIPCDI:

N,N′-diisopropylcarbodiimide

DMAP:

4-dimethylaminopyridine

DMF:

N,N-dimethylformamide

EDC:

1-ethyl-3-(3-dimethylaminopropyl)carbodiimide

ESI-MS:

electrospray ionization-mass spectrometry

Fmoc:

9-fluorenylmethoxycarbonyl

Fmoc-l-Ser(tBu)-OH:

N-α-(9-fluorenylmethoxycarbonyl)-O-t-butyl-l-serine

GC–MS:

gas chromatography–mass spectrometry

β-HA:

β-hydroxydecanoic acid

HATU:

1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo-[4,5-b]pyridinium hexafluorophosphate 3-oxide

HMPA:

hexamethylphosphoramide

1H-NMR:

nuclear magnetic resonance of proton

HOAt:

7-aza-1-hydroxybenzotriazole

HOBt:

1-hydroxybenzotriazole

HPLC:

high-performance liquid chromatography

HPLC–MS:

high-performance liquid chromatography–mass spectrometry

M :

molecular weight

MALDI:

matrix-assisted laser desorption ionization

MALDI-TOF:

matrix-assisted laser desorption ionization-time-of-flight

MeCN:

acetonitrile

MeOH:

methanol

NMP:

N-methylpyrrolidone

NMR:

nuclear magnetic resonance

PyAOP:

(7-azabenzotriazol-1-yl-oxy)tripyrrolidinophosphonium hexafluorophosphate

PyBOP:

benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate

Rf:

retention factor

RP-HPLC:

reverse phase-high performance liquid chromatography

tBu:

tert-butyl

TFA:

trifluoroacetic acid

THF:

tetrahydrofurane

TIS:

triisopropylsilane

TLC:

thin layer chromatography

t r :

retention time

References

  • Albericio F., Cases M., Alsina J., Triolo S. A., Carpino L. A., Kates S. A. (1997) Tetrahedron Lett. 38:4853–4856

    Article  CAS  Google Scholar 

  • Atherton E., Sheppard R. (1989). Solid Phase Synthesis. A Practical Approach. IRL Press, Oxford

    Google Scholar 

  • Barlos K., Chatzi O., Gatos D., Stavaropoulos G. (1991) Int. J. Peptide Protein Res. 37:513–520

    CAS  Google Scholar 

  • Cartwright N. (1957) Biochem. J. 67:663–669

    PubMed  CAS  Google Scholar 

  • Escobar-Díaz, E., López-Martín, E. M., Hernández del Cerro, M., Puig-Kroger, A., Soto-Cerrato, V., Montaner, B., Giralt, E., García-Marco, J. A., Pérez-Tomás, R. and Garcia-Prado, A.: 2005, Leukemia, 1–8

  • Ganesan A. (2003) Methods Enzymol. 369 (Combinatorial Chemistry, part B):415–434

    Article  PubMed  CAS  Google Scholar 

  • Goodman M., Levine L. (1964) J. Am. Chem. Soc. 86:2918

    Article  CAS  Google Scholar 

  • Iwata, T., Iwamoto, O. and Sugiyama, H.: 1990, Patent EP 0357 428 A1

  • Kaiser E., Colescott R. L., Bossiger C. D., Cook P. I. (1970) Anal. Biochem. 34:595–598

    Article  PubMed  CAS  Google Scholar 

  • Kawai Y., Yano I., Kaneda K. (1998) Eur. J. Biochem. 171:73–80

    Article  Google Scholar 

  • Lloyd-Williams P., Albericio F., Giralt E. (1993) Tetrahedron 49:11065–11133

    Article  CAS  Google Scholar 

  • Matsuyama T., Murakami T., Fujita S., Yano I. (1986) J. Gen. Microbiol. 132:865–875

    CAS  Google Scholar 

  • McKenzie A., Widdows S. (1915) J. Chem. Soc. 107:702–715

    CAS  Google Scholar 

  • Overkleef H. S., Bos P. R., Hekking B., Gordon E., Ploegh H., Kessler B. (2000) Tetrahedron Lett. 41:6005–6009

    Article  Google Scholar 

  • Pérez-Tomás, R., Montaner-Ramoneda, B., Giralt-Lledó, E., Martinell-Pedemonte, M. and Vilaseca-Casas, M.: 2004, Patent WO 2004/031130

  • Senten K., Daniëls L., Van der Veken P., De Meester I., Lambeir A.-M., Scharpé S., Haemers A., Augustyns K. (2003) J. Comb. Chem. 5:336–344

    Article  PubMed  CAS  Google Scholar 

  • Sheehan J., Ledis L. (1973) J. Am. Chem. Soc. 95:875–879

    Article  PubMed  CAS  Google Scholar 

  • Shemyakin M., Ivanov V., Schelokov V., Shkrob A. (1964) Tetrahedron Lett. 1:47–54

    Article  Google Scholar 

  • Soto-Cerrato V., Montaner B., Martinell M., Vilaseca M., Giralt E., Pérez-Tomás R. (2005) Biochem. Pharmacol. 71:32–41

    Article  PubMed  CAS  Google Scholar 

  • Wang Z., Zhao C., Pierce M., Fortunak J. (1999) Tetrahedron Asymmetry 10:225–228

    Article  CAS  Google Scholar 

  • Wasserman H., Keggi J., McKeon J. (1961) J. Am. Chem. Soc. 83:4107–4018

    Article  CAS  Google Scholar 

  • Wasserman H., Keggi J., McKeon J. (1962) J. Am. Chem. Soc. 84:2978–2982

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Nadine Payrot and Vanya Uzunova for their excellent technical assistance. This work was supported by the Generalitat de Catalunya (CeRBa and Grups Consolidats (2005SGR-00663)), Ministerio de Ciencia y Tecnología (BIO 2005-00295) and Cancer Research Technology Ltd.

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Authors and Affiliations

  1. Institut de Recerca Biomèdica (IRB Barcelona), Parc Científic de Barcelona, Josep Samitier, 1-5, 08028, Barcelona, Spain

    Meritxell Teixidó, Josep Maria Caba, Roger Prades, Esther Zurita, Marc Martinell, Fernando Albericio & Ernest Giralt

  2. Servei d’Espectrometria de Masses, Serveis Cientifico-Tècnics, Universitat de Barcelona, Martí i Franquès, 1, 08028, Barcelona, Spain

    Marta Vilaseca

  3. Departament de Química Orgànica, Universitat de Barcelona, Martí i Franquès, 1, 08028, Barcelona, Spain

    Fernando Albericio & Ernest Giralt

Authors
  1. Meritxell Teixidó
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  2. Josep Maria Caba
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  3. Roger Prades
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  4. Esther Zurita
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  5. Marc Martinell
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  6. Marta Vilaseca
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  7. Fernando Albericio
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  8. Ernest Giralt
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Correspondence to Ernest Giralt.

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Teixidó, M., Caba, J.M., Prades, R. et al. Does the Solid-Phase Synthesis of a Tetrapeptide Represent a Challenge at the Onset of the XXI Century? The Case of Cyclo [(3R)-3-hydroxydecanoyl-l-seryl-(3R)-3-hydroxydecanoyl-l-seryl]. Int J Pept Res Ther 13, 313–327 (2007). https://doi.org/10.1007/s10989-007-9086-z

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