Synthesis of 1,3-diacylaminopropan-2-ols and corresponding 2-acyl derivatives as amide isosteres of natural lipids.
N,N'-diacyl-1,3-diaminopropan-2-ols as amide isosteres of 1,3-diacylglycerols are obtained in 50-79% yields by treatment of 1,3-diaminopropan-2-ol with acid chlorides either in ether or THF in the presence of triethylamine and catalytic amounts of 4-dimethyl-aminopyridine. Subsequent acylation of the secondary alcohol function with a variety of carboxylic acids (e.g. fatty acids, N-protected amino acids, drug compounds) can be effected by various techniques (i.e. acid chlorides, symmetrical anhydrides, isopropenyl chloroformate) with yields ranging from 56% to 76%.
Mergen
F
F
Department of Medicinal Chemistry, School of Pharmacy, Catholic University of Louvain, Brussels, Belgium.
Lambert
D M
DM
Poupaert
J H
JH
Bidaine
A
A
Dumont
P
P
D000215:Acylation; D000577:Amides / Q000737:chemistry; D004075:Diglycerides / Q000737:chemistry*; D007536:Isomerism; D008055:Lipids / Q000737:chemistry*; D011412:Propanolamines / Q000737:chemistry
D000577:Amides; D004075:Diglycerides; D008055:Lipids; D011412:Propanolamines; C034448:2-aminopropanol