Conversion of nocathiacin I to nocathiacin acid by a mild and selective cleavage of dehydroalanine.
Thiazolyl peptide antibiotic nocathiacin I (1) was converted to nocathiacin acid (4) in high yield by treatment with trifluoroacetic anhydride and pyridine in THF at room temperature. Two equipotent water-soluble amide analogues of nocathiacin I were readily prepared from this important and versatile carboxylic acid intermediate under mild peptide coupling conditions. The present method is useful for chemical derivatization of complex natural products that contain C-terminal dehydroalanine.
Xu
Libo
L
Merck Research Laboratories, Rahway, NJ 07065, USA. libo_xu@merck.com
Farthing
Amy K
AK
Shi
Yao-Jun
YJ
Meinke
Peter T
PT
Liu
Kun
K
D000409:Alanine / Q000031:analogs & derivatives* / Q000737:chemistry; D002264:Carboxylic Acids / Q000138:chemical synthesis*; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000138:chemical synthesis*; D013844:Thiazoles / Q000138:chemical synthesis*
D002264:Carboxylic Acids; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D010456:Peptides, Cyclic; D013844:Thiazoles; C463319:nocathiacin I; C549323:nocathiacin acid; C015102:dehydroalanine; D000409:Alanine