A convenient general method for synthesis of N alpha- or N omega-dithiasuccinoyl (Dts) amino acids and dipeptides: application of polyethylene glycol as a carrier for functional purification.
N alpha-Dithiasuccinoyl (Dts) amino acids needed for solid-phase peptide synthesis have been prepared in good yields and excellent purities by a new method that exploits the solubility properties of polyethylene glycol (PEG; bifunctional with average molecular weight 2000 was found to be optimal). Suitably side-chain protected amino acid derivatives are first reacted with a polymeric xanthate, following which the free alpha-carboxyl is blocked by silylation and the Dts heterocycle is elaborated in the same pot by reaction with chlorocarbonylsulfenyl chloride. Upon aqueous work-up, the polymeric carrier removes any urethane blocked amino acids which arise during the process. Exaggerated conditions were explored to prove the power of this functional purification approach, and mechanisms of formation of polymer-bound urethanes are proposed and supported by solution model studies. The preparation and characterization of the companion N-(iso-propyldithio)carbonyl derivative of proline is also presented.
Department of Chemistry, University of Minnesota, Minneapolis.
S
S
Zalipsky
F
F
Albericio
U
U
Słomczyńska
G
G
Barany
D000596:Amino Acids / Q000138:chemical synthesis*; D004151:Dipeptides / Q000138:chemical synthesis*; D006571:Heterocyclic Compounds; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008722:Methods; D010455:Peptides / Q000138:chemical synthesis*; D013388:Succinimides
D000596:Amino Acids; D004151:Dipeptides; D006571:Heterocyclic Compounds; D007202:Indicators and Reagents; D010455:Peptides; D013388:Succinimides