Yeni bir kompozit tasarım tabanlı optimizasyon stratejisi kullanarak enantiyosaf (S)-(4-klorofenil) (fenil) metanol'ün biyokatalitik sentezi
Küçük Resim Yok
Tarih
2024
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Bayburt Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Sentetik organik kimyada, kiral sekonder alkollerin üretimi için biyokatalitik asimetrik indirgemeler önemli bir yere sahiptir. L- kloprastin ve karbinoksaminin gibi ilaçların öncüsü olan (S)-(4- klorofenil) (fenil)metanol ((S)-2)'nin sentezi, yetersiz substrat miktarı ve üretim sürecinde yaşanan çeşitli zorluklar nedeniyle hala önemli eksiklikler içermektedir. Bu tez kapsamında, Lactobacillus paracasei BD101 biyokatalizörü ve yeni bir kompozit tasarım tabanlı optimizasyon tekniği kullanılarak (4-klorofenil) (fenil) metanon (1)'den (S)-2'nin sentezlenmesi hedeflenmiştir. Reaksiyonun optimizasyon koşulları, yeni tasarıma dayalı optimizasyon stratejisi ile şu şekilde belirlendi: pH=5.85, sıcaklık=37 oC, inkübasyon süresi=71 saat ve çalkalama hızı=120 rpm. Ayrıca, reaksiyon dönüşümü %97 ve enantiyomerik fazlalığın (ee) %99 olacağı tahmin edilmiştir. Önerilen optimize edilmiş koşullar altında gerçekleştirilen deneysel çalışmada (S)-2 >%99 ee , >%99 dönüşüm ve %97 verimle elde edildi. Ayrıca, 15.166 g 1, yüksek gram ölçeğinde tamamen (S)-2'ye (14.85 g, %97 saflaştırılmış verim) dönüştürüldü. (S)-2'nin bir biyokatalizör kullanılarak ve tepkime koşullarının kompozit tasarım tabanlı optimizasyon tekniği kullanılarak optimize edilmesi ile gram ölçeğinde üretimi ilk kez bu çalışmada gösterilmiştir. Antitussif (öksürük önleyici) ve antiemetik (kusma önleyici) özelliklere sahip olan ve bronşiyal kasları gevşeten L- kloprastin ve karbinoksamin öncüsü olan (S)-2'nin biyokatalitik sentezi için etkili bir biyokatalitik süreç, kompozit tasarıma dayalı optimizasyon yöntemiyle gösterilmiştir. Ayrıca, biyokatalitik reaksiyonlarda kullanılabilmesi için yeni bir kompozit tasarım tabanlı optimizasyon yönteminin uygulanabilirliği kanıtlanmıştır.
In synthetic organic chemistry, biocatalytic asymmetric reductions have an important place for the production of chiral secondary alcohols. The synthesis of (S)-(4-chlorophenyl) (phenyl)methanol ((S)-2), which is the precursor of drugs such as L-cloprastine and carbinoxamine, still has significant deficiencies due to the insufficient amount of substrate and various difficulties experienced in the production process. In this thesis, it is aimed to synthesize (S)-2 from (4-chlorophenyl) (phenyl) methanone (1) using Lactobacillus paracasei BD101 biocatalyst and a new composite design-based optimization technique. The optimization conditions of the reaction were determined by the new design-based optimization strategy as follows: pH = 5.85, temperature = 37 o C, incubation time = 71 hours and shaking speed = 120 rpm. Additionally, the reaction conversion was estimated to be 97% and the enantiomeric excess (ee) to be 99%. In the experimental study carried out under specified optimized conditions, (S)-2 was obtained with >99% ee, >99% conversion and 97% yield. Additionally, 15.166 g of 1 was completely converted to (S)-2 (14.85 g, 97% purified yield) on a high gram scale. (S)-2 on a gram scale by using a biocatalyst and optimizing the reaction conditions using a composite design-based optimization technique. Its production is shown for the first time in this study. An effective biocatalytic process for the biocatalytic synthesis of (S)-2, a precursor of L- cloprastin and carbinoxamine, which has antitussive (anti-cough) and anti-emetic (anti-vomiting) properties and relaxes bronchial muscles, has been demonstrated by a composite design-based optimization method. In addition, the feasibility of a new composite design-based optimization method for applicability in biocatalytic reactions has been demonstrated.
In synthetic organic chemistry, biocatalytic asymmetric reductions have an important place for the production of chiral secondary alcohols. The synthesis of (S)-(4-chlorophenyl) (phenyl)methanol ((S)-2), which is the precursor of drugs such as L-cloprastine and carbinoxamine, still has significant deficiencies due to the insufficient amount of substrate and various difficulties experienced in the production process. In this thesis, it is aimed to synthesize (S)-2 from (4-chlorophenyl) (phenyl) methanone (1) using Lactobacillus paracasei BD101 biocatalyst and a new composite design-based optimization technique. The optimization conditions of the reaction were determined by the new design-based optimization strategy as follows: pH = 5.85, temperature = 37 o C, incubation time = 71 hours and shaking speed = 120 rpm. Additionally, the reaction conversion was estimated to be 97% and the enantiomeric excess (ee) to be 99%. In the experimental study carried out under specified optimized conditions, (S)-2 was obtained with >99% ee, >99% conversion and 97% yield. Additionally, 15.166 g of 1 was completely converted to (S)-2 (14.85 g, 97% purified yield) on a high gram scale. (S)-2 on a gram scale by using a biocatalyst and optimizing the reaction conditions using a composite design-based optimization technique. Its production is shown for the first time in this study. An effective biocatalytic process for the biocatalytic synthesis of (S)-2, a precursor of L- cloprastin and carbinoxamine, which has antitussive (anti-cough) and anti-emetic (anti-vomiting) properties and relaxes bronchial muscles, has been demonstrated by a composite design-based optimization method. In addition, the feasibility of a new composite design-based optimization method for applicability in biocatalytic reactions has been demonstrated.
Açıklama
Anahtar Kelimeler
Kimya, Chemistry
