56613-80-0Relevant articles and documents
Reactive extraction of enantiomers of 1,2-amino alcohols via stereoselective thermodynamic and kinetic processes
Tang, Lijun,Choi, Sujung,Nandhakumar, Raju,Park, Flyunjung,Chung, Hyein,Chin, Jik,Kwan, Mook Kim
, p. 5996 - 5999 (2008)
(Chemical Equation Presented) (R)-Amino alcohol with an enantiomeric excess of >95% was resolved by reactive extraction processes from 2 equiv of racemic alcohol using a chiral receptor 2 as an enantioselective extractant. One resolution cycle is composed of three extractions: a stereoselective reversible imine formation, a stereoselective irreversible imine hydrolysis, and the recovery of 2 and enantiomeric amino alcohols.
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.
Highly Stable Zr(IV)-Based Metal-Organic Frameworks for Chiral Separation in Reversed-Phase Liquid Chromatography
Jiang, Hong,Yang, Kuiwei,Zhao, Xiangxiang,Zhang, Wenqiang,Liu, Yan,Jiang, Jianwen,Cui, Yong
supporting information, p. 390 - 398 (2021/01/13)
Separation of racemic mixtures is of great importance and interest in chemistry and pharmacology. Porous materials including metal-organic frameworks (MOFs) have been widely explored as chiral stationary phases (CSPs) in chiral resolution. However, it remains a challenge to develop new CSPs for reversed-phase high-performance liquid chromatography (RP-HPLC), which is the most popular chromatographic mode and accounts for over 90% of all separations. Here we demonstrated for the first time that highly stable Zr-based MOFs can be efficient CSPs for RP-HPLC. By elaborately designing and synthesizing three tetracarboxylate ligands of enantiopure 1,1′-biphenyl-20-crown-6, we prepared three chiral porous Zr(IV)-MOFs with the framework formula [Zr6O4(OH)8(H2O)4(L)2]. They share the same flu topological structure but channels of different sizes and display excellent tolerance to water, acid, and base. Chiral crown ether moieties are periodically aligned within the framework channels, allowing for stereoselective recognition of guest molecules via supramolecular interactions. Under acidic aqueous eluent conditions, the Zr-MOF-packed HPLC columns provide high resolution, selectivity, and durability for the separation of a variety of model racemates, including unprotected and protected amino acids and N-containing drugs, which are comparable to or even superior to several commercial chiral columns for HPLC separation. DFT calculations suggest that the Zr-MOF provides a confined microenvironment for chiral crown ethers that dictates the separation selectivity.
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.).
Site-Specific C(sp3)–H Aminations of Imidates and Amidines Enabled by Covalently Tethered Distonic Radical Anions
Fang, Yuanding,Fu, Kang,Shi, Lei,Zhao, Rong,Zhou, Jia
supporting information, p. 20682 - 20690 (2020/09/07)
The utilization of N-centered radicals to synthesize nitrogen-containing compounds has attracted considerable attention recently, due to their powerful reactivities and the concomitant construction of C?N bonds. However, the generation and control of N-centered radicals remain particularly challenging. We report a tethering strategy using SOMO-HOMO-converted distonic radical anions for the site-specific aminations of imidates and amidines with aid of the non-covalent interaction. This reaction features a remarkably broad substrate scope and also enables the late-stage functionalization of bioactive molecules. Furthermore, the reaction mechanism is thoroughly investigated through kinetic studies, Raman spectroscopy, electron paramagnetic resonance spectroscopy, and density functional theory calculations, revealing that the aminations likely involve direct homolytic cleavage of N?H bonds and subsequently controllable 1,5 or 1,6 hydrogen atom transfer.
Method for preparing amino alcohol compound by using halogenated intermediate
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, (2020/08/22)
The invention discloses a method for preparing an amino alcohol compound by utilizing a halogenated intermediate. According to the method, an oxygen-halogen bond can be prepared by utilizing cyclic diacyl peroxide and halogenated salt under an illumination condition, and the oxygen-halogen bond is prone to homolysis under an illumination condition to form an active free radical, so the amino alcohol is finally prepared. The novel method for synthesizing the amino alcohol is high in atom utilization rate, simple in synthesis method and high in yield, so the consumption of halide for reactions with synthesis values is reduced, and the purposes of environmental protection and green chemistry are better achieved.
Enantioselective radical C–H amination for the synthesis of β-amino alcohols
Nakafuku, Kohki M.,Zhang, Zuxiao,Wappes, Ethan A.,Stateman, Leah M.,Chen, Andrew D.,Nagib, David A.
, p. 697 - 704 (2020/07/02)
Asymmetric, radical C–H functionalizations are rare but powerful tools for solving modern synthetic challenges. Specifically, the enantio- and regioselective C–H amination of alcohols to access medicinally valuable chiral β-amino alcohols remains elusive. To solve this challenge, a radical relay chaperone strategy was designed, wherein an alcohol was transiently converted to an imidate radical that underwent intramolecular H-atom transfer (HAT). This regioselective HAT was also rendered enantioselective by harnessing energy transfer catalysis to mediate selective radical generation and interception by a chiral copper catalyst. The successful development of this multi-catalytic, asymmetric, radical C–H amination enabled broad access to chiral β-amino alcohols from a variety of alcohols containing alkyl, allyl, benzyl and propargyl C–H bonds. Mechanistic experiments revealed that triplet energy sensitization of a Cu-bound radical precursor facilitates catalyst-mediated HAT stereoselectivity, enabling the synthesis of several important classes of chiral β-amines by enantioselective, radical C–H amination. [Figure not available: see fulltext.]
General Method for the Asymmetric Synthesis of N-H Sulfoximines via C-S Bond Formation
Argent, Stephen P.,Lewis, William,Mendon?a Matos, Priscilla,Moore, Jonathan c.,Stockman, Robert A.
supporting information, (2020/03/30)
A versatile method for the synthesis of enantioenriched N-H sulfoximines is reported. The approach stems from the organomagnesium-mediated ring opening of novel cyclic sulfonimidate templates. The reactions proceed in high yield and with excellent stereofidelity with alkyl, aryl, and heteroaryl Grignard reagents. The chiral auxiliary is readily removed from the resultant sulfoximines via an unusual oxidative debenzylation protocol that utilizes molecular oxygen as the terminal oxidant. This provides a general strategy for the synthesis of highly enantioenriched N-H sulfoximines.
Monofluoroalkene-Isostere as a 19F NMR Label for the Peptide Backbone: Synthesis and Evaluation in Membrane-Bound PGLa and (KIGAKI)3
Drouin, Myriam,Wadhwani, Parvesh,Grage, Stephan L.,Bürck, Jochen,Reichert, Johannes,Tremblay, Sébastien,Mayer, Marie Sabine,Diel, Christian,Staub, Alexander,Paquin, Jean-Fran?ois,Ulrich, Anne S.
supporting information, p. 1511 - 1517 (2020/02/05)
Solid-state 19F NMR is a powerful method to study the interactions of biologically active peptides with membranes. So far, in labelled peptides, the 19F-reporter group has always been installed on the side chain of an amino acid. Given the fact that monofluoroalkenes are non-hydrolyzable peptide bond mimics, we have synthesized a monofluoroalkene-based dipeptide isostere, Val-Ψ[(Z)-CF=CH]-Gly, and inserted it in the sequence of two well-studied antimicrobial peptides: PGLa and (KIGAKI)3 are representatives of an α-helix and a β-sheet. The conformations and biological activities of these labeled peptides were studied to assess the suitability of monofluoroalkenes for 19F NMR structure analysis.
Aryl olefin azole derivative as well as preparation method and application thereof
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Paragraph 0065; 0068-0069, (2021/01/15)
The invention belongs to the technical field of medicines, and relates to an aryl olefin azole derivative shown in a general formula I, stereoisomers thereof and pharmaceutically acceptable salts, hydrates, solvates or prodrugs thereof, and substituent groups Ar, R and X have definitions given in the specification. The invention also relates to a method for preparing the compound as shown in the general formula I, a medicinal composition containing the compound and application of the compound and the medicinal composition in preparation of medicines for treating and preventing superficial fungal and deep fungal diseases.
