Cactuar,
Amino acid chlorides can be made and were extensively used in the early days (pre-1940) of peptide synthesis. The problem was, as you have noted,
finding suitable amine protecting groups stable to acyl chloride formation but easy to remove without ripping apart the newly synthesized peptide.
Protection of the amino group can be done using most any acyl group (eg, benzoyl) or sulfonamide (eg p-tosyl) but these are very difficult to cleanly
remove. Alkoxycarbonyl groups such N-ethoxycarbonyl or Cbz would be more versatile as they are more easily removed than a regular acyl group and can
survive acid chloride formation. You might do well to consult Greenstein and Winitz, "Chemistry of the Amino Acids." Volume 2 has an extensive
discussion of coupling reactions including some information on amino acid chlorides.
AvB |