STEREOCONTROLLED SYNTHESIS OF DTPA ANALOGS BRANCHED IN THE ETHYLENE UNIT

Stereochemically controlled synthesis of diethylenetriaminepentaacetic acid (DTPA) analogues substituted on the ethylene backbones with meth yl 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 te rt-butyl glycinate. Attaching the remaining modified alanine (or glyci ne) fragment through acyl coupling and then selective reduction of the amide followed by hydrolysis of the esters afforded the substituted D TPA analogues. Ester differentiation has been accomplished through alk ylation rather than acylation of the (S)-propylenediaminetriacetic aci d triester. A byproduct from this alkylation is the oxazoloisoindole f ormed by internal alkylation of the oxygen of the phthaloyl protecting group. Phthaloyl deprotection followed by dialkylation afforded the e ster-differentiated (S,S)-dipropylenetriaminepentaacetic esters. The e nantiomeric purity of the chiral intermediates (S)-alaninol and (S)-pr opylenediamines were determined by HPLC using epimeric standards.