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The synthesis of carbon‐14 labeled pravastatin
Author(s) -
Wallace M. A.,
Dean D. C.,
Ellsworth R. L.,
Melillo D. G.,
Marks T.,
White R. F.
Publication year - 1993
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/jlcr.2580330804
Subject(s) - chemistry , diastereomer , acylation , hydroxylation , biotransformation , alcohol , organic chemistry , side chain , walden inversion , pravastatin , stereochemistry , medicinal chemistry , catalysis , enzyme , biochemistry , cholesterol , polymer
As asymmetric route to [ 14 C]β‐hydroxycompactin 1 bearing the ( S )‐2‐methyl‐[1‐ 14 C]butanoate side chain has been developed. Methylation of [N‐[1‐ 14 C]butyryl‐4‐( S )‐phenylmethyl‐2‐oxazolidinone 4 afforded a 95:5 mixture of diastereomeric [N‐( S,R )‐2‐methyl‐[1‐ 14 C]butyryl]‐4‐( S )‐phenylmethyl‐2‐oxazolidinones 5,6 which were separated by preparative HPLC. Oxidative cleavage of 5 afforded optically pure ( S )‐2‐methyl‐[1‐ 14 C]butanoic acid. Acylation of alcohol 9 with optically pure ( S )‐2‐methyl‐[1] 14 C]butyryl chloride afforded ester 10 . Removal of the silyl either produced diastereomerically pure compactin 11 . Hydroxylation was carried out by biotransformation with Mucor hiemelus to afford diastereomerically pure [[1‐ 14 C]butanoate]β‐hydroxycompactin, [ 14 C]Pravastatin 1 .