Metabolism of Deuterated threo-Dihydroxy Fatty Acids in Saccharomyces cerevisiae: Enantioselective Formation and Characterization of Hydroxylactones and γ-Lactones

✍ Scribed by Leif-A. Garbe; Roland Tressl

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: German
• Weight: 315 KB
• Volume: 87
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.200490007

✦ Synopsis

Abstract

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).