Stereocontrolled Synthesis of DTPA Analogs Branched in the Ethylene Unit

• Published in: Journal of organic chemistry Vol. 60; no. 21; pp. 6987 - 6997
• Main Authors: Grote, Christopher W, Kim, Dong Jin, Rapoport, Henry
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 01.10.1995; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; ROUTE; LIGANDS; CONVERSION; AMINO-ACIDS; SELECTIVE REDUCTIONS; DIETHYLENETRIAMINEPENTAACETIC ACID; AGENTS; DERIVATIVES; BINDING; DIBORANE
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo00126a059

Stereochemically controlled synthesis of diethylenetriaminepentaacetic acid (DTPA) analogues substituted on the ethylene backbones with methyl groups, the chiral center a to the terminal nitrogen being derived from (S)- or (R)-alanine, has been achieved. The key intermediate (S)-propylenediaminetriacetic acid triester was synthesized via selective detosylation of the alkylation product derived from (S)-alanine and tert-butyl glycinate. Attaching the remaining modified alanine (or glycine) fragment through acyl coupling and then selective reduction of the amide followed by hydrolysis of the esters afforded the substituted DTPA analogues. Ester differentiation has been accomplished through alkylation rather than acylation of the (S)-propylenediaminetriacetic acid triester. A byproduct from this alkylation is the oxazoloisoindole formed by internal alkylation of the oxygen of the phthaloyl protecting group. Phthaloyl deprotection followed by dialkylation afforded the ester-differentiated (S,S)-dipropylenetriaminepentaacetic esters. The enantiomeric purity of the chiral intermediates (S)-alaninol and (S)-propylenediamines were determined by HPLC using epimeric standards.