Preparation of functionalized, conformationally constrained DTPA analogues from L- or D-serine and trans-4-hydroxy-L-proline. Hydroxymethyl substituents on the central acetic acid and on the backbone.
The enantio- and diastereospecific syntheses of conformationally constrained diethylenetriaminepentaacetic acid (DTPA) analogues that are functionalized with a hydroxymethyl linker substituent on the central acetic acid or on the backbone are described. Key synthetic steps include (i) displacement of the 4-hydroxyl group of N-BOC-trans-4-hydroxy-L-proline benzyl ester, via activation as the triflate, with suitable amines derived from L- or D-serine, (ii) the low-temperature alkylation of diethylenetriamines with the triflate of benzyl glycolate, thereby minimizing competitive lactamization, to give DTPA pentabenzyl esters, and (iii) deprotection to afford the corresponding DTPA analogues under very mild hydrogenolysis conditions.
Pickersgill
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Department of Chemistry, University of California, Berkeley, California 94720, USA.
Rapoport
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D019342:Acetic Acid; D006909:Hydroxyproline; D007202:Indicators and Reagents; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D012694:Serine; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D007202:Indicators and Reagents; D012694:Serine; D004369:Pentetic Acid; D019342:Acetic Acid; D006909:Hydroxyproline