A Practical Large-Scale Synthesis
of Cyclic RGD Pentapeptides Suitable for Further Functionalization
through ‘Click’ Chemistry

Jiří Paleček; Gerald Dräger; Andreas Kirschning

doi:10.1055/s-0030-1258396

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Synthesis 2011(4): 653-661
DOI: 10.1055/s-0030-1258396

PAPER

A Practical Large-Scale Synthesis of Cyclic RGD Pentapeptides Suitable for Further Functionalization through ‘Click’ Chemistry

Jiří Paleček, Gerald Dräger, Andreas Kirschning*
Institut für Organische Chemie and Biomolekulares Wirkstoffzentrum (BMWZ), Leibniz Universität Hannover, Schneiderberg 1b, 30167 Hannover, Germany
e-Mail: andreas.kirschning@oci.uni-hannover.de;

Further Information

Publication History

Received 18 November 2010
Publication Date:
11 January 2011 (online)

Abstract
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Abstract

A multigram batch of the cyclo[Arg-Gly-Asp-d-Phe-Lys] and its N-ε-azido derivative was accomplished via solution-phase synthesis using an epimerization-free fragment condensation. The C-terminus of d-Phe was protected as its tert-butyl ester. Fmoc (Arg, Gly, Asp, d-Phe) and Boc (Lys) groups were used to protect all N-α-termini. The Ts and NO₂ groups, respectively were chosen to protect the guanidine group. The macrocyclization step (between d-Phe and l-Lys) was carried out under TBTU/HOBt or DPPA condensation conditions. Finally, the ε-amino group of the lysine residue was selectively converted into the azido group by a diazo-transfer reaction.

Key words

RGD-peptides - solution-phase synthesis - amino acids - cyclizations - diazo compounds

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