20989-17-7Relevant articles and documents
Enantioselective liquid-liquid extraction of (R,S)-phenylglycinol using a bisnaphthyl phosphoric acid derivative as chiral extractant
Schuur, Boelo,Verkuijl, Bastiaan J.V.,Bokhove, Jeroen,Minnaard, Adriaan J.,De Vries, Johannes G.,Heeres, Hero J.,Feringa, Ben L.
, p. 462 - 470 (2011)
This study demonstrates that enantioseparation by liquid-liquid extraction can be done in a continuous flow mode on both laboratory and industrial scale and is a promising technique that could become a competitive alternative for crystallization or chromatographic approaches. We studied the enantioselective liquid-liquid extraction of phenylglycinol (Pgl) using a bisnaphthyl phosphoric acid extractant. Batch experiments were performed to estimate extraction model parameters. The system was described using an extraction mechanism with homogeneous organic phase complexation. The complexation constants were very large, in the order of 108-1010 L/mol in the temperature range 279T303 K. The developed model was then used to design a multistage countercurrent extraction process with Centrifugal Contactor Separator (CCS) equipment. This study demonstrates that high purity (70% ee) with a reasonable yield (36%) can be obtained for a moderately selective system (α=1.7) with only six extraction stages. The technology is potentially applicable to a wide range of racemates. Copyright
Construction and activity evaluation of novel dual-target (SE/CYP51) anti-fungal agents containing amide naphthyl structure
An, Yunfei,Fan, Haiyan,Han, Jun,Liu, Wenxia,Liu, Yating,Sun, Bin,Sun, Zhuang
, (2021/11/16)
With the increase of fungal infection and drug resistance, it is becoming an urgent task to discover the highly effective antifungal drugs. In the study, we selected the key ergosterol bio-synthetic enzymes (Squalene epoxidase, SE; 14 α-demethylase, CYP51) as dual-target receptors to guide the construction of novel antifungal compounds, which could achieve the purpose of improving drug efficacy and reducing drug-resistance. Three different series of amide naphthyl compounds were generated through the method of skeleton growth, and their corresponding target products were synthesized. Most of compounds displayed the obvious biological activity against different Candida spp. and Aspergillus fumigatus. Among of them, target compounds 14a-2 and 20b-2 not only possessed the excellent broad-spectrum anti-fungal activity (MIC50, 0.125–2 μg/mL), but also maintained the anti-drug-resistant fungal activity (MIC50, 1–4 μg/mL). Preliminary mechanism study revealed the compounds (14a-2, 20b-2) could block the bio-synthetic pathway of ergosterol by inhibiting the dual-target (SE/CYP51) activity, and this finally caused the cleavage and death of fungal cells. In addition, we also discovered that compounds 14a-2 and 20b-2 with low toxic and side effects could exert the excellent therapeutic effect in mice model of fungal infection, which was worthy for further in-depth study.
Enantioselective Cascade Biocatalysis for Deracemization of Racemic β-Amino Alcohols to Enantiopure (S)-β-Amino Alcohols by Employing Cyclohexylamine Oxidase and ω-Transaminase
Zhang, Jian-Dong,Chang, Ya-Wen,Dong, Rui,Yang, Xiao-Xiao,Gao, Li-Li,Li, Jing,Huang, Shuang-Ping,Guo, Xing-Mei,Zhang, Chao-Feng,Chang, Hong-Hong
, p. 124 - 128 (2020/09/21)
Optically active β-amino alcohols are very useful chiral intermediates frequently used in the preparation of pharmaceutically active substances. Here, a novel cyclohexylamine oxidase (ArCHAO) was identified from the genome sequence of Arthrobacter sp. TYUT010-15 with the R-stereoselective deamination activity of β-amino alcohol. ArCHAO was cloned and successfully expressed in E. coli BL21, purified and characterized. Substrate-specific analysis revealed that ArCHAO has high activity (4.15 to 6.34 U mg?1 protein) and excellent enantioselectivity toward the tested β-amino alcohols. By using purified ArCHAO, a wide range of racemic β-amino alcohols were resolved, (S)-β-amino alcohols were obtained in >99 % ee. Deracemization of racemic β-amino alcohols was conducted by ArCHAO-catalyzed enantioselective deamination and transaminase-catalyzed enantioselective amination to afford (S)-β-amino alcohols in excellent conversion (78–94 %) and enantiomeric excess (>99 %). Preparative-scale deracemization was carried out with 50 mM (6.859 g L?1) racemic 2-amino-2-phenylethanol, (S)-2-amino-2-phenylethanol was obtained in 75 % isolated yield and >99 % ee.