Kani ZILBEYAZ, Namudar İzzet KURBANOĞLU, Esabi Başaran KURBANOĞLU

Production of (S)-2'-fluorophenylethan-1-ol and (S)-3'- fluorophenylethan-1-ol by Alternaria alternata using ram horn peptone in microbial growth medium

Enantiyomerik olarak saf florlu bileşikler tıbbi kimyada önemli bir role sahiptir. Alternaria alternata izolatları (S)- 2'-florofeniletan-1-ol 1b ve (S)-3'-florofeniletan-1-ol 2b’nin sentezinde kullanılmıştır. Optik olarak aktif 1b ve 2b’nin biyokatalitik sentezleri koç boynuz peptonu (KBP) ihtiva eden A. alternata’nın sıvı kültüründe 2'-floroasetopepton 1a ve 3'-floroasetopepton 2a’nın asimetrik indirgenmesiyle başarılmıştır. Substratların dönüşümünü artırmak için pH, sıcaklık ve çalkalama gibi reaksiyon şartları çalışılmıştır. Optimal reaksiyon şartları pH 6,0, çalkalama 250, sıcaklık 32 °C ve substrat 3 mmol/100 mL olarak bulundu. KBP kullanılarak en etkili biyokatalist A. alternata EBK-6 tarafından 1b ve 2b’nin gram miktarda üretimleri 1 L çalışma hacmine sahip fermentörde gerçekleştirilmiştir. Sonuçlar hem 1b ve hem de 2b’nin % 99 enantiyomerik selektivite (es) ile verimleri 1b için % 75 ve 2b için % 66’ya ulaştığını göstermiştir. Fermentasyon sonunda 1b ve 2b ürünlerinin konsantrasyonları sırasıyla 3,1 g/L ve 2,8 g/L olarak bulunmuştur. Sonuç olarak, atık materyalden üretilen KBP ihtiva eden sıvı kültürde A. alternata EBK-6 kullanımıyla ilaç endüstrisi için iki önemli kiral bileşik mükemmel es ile gram miktara kadar üretilmiştir.

Mikrobiyal üreme ortamında koç boynuz peptonu kullanılarak Alternaria alternata tarafından (S)-2'-florofeniletan-1-ol ve (S)-3'-florofeniletan-1-ol üretimi

Enantiomerically pure, fluorinated compounds have an important role in medicinal chemistry. Alternaria alternata isolates were used for the synthesis of (S)-2'-fluorophenylethan-1-ol 1b and (S)-3'-fluorophenylethan-1-ol 2b. Biocatalytic syntheses of optically active 1b and 2b were achieved by asymmetric reduction of 2'-fluoroacetophenone 1a and 3'-fluoroacetophenone 2a in the batch culture of A. alternata containing ram horn peptone (RHP). The reaction conditions (pH, temperature, and agitation) that improve the conversion of the substrates were studied. The optimal reaction conditions were found as pH 6.0, agitation 250, temperature 32 °C and substrate 3 mmol/100 mL. The gram scale productions of 1b and 2b by the most effective biocatalyst A. alternata EBK-6 using RHP was carried out in a fermenter with 1-L working volume. The results showed that the yields with >99% enantiomeric excess (ee) of both 1b and 2b reached 75% for 1b and 66% for 2b. The concentrations of products 1b and 2b at the end of fermentation were 3.1 g/L and 2.8 g/L, respectively. As a result, 2 important chiral intermediates for the pharmaceutical industry using A. alternata EBK-6 in the submerged culture containing RHP from waste material were scaled up to gram scale with excellent ee.

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