Synthesis of functionalized, unsymmetrical 1,3,4,6-tetrasubstituted 2,5-diketopiperazines.
A general and efficient method for the synthesis of unsymmetrical 1,3,4,6-tetrasubstituted 2,5-diketo- piperazines (DKPs) is described. Cyclization of N-amide alkylated dipeptide methyl esters, followed by alkylation, furnished the corresponding tetrasubstituted DKPs in good overall yields. The influence of steric hindrance in the alkylation reactions appeared to be of lesser importance as long as reactive alkylating agents were used. Furthermore, we have demonstrated the use of tetrasubstituted DKPs as a scaffold for further chemical manipulations to produce novel DKPs with desired properties.
Tullberg
Marcus
M
Department of Chemistry, Medicinal Chemistry, Göteborg University, SE-412 96 Göteborg, Sweden.
Grøtli
Morten
M
Luthman
Kristina
K
D000478:Alkylation; D000577:Amides / Q000737:chemistry; D000586:Amination; D000596:Amino Acids / Q000138:chemical synthesis / Q000737:chemistry; D001965:Bromides / Q000737:chemistry; D003500:Cyclization; D054659:Diketopiperazines; D004151:Dipeptides / Q000737:chemistry; D018054:Hydrobromic Acid / Q000737:chemistry; D015394:Molecular Structure; D009584:Nitrogen / Q000737:chemistry; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry*
D000577:Amides; D000596:Amino Acids; D001965:Bromides; D054659:Diketopiperazines; D004151:Dipeptides; D010879:Piperazines; D018054:Hydrobromic Acid; D009584:Nitrogen