53793-18-3Relevant academic research and scientific papers
Synthesis of Enantiomerically Pure 5-Substituted Piperazine-2-Acetic Acid Esters as Intermediates for Library Production
Jain, Prashi,Raji, Idris O.,Chamakuri, Srinivas,MacKenzie, Kevin R.,Ebright, Brandon T.,Santini, Conrad,Young, Damian W.
, p. 6040 - 6064 (2019)
The piperazine heterocycle is housed within a large number of FDA-approved drugs and biological probe compounds. Structurally, however, these compounds are mostly confined to substitutions on the two ring nitrogen atoms, rationalizing the expansion of piperazine chemical diversity through carbon substitutions. On the basis of the concept of systematic chemical diversity, a divergent six-step synthesis was developed in which chiral amino acids were transformed, with high diastereoselectivity, into either cis or trans 5-substituted piperazine-2-acetic acid esters that could be chromatographically rendered diastereomerically homogeneous. Starting from six commercially available amino acids or their respective amino alcohols (both antipodes), we obtained a complete set of 24 protected chiral 2,5-disubstituted piperazines, as single stereoisomers in multigram quantities. These diverse and versatile piperazines can be functionalized on either nitrogen atom, allowing them to be used as starting materials for parallel library synthesis and as intermediates for the targeted production of more complex C-substituted piperazine compounds.
Synthesis of Enantiomerically Pure 5-Substituted Piperazine-2-Acetic Acid Esters as Intermediates for Library Production
Jain, Prashi,Raji, Idris O.,Chamakuri, Srinivas,Mackenzie, Kevin R.,Ebright, Brandon T.,Santini, Conrad,Young, Damian W.
, (2019/05/22)
The piperazine heterocycle is housed within a large number of FDA-approved drugs and biological probe compounds. Structurally, however, these compounds are mostly confined to substitutions on the two ring nitrogen atoms, rationalizing the expansion of piperazine chemical diversity through carbon substitutions. On the basis of the concept of systematic chemical diversity, a divergent six-step synthesis was developed in which chiral amino acids were transformed, with high diastereoselectivity, into either cis or trans 5-substituted piperazine-2-acetic acid esters that could be chromatographically rendered diastereomerically homogeneous. Starting from six commercially available amino acids or their respective amino alcohols (both antipodes), we obtained a complete set of 24 protected chiral 2,5-disubstituted piperazines, as single stereoisomers in multigram quantities. These diverse and versatile piperazines can be functionalized on either nitrogen atom, allowing them to be used as starting materials for parallel library synthesis and as intermediates for the targeted production of more complex C-substituted piperazine compounds.
Ready available chiral azapyridinomacrocycles n-oxides; First results as lewis base catalysts in asymmetric allylation of p-nitrobenzaldehyde
Veitia, Maite Sylla-Iyarreta,Joudat, Mounia,Wagner, Mathieu,Falguieres, Annie,Guy, Alain,Ferroud, Clotilde
scheme or table, p. 2011 - 2039 (2011/10/19)
We report here the straightforward synthesis of the first series of enantiomerically pure azapyridinomacrocycles N-oxides containing a cyclohexyl chiral moiety. These compounds were readily obtained in good overall yields by a convergent synthesis using natural amino acids as starting building blocks and macrocyclisation as the key step. This method is rapid, efficient and suitable for the introduction of various substituents at the macrocyclic skeleton. Finally, the compounds were tested as organocatalysts for the enantioselective allylation of p-nitrobenzaldehyde with allyltrichlorosilane.
