Synthesis of an actinomycin-related peptide lactone from the corresponding cyclic pentapeptide by N,O-acyl shift.
The N,O-acyl shift was investigated as a method for the synthesis of an O-peptide or peptide lactone from a linear or cyclic peptide respectively. Protected derivatives of glycyl-L-threonine could be converted to O-peptides by the action of HCl/dioxane at room temperature and N-acylated under conditions which precluded a reverse O,N-acyl shift. For effecting N,O-acyl shift in cyclo(Thr-D-Val-Pro-Sar-MeAla) this reagent was unsatisfactory and p-toluenesulfonic acid in dioxane at 80 degrees was used instead. The resulting crystalline peptide lactone p-toluenesulfonate salt was N-acylated with 3-benzyloxy-4-methyl-2-nitrobenzoyl chloride to afford a known intermediate in the synthesis of 5,5'-MeAla actinomycin D. This approach constitutes a novel synthetic route to actinomycins and potentially to other peptide lactone antibiotics.
Mauger
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Medlantic Research Foundation, Washington, D.C.
Stuart
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OA
D000215:Acylation; D000595:Amino Acid Sequence; D001671:Biochemistry / Q000379:methods; D055598:Chemical Phenomena; D002621:Chemistry; D002625:Chemistry, Organic / Q000379:methods; D003609:Dactinomycin / Q000031:analogs & derivatives*; D004151:Dipeptides / Q000138:chemical synthesis; D007783:Lactones / Q000138:chemical synthesis*; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis*; D010456:Peptides, Cyclic
D004151:Dipeptides; D007783:Lactones; D010455:Peptides; D010456:Peptides, Cyclic; D003609:Dactinomycin; C061951:glycyl-threonine