Synthesis of Functionalized, Unsymmetrical 1,3,4,6-Tetrasubstituted 2,5-Diketopiperazines

Abstract

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.

Convenient asymmetric synthesis of 1,3,4,6-tetrasubstituted 2,5-diketopiperazines

“…Furthermore, the syntheses of tetrasubstituted diketopiperazines require either multistep sequences or harsh conditions and they are inefficient for asymmetric synthesis. [7][8][9][10][11][12][13] As an extension of our previous work on the asymmetric preparation of 3,4,6-trisubstituted 2,5-diketopiperazines, 14 we herein report a mild and versatile synthetic method for the asymmetric synthesis of 1,3,4,6-tetrasubstituted 2,5-diketopiperazines via one-pot substitution-cyclization of α-bromo tertiary acetamides ( Figure 1). access to diverse highly functionalized diketopiperazines.…”

Mastering chiral substituted 2-oxopiperazines

“…1,2 Moreover, piperazine ring systems are the key structural elements in a vast array of natural products as well as being a large class of biologically active compounds. Examples include indinavir 1, an HIV-protease inhibitor, 3 glivec 2, a potent antiproliferative agent, 4 several compounds acting at receptors in the CNS such as arylpiperazines, powerful 5-HT 1 ligands, 5-7 lemonomycin 3, 8,9 ecteinascidin 743 4, 10 TAN-1251A 5, 11 and dragmacidins B and C 6-7 12 (Fig.…”

A novel and simple synthetic route for a piperazine derivative

“…[1][2][3][4][5][6][7][8][9][10][11] Also some of these species have been recently probed to be versatile as a probe for crystal structure. For instance, the propensity to form macromolecular arrays in the solid state enables the formation of planar or non-planar type structures.…”