Bioreduction of methyl heteroaryl and aryl heteroaryl ketones in high enantiomeric excess with newly isolated fungal strains.
Enantioenriched heteroaryl ethanols and aryl heteroarylmethanols are important intermediates and structural motifs in medicinal chemistry. Asymmetric biocatalytic reduction of corresponding ketones provides a straightforward approach for preparation of these compounds. Accordingly, three newly isolated fungal strains have been described, which produced the desired heteroaryl alcohols in high enantiomeric excess (ee). A broad substrate specificity was observed within these limited number of biocatalysts as demonstrated by preparation of a variety of heteroaryl alcohols, including (S)-5-(1-hydroxyethyl)furo[2,3-c]pyridine, a key intermediate for HIV-1 reverse transcriptase inhibitor, (S)-phenyl(pyridin-2-yl)methanol, an analgesic and (S,S)-2,6-bis(1-hydroxyethyl)pyridine, a chiral building block, mostly in >99% ee and 80-92% yield. Micro-morphologically, one of the isolate was found to be similar to Penicillium funiculosum. However, its β-tubulin sequence showed only 88% sequence identity with the known β-tubulin sequences of Penicillium. It may, therefore, represent a new species of Penicillium. The other biocatalysts were identified as Alternaria alternata and Talaromyces flavus.
Institute of Microbial Technology (Council of Scientific and Industrial Research), Sector 39, Chandigarh 160036, India.
Mohan
M
Pal
Gautam
G
Srivastava
Lomary S
LS
Moon
Ravinder S
RS
Jolly
D000528:Alternaria / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D055162:Biocatalysis / Q000187:drug effects; D001673:Biodegradation, Environmental / Q000187:drug effects; D005658:Fungi / Q000187:drug effects / Q000302:isolation & purification* / Q000378:metabolism*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors / Q000378:metabolism; D007659:Ketones / Q000737:chemistry* / Q000378:metabolism*; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction / Q000187:drug effects; D010407:Penicillium / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D010802:Phylogeny; D011725:Pyridines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D013237:Stereoisomerism; D013379:Substrate Specificity / Q000187:drug effects; D032901:Talaromyces / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D014404:Tubulin / Q000235:genetics
D007659:Ketones; D011725:Pyridines; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors; D014404:Tubulin; C543930:2-acetylpyridine; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; C111902:PNU 142721