Synthesis of organometallic amines and their coupling to the C-terminus ofamino acids and peptides

This work describes the use of organometallic amines for the labelling of t he C-terminus of amino acids and peptides. N-substituted ferrocene-methylam ines 2 could be readily prepared and coupled to a variety of amino acids in good yield. The novel ferrocene amino acid derivatives 4 exist in two conf ormations in solution, which differ in the orientation of the tertiary amid e bond and interconvert slowly in solution. For the glycine derivative 4a t he activation energy was determined to be 70.3 kJ mol(-1) by H-1-NMR spectr oscopy. All new compounds were completely characterised spectroscopically i ncluding N-15-NMR by indirect detection 2D H-1-N-15-NMR. The potential diff erence of ca. +50 mV between ferrocene derivatives 2 and the ferrocenyl ami no acids 4 in cyclic voltammetry was used to monitor the peptide coupling r eaction in situ. Also described are attempts towards the synthesis of organ ometallic amine derivatives of benzene chromium tricarbonyl and eta-cyclope ntadienyl molybdenum dicarbonyl. The solid state structures of CpMo(CO)(2)- C2H4-N(CO)(2)C6H4 14 and CpFeC5H4-CH2-NH-CH2-p-CH3-C6H4 2a (Cp: eta-cyclope ntadienyl) were determined by single-crystal X-ray diffraction. (C) 1999 El sevier Science S.A. All rights reserved.