Phosphate Prodrugs for Amines Utilizing a Fast Intramolecular Hydroxy Amide Lactonization

Autor:	Michalis G. Nicolaou, Chong-Sheng Yuan, Ronald T. Borchardt
Rok vydání:	1996
Předmět:	chemistry.chemical_classification Chemistry Hydrochloride Stereochemistry Carboxylic acid Organic Chemistry Peptide Prodrug Phosphate Amino acid chemistry.chemical_compound Amide Organic chemistry Amine gas treating
Zdroj:	The Journal of Organic Chemistry. 61:8636-8641
ISSN:	1520-6904 0022-3263
DOI:	10.1021/jo961477p
Popis:	A novel phosphate prodrug system for amines, amino acids, peptides, and peptide mimetics, which utilizes a fast hydroxy amide lactonization of a 3-(2‘-hydroxy-4‘,6‘-dimethylphenyl)-3,3-dimethylpropionic amide system, was developed. Prodrugs of five model amine/amino acids, including p-anisidine, GlyOMe, PheOMe, LysOMe, and Asp-α-OMe, were synthesized. The syntheses of these model phosphate prodrugs were accomplished by coupling the amine or the protected amino acids with 3-[2‘-(dibenzylphosphono)oxy-4‘,6‘-dimethylphenyl]-3,3-dimethylpropionic acid using coupling agents such as bis(2-oxo-3-oxazolidinyl)phosphinic chloride and 1-(3-dimethylamino)propyl)-3-ethylcarbodiimide hydrochloride, followed by hydrogenolysis. These phosphate prodrugs were evaluated as substrates for the human placental alkaline phosphatase (AP). The structural features of the amine/amino acids attached to the carboxylic acid group of the promoiety were not found to significantly affect the substrate activity for AP, as evidenced by th...
Databáze:	OpenAIRE
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