817562-88-2Relevant academic research and scientific papers
Development of a multigram asymmetric synthesis of 2-(R)-2-(4,7,10-tris tert-butylcarboxymethyl-1,4,7,10-tetraazacyclododec-1-yl)-pentanedioic acid, 1-tert-butyl ester, (R)-tert-Bu4-DOTAGA1
Levy, Stuart G.,Jacques, Vincent,Zhou, Kevin Li,Kalogeropoulos, Shirley,Schumacher, Kelly,Amedio, John C.,Scherer, Jonathan E.,Witowski, Steven R.,Lombardy, Richard,Koppetsch, Karsten
, p. 535 - 542 (2009)
A process for the multigram asymmetric synthesis of the chiral tetraazamacrocycle 2-(R)-2-(4,7,10-tris tert-butylcarboxymethyl- 1,4,7,10-tetraazacyclododec-1-yl)-pentanedioic acid, 1-tert-butyl ester ((R)-tert-Bu4-DOTAGA, 4) has been devised and demonstrated. The nine-step synthesis features an improved synthesis of 2-(S)-5- oxotetrahydrofuran- 2-carboxylic acid, tert-butyl ester 8, the precursor to the novel alkylating agent (S)-5-benzyl 1-tert-butyl 2-(methylsulfonyloxy) pentanedioate 12, which was used to introduce an orthogonally protected chiral glutarate arm to the 1,4,7,10-tetraazacyclododecane (cyclen) nucleus in high optical purity. Cyclen derivative (R)-t-Bu4-DOTAGA, 4, a key intermediate for the manufacture of a magnetic resonance imaging (MRI) candidate, was produced with high chemical (≥95%) and optical (ee ≥ 97%) purity. The process developed was successfully applied to the kilogram-scale cGMP synthesis of (R)-t-Bu4-DOTAGA.
Optically pure and enriched isomers of chelating ligands and contrast agents
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Page/Page column 14-16; sheet 2, (2008/06/13)
Organic chelating ligands, organic chelating ligand precursors, and metal chelates are disclosed. Methods for synthesizing the same are also described, including methods for preparing optically-enriched or optically-pure compositions of the same.
