Synthesis of a Homologous Series
of Side-Chain-Extended Orthogonally Protected Aminooxy-Containing
Amino Acids

Fa Liu; Joshua Thomas; Terrence R. Burke Jr.

doi:10.1055/s-2008-1078600

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Synthesis 2008(15): 2432-2438
DOI: 10.1055/s-2008-1078600

PAPER

Synthesis of a Homologous Series of Side-Chain-Extended Orthogonally Protected Aminooxy-Containing Amino Acids

Fa Liu, Joshua Thomas, Terrence R. Burke Jr.*
Laboratory of Medicinal Chemistry, CCR, NCI-Frederick, NIH, Bldg. 376, 1050 Boyles St., Frederick, MD 21702, USA
Fax: +1(301)8466033; e-Mail: tburke@helix.nih.gov;

Further Information

Publication History

Received 21 March 2008
Publication Date:
17 July 2008 (online)

Abstract
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Abstract

Practical methodology is reported for the synthesis of a homologous series of side-chain-extended amino acids containing aminooxy functionality bearing orthogonal protection suitable for Fmoc peptide synthesis. These reagents may be useful for the preparation of libraries containing fragments joined by peptide linkers.

Key words

oxime - peptidomimetic - aldehydes - combinatorial chemistry

References

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13

Available from Novabiochem, Inc.

17

The major fraction obtained by HPLC purification of the peptide resulting using 1a to replace the Thr residue, provided a mass spectral molecular ion (m/z = 1422.4) that was 31 amu lower than expected for the correct product
(m/z = 1453.5). This is consistent with β-elimination of HONH₂ followed by reduction of the resulting double bond during under the reducing conditions of resin cleavage using triethylsilane.

18

The major fraction obtained by HPLC purification of the peptide resulting from the use of 2a to replace the Thr residue, provided mass spectral molecular ions consistent with the desired peptide product [m/z = 1454.5, (M + H) and 1476.5 (M + Na)].