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Metabolism of Deuterated threo ‐Dihydroxy Fatty Acids in Saccharomyces cerevisiae: Enantioselective Formation and Characterization of Hydroxylactones and γ ‐Lactones
Author(s) -
Garbe LeifA.,
Tressl Roland
Publication year - 2004
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.200490007
Subject(s) - chemistry , stereochemistry , enantioselective synthesis , lactone , saccharomyces cerevisiae , yeast , enantiomer , catalysis , organic chemistry , biochemistry
Biotransformation of (±)‐ threo ‐7,8‐dihydroxy(7,8‐ 2 H 2 )tetradecanoic acids ( threo ‐(7,8‐ 2 H 2 )‐ 3 ) in Saccharomyces cerevisiae afforded 5,6‐dihydroxy(5,6‐ 2 H 2 )dodecanoic acids ( threo ‐(5,6‐ 2 H 2 )‐ 4 ), which were converted to (5 S ,6 S )‐6‐hydroxy(5,6‐ 2 H 2 )dodecano‐5‐lactone ((5 S ,6 S )‐(5,6‐ 2 H 2 )‐ 7 ) with 80% e.e. and (5 S ,6 S )‐5‐hydroxy(5,6‐ 2 H 2 )dodecano‐6‐lactone ((5 S ,6 S )‐5,6‐ 2 H 2 )‐ 8 ). Further β ‐oxidation of threo ‐(5,6‐ 2 H 2 )‐ 4 yielded 3,4‐dihydroxy(3,4‐ 2 H 2 )decanoic acids ( threo ‐(3,4‐ 2 H 2 )‐ 5 ), which were converted to (3 R ,4 R )‐3‐hydroxy(3,4‐ 2 H 2 )decano‐4‐lactone ((3 R ,4 R )‐ 9 ) with 44% e.e. and converted to 2 H‐labeled decano‐4‐lactones ((4 R )‐(3‐ 2 H 1 )‐ and (4 R )‐(2,3‐ 2 H 2 )‐ 6 ) with 96% e.e. These results were confirmed by experiments in which (±)‐ threo ‐3,4‐dihydroxy(3,4‐ 2 H 2 )decanoic acids ( threo ‐(3,4‐ 2 H 2 )‐ 5 ) were incubated with yeast. From incubations of methyl (5 S ,6 S )‐ and (5 R ,6 R )‐5,6‐dihydroxy(5,6‐ 2 H 2 )dodecanoates ((5 S ,6 S )‐ and (5 R ,6 R )‐(5,6‐ 2 H 2 )‐ 4a ), the (5 S ,6 S )‐enantiomer was identified as the precursor of (4 R )‐(3‐ 2 H 1 )‐ and (2,3‐ 2 H 2 )‐ 6 ). Therefore, (4 R )‐ 6 is synthesized from (3 S ,4 S )‐ 5 by an oxidation/keto acid reduction pathway involving hydrogen transfer from C(4) to C(2). In an analogous experiment, methyl (9 S ,10 S )‐9,10‐dihydroxyoctadecanoate ((9 S ,10 S )‐ 10a ) was metabolized to (3 S ,4 S )‐3,4‐dihydroxydodecanoic acid ((3 S ,4 S )‐ 15 ) and converted to (4 R )‐dodecano‐4‐lactone ((4 R )‐ 18 ).