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.
Bioproduction of Enantiopure (R)- and (S)-2-Phenylglycinols from Styrenes and Renewable Feedstocks
Sekar, Balaji Sundara,Mao, Jiwei,Lukito, Benedict Ryan,Wang, Zilong,Li, Zhi
, p. 1892 - 1903 (2020/12/22)
Enantiopure (R)- and (S)-2-phenylglycinols are important chiral building blocks for pharmaceutical manufacturing. Several chemical and enzymatic methods for their synthesis were reported, either involving multi-step synthesis or starting from a relatively complex chemical. Here, we developed one-pot simple syntheses of enantiopure (R)- and (S)-2-phenylglycinols from cheap starting materials and renewable feedstocks. Enzyme cascades consisting of epoxidation-hydrolysis-oxidation-transamination were developed to convert styrene 2 a to (R)- and (S)-2-phenylglycinol 1 a, with butanediol dehydrogenase for alcohol oxidation as well as BmTA and NfTA for (R)- and (S)-enantioselective transamination, respectively. The engineered E. coli strains expressing the cascades produced 1015 mg/L (R)-1 a in >99% ee and 315 mg/L (S)-1 a in 91% ee, respectively, from styrene 2 a. The same cascade also converted substituted styrenes 2 b–k and indene 2 l into substituted (R)-phenylglycinols 1 b–k and (1R, 2R)-1-amino-2-indanol 1 l in 95–>99% ee. To transform bio-based L-phenylalanine 6 to (R)-1 a and (S)-1 a, (R)- and (S)-enantioselective enzyme cascades for deamination-decarboxylation-epoxidation-hydrolysis-oxidation-transamination were developed. The engineered E. coli strains produced (R)-1 a and (S)-1 a in high ee at 576 mg/L and 356 mg/L, respectively, from L-phenylalanine 6, as the first synthesis of these compounds from a bio-based chemical. Finally, L-phenylalanine biosynthesis pathway was combined with (R)- or (S)-enantioselective cascade in one strain or coupled strains, to achieve the first synthesis of (R)-1 a and (S)-1 a from a renewable feedstock. The coupled strain approach enhanced the production, affording 274 and 384 mg/L (R)-1 a and 274 and 301 mg/L (S)-1 a, from glucose and glycerol, respectively. The developed methods could be potentially useful to produce these high-value chemicals from cheap starting materials and renewable feedstocks in a green and sustainable manner. (Figure presented.).