Bio-catalytic asymmetric synthesis of beta-adrenergic receptor blocker precursor: (R)-2-bromo-1-(naphthalen-2-yl)ethanol

Taşdemir V., Kalay E., DERTLİ E., Sahin E.

BIOCATALYSIS AND BIOTRANSFORMATION, cilt.38, sa.6, ss.438-444, 2020 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 38 Sayı: 6
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1080/10242422.2020.1768245
  • Dergi Adı: BIOCATALYSIS AND BIOTRANSFORMATION
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, Compendex, EMBASE, Environment Index, Food Science & Technology Abstracts
  • Sayfa Sayıları: ss.438-444
  • Anahtar Kelimeler: Chiral 2-haloethanols, biocatalysts, asymmetric reduction, (R)-2-bromo-1-(naphthalen-2-yl)ethanol, Lactobacillus curvatus, BETA(2)-ADRENOCEPTOR AGONISTS, TRANSFER HYDROGENATION, CARBONYL REDUCTASE, KETONES, HYDRATION
  • Yıldız Teknik Üniversitesi Adresli: Evet

Özet

Aromatic alpha-halohydrins, particularly 2-haloethanols as significant precursor of drugs, can easily be converted to chiral beta-adrenergic receptor blockers. Eight strains of Lactobacillus curvatus were tested as biocatalysts for asymmetric reduction of 2-bromo-1-(naphthalen-2-yl)ethanone 1 to 2-bromo-1- (naphthalen-2-yl) ethanol 2. The parameters of the bioreduction were optimized using L. curvatus N4, the best biocatalyst found. As a result, (R)-2-bromo-1-(naphthalen-2-yl)ethanol 2, which can be beta-adrenergic receptor blocker precursor, was produced for the first time in high yield and enantiomerically pure form using biocatalysts. Moreover, the gram scale synthesis was performed and 7.54 g of (R)-2 was synthesized as enantiopure form (enantiomeric excess >99%) in 48 h. The important advantages of this process are that it produces of (R)-2 for the first time in enantiopure form, in excellent yield and under environmentally friendly and moderate reaction conditions. This system is of the potential to be applied at a commercial scale.