Acid-labile handles for Fmoc solid-phase synthesis of peptide N-alkylamides

Michael F. Songster, Josef Vagner, George Barany

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

By analogy to established methodology for the preparation of C-terminal peptide amides by 9-fluorenylmethyl-oxycarbonyl (Fmoc) chemistry, in conjunction with the acidolyzable 5-(4-Fmoc-aminomethyl-3,5-dimethoxyphenoxy)valeric acid (PAL, 1) handle, the present paper reports on 5-(4-(N-Fmoc-N-alkyl)aminomethyl-3,5-dimethoxyphenoxy)valeric acid [(R)PAL, 2] handles that can be used for synthesis of peptide N-alkylamides. The key step in the preparation of these handles was the NaBH3CN-mediated reductive amination (60 to 85% yields; R=CH3, CH3CH2, C6H5CH2CH2, 4-NO2C6H5) of 5-(4-formyl-3,5-dimethoxyphenoxy)valeric acid (4), an aldehyde precursor to PAL. The (R)PAL handles (2a and b) were applied to the preparation of LHRH analogues. After anchoring of handles to PEG-PS supports, peptide chain assemblies were carried out, and treatments with TFA-thioanisolephenol-1,2-ethanedithiol (87:5:5:3) for 90 min at 25 °C, followed by aqueous workups, provided the expected products in excellent yields and purities as supported by HPLC and mass spectrometric characterization.

Original languageEnglish (US)
Pages (from-to)265-270
Number of pages6
JournalLetters in Peptide Science
Volume2
Issue number5
DOIs
StatePublished - Jan 1996
Externally publishedYes

Fingerprint

Solid-Phase Synthesis Techniques
Peptides
Acids
Amination
Aldehydes
Amides
Gonadotropin-Releasing Hormone
Polyethylene glycols
High Pressure Liquid Chromatography
n-pentanoic acid

Keywords

  • Acidolyzable anchors
  • LHRH analogues
  • Reductive amination
  • Tris(alkoxybenzyl) N-alkylamides [(R)PAL]

ASJC Scopus subject areas

  • Biochemistry

Cite this

Acid-labile handles for Fmoc solid-phase synthesis of peptide N-alkylamides. / Songster, Michael F.; Vagner, Josef; Barany, George.

In: Letters in Peptide Science, Vol. 2, No. 5, 01.1996, p. 265-270.

Research output: Contribution to journalArticle

Songster, Michael F. ; Vagner, Josef ; Barany, George. / Acid-labile handles for Fmoc solid-phase synthesis of peptide N-alkylamides. In: Letters in Peptide Science. 1996 ; Vol. 2, No. 5. pp. 265-270.
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