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Carbon‐14 labelling of DIOVAN™ in its valine‐moiety
Author(s) -
Moenius Th.,
Voges R.,
Burtscher P.,
Züger Ch.
Publication year - 2000
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/1099-1344(200011)43:13<1245::aid-jlcr412>3.0.co;2-0
Subject(s) - chemistry , moiety , organic chemistry , valine , amino acid , biochemistry
As a highly specific and non peptide AT 1 ‐antagonist Valsartan 2 is marketed under the tradename DIOVAN™ for effective treatment of hypertension. This paper describes the synthesis of C‐14 labelled Valsartan 2 , which incorporates two C‐14 isotopes in the valine‐moiety. Reaction of (−)‐bromo‐[1,2‐ 14 C]acetyl bornane‐10.2‐sultam 8a ((−)‐[ 14 C 2 ]BABS) with benzophenone imine gave (−)‐diphenyl‐methylene[1,2‐ 14 C 2 ]glycinyl bornane‐10.2‐sultam 9 ((−)‐[ 14 C 2 ]DPMGBS), which was alkylated with 2‐iodopropane to build‐up the valine structure 10 . Initially the resulting sultam‐protected valine 11 was treated with the benzyl bromide 12 to produce the precursor 13 . However, under conditions routinely used for sultam‐cleavage deprotection resulted in the racemization of the amino acid. Successful cleavage was accomplished via N‐Boc‐protection of 11 followed by hydrolytic cleavage of the auxiliary and esterification to give the L‐[ 14 C 2 ]valine benzyl ester 18 . Finally [ 14 C 2 ]Valsartan 2 was synthesised in a 10 step synthesis in an overall radiochemical yield of 10 % relative to the (−)‐[1,2‐ 14 C]BABS 8a employed. Copyright © 2000 John Wiley & Sons, Ltd.