Synthesis of stable and radioactive isotope-containing peptidoglycan fragments

In this work, a method for the total synthesis of different isotope-containing mesodiaminopimelic
acids (m-A2pm or (2S,6R)-A2pm) is presented. This compound,
specific of bacterial cell wall, allows for the reticulation of peptidoglycan in most
Gram-negative and some Gram-positive bacteria. A preparation of new isotopecontaining
compounds (1-13C)(2S,6R)-A2pm and (4,5-2H2)(2S,6R)-A2pm is hereby
presented. These compounds can be used as chromatography and quantitative mass
spectrometry references for the study of peptidoglycan dynamics. The first total
stereoselective synthesis of high specific activity (30 Ci/mmol) tritiated
[4,5-3H](2S,6R)-A2pm is also described. Furthermore, the synthesis of differentially
protected (2S,6R)-A2pm and (4,5-2H2)(2S,6R)-A2pm allowed the preparation of
peptidoglycan peptide fragments, which broaden the scope of applications to
studies of b-lactamase induction phenomenon in penicillin resistant bacteria as well
as to studies in the field of human innate immune system.