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Efficient synthesis of enantiomerically pure thioester precursors of [ 11 C]McN‐5652 from racemic McN‐5652
Author(s) -
Zessin J.,
Gucker P.,
Ametamey S. M.,
Steinbach J.,
Brust P.,
Vollenweider F. X.,
Johannsen B.,
Schubiger P. A.
Publication year - 1999
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/(sici)1099-1344(19991230)42:13<1301::aid-jlcr298>3.0.co;2-2
Subject(s) - chemistry , racemization , enantiomer , demethylation , diastereomer , thioester , isomerization , yield (engineering) , stereochemistry , organic chemistry , enzyme , biochemistry , metallurgy , dna methylation , gene , catalysis , gene expression , materials science
An improved synthesis of the anantiomerically pure thioester precursors of [ 11 C](+)‐McN‐5652 ([ 11 C](+)− 1 ]), and [ 11 C](−)‐McN5652 ([ 11 C](−)− 1 ]) starting from racemic McN‐5652 ((±)− 1 ) is described. The synthetic method includes the resolution of (±)− 1 by repeated crystallization of the (+)‐ and (−)‐di‐p‐toluoyltartrates yielding (+)‐McN‐5652 ((+)− 1 ) and (−)‐McN‐5652 ((−)‐ 1 ), each with >98% enantiomeric purity. S‐Demethylation of (±)− 1 , (+)− 1 , and (−)‐ 1 , respectively was achieved by treatment with sodium amide at low temperatures (−78°C) followed by conversion of the intermediate thiols 2 with acetyl chloride to give the corresponding thioester precursors (±)− 3 , (+)− 3 or (−)− 3 . This demethylation method almost completely suppressed the isomerization of the pharmacologically active trans diastereomer into the inactive cis form. Chiral HPLC analyses confirmed that the S‐demethylation proceeded without any racemization. 11 C‐Labelling of (+)− 3 or (−)− 3 , yields enantiomerically pure [ 11 C](+)‐McN‐5652 or [ 11 C](−)‐McN5652, each in 22% radiochemical yield (decay‐corrected, related to [ 11 C]CO 2 ) and a specific radioactivity of 74 GBq/μmol (2 Ci/μmol) at the end of synthesis (EOS) Copyright © 1999 John Wiley & Sons, Ltd.