论文信息 - Carbon-14 labelling of DIOVAN™ in its valine-moiety

Carbon-14 labelling of DIOVAN™ in its valine-moiety

As a highly specific and non peptide AT1-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-[1,2-14C]acetyl bornane-10.2-sultam 8a ((−)-[14C2]BABS) with benzophenone imine gave (−)-diphenyl-methylene[1,2-14C2]glycinyl bornane-10.2-sultam 9 ((−)-[14C2]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-[14C2]valine benzyl ester 18. Finally [14C2]Valsartan 2 was synthesised in a 10 step synthesis in an overall radiochemical yield of 10 % relative to the (−)-[1,2-14C]BABS 8a employed. Copyright © 2000 John Wiley & Sons, Ltd.

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