Metabolism of Deuterated Isomeric 6,7-Dihydroxydodecanoic Acids in Saccharomyces cerevisiae – Diastereo- and Enantioselective Formation and Characterization of 5-Hydroxydecano-4-lactone (=4,5-Dihydro-5-(1-hydroxyhexyl)furan-2(3H)-one) Isomers
✍ Scribed by Leif-A. Garbe; Roland Tressl
- Publisher
- John Wiley and Sons
- Year
- 2003
- Tongue
- German
- Weight
- 246 KB
- Volume
- 86
- Category
- Article
- ISSN
- 0018-019X
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✦ Synopsis
Abstract
The chemical synthesis of deuterated isomeric 6,7‐dihydroxydodecanoic acid methyl esters 1 and the subsequent metabolism of esters 1 and the corresponding acids 1a in liquid cultures of the yeast Saccharomyces cerevisiae was investigated. Incubation experiments with (6__R__,7__R__)‐ or (6__S__,7__S__)‐6,7‐dihydroxy(6,7‐^2^H~2~)dodecanoic acid methyl ester ((6__R__,7__R__)‐ or (6__S__,7__S__)‐(6,7‐^2^H~2~)‐1, resp.) and (±)‐threo‐ or (±)‐erythro‐6,7‐dihydroxy(6,7‐^2^H~2~)dodecanoic acid ((±)‐threo‐ or (±)‐erythro‐(6,7‐^2^H~2~)‐1a, resp.) elucidated their metabolic pathway in yeast (Tables 1–3). The main products were isomeric ^2^H‐labeled 5‐hydroxydecano‐4‐lactones 2. The absolute configuration of the four isomeric lactones 2 was assigned by chemical synthesis via Sharpless asymmetric dihydroxylation and chiral gas chromatography (Lipodex ^®^ E). The enantiomers of threo‐2 were separated without derivatization on Lipodex ^®^ E; in contrast, the enantiomers of erythro‐2 could be separated only after transformation to their 5‐O‐(trifluoroacetyl) derivatives. Biotransformation of the methyl ester (6__R,7__R)‐(6,7‐^2^H~2~)‐1 led to (4__R__,5__R__)‐ and (4__S__,5__R__)‐(2,5‐^2^H~2~)‐2 (ratio ca. 4 : 1; Table 2). Estimation of the label content and position of (4__S__,5__R__)‐(2,5‐^2^H~2~)‐2 showed 95% label at C(5), 68% label at C(2), and no ^2^H at C(4) (Table 2). Therefore, oxidation and subsequent reduction with inversion at C(4) of 4,5‐dihydroxydecanoic acid and transfer of ^2^H from C(4) to C(2) is postulated. The 5‐hydroxydecano‐4‐lactones 2 are of biochemical importance: during the fermentation of Streptomyces griseus, (4__S__,5__R__)‐2, known as L‐factor, occurs temporarily before the antibiotic production, and (−)‐muricatacin (=(4__R__,5__R__)‐5‐hydroxy‐heptadecano‐4‐lactone), a homologue of (4__R__,5__R__)‐2, is an anticancer agent.