- Characterization of a newly synthesized epoxide hydrolase and its application in racemic resolution of (R,S)-epichlorohydrin
-
In the current study, an epoxide hydrolase (EH) gene from Rhodosporidium toruloides was synthesized and expressed in Escherichia coli. After purification, we found that the optimal pH and temperature of this enzyme were 7.5 and 35°C, respectively. The recombinant EH obtained in this study was temperature-sensitive and the activity decreased significantly above 45°C. The values of apparent Km and Vmax were 0.5953 mol/l and 0.0105 mol/(L?min). In addition, enantiomeric excesses value of (R)-epichlorohydrin could reach 100% after 40-min reaction. Moreover, this EH showed a broad substrates specificity toward epoxides. To the best of our knowledge, this is the first time to report the application of R. toruloides EH in racemic resolution of (R,S)-epichlorohydrin to produce (R)-epichlorohydrin.
- Liu, Zhi-Qiang,Zhang, Li-Ping,Cheng, Feng,Ruan, Li-Tao,Hu, Zhong-Ce,Zheng, Yu-Guo,Shen, Yin-Chu
-
-
Read Online
- The Chiral Target of Daptomycin Is the 2R,2′S Stereoisomer of Phosphatidylglycerol
-
Daptomycin (dap) is an important antibiotic that interacts with the bacterial membrane lipid phosphatidylglycerol (PG) in a calcium-dependent manner. The enantiomer of dap (ent-dap) was synthesized and was found to be 85-fold less active than dap against
- Moreira, Ryan,Taylor, Scott D.
-
-
- Investigating the Individual Importance of the Pam2Cys Ester Motifs on TLR2 Activity
-
TLR2 agonists are at the forefront of vaccine research for a plethora of diseases, in particular they offer a promising tool for the treatment of cancer. A detailed knowledge of their structure–activity relationship informs the methodical design of vaccin
- Brimble, Margaret A.,Dunbar, P. Rod,Kelch, Inken D.,Li, Freda F.,Lu, Benjamin L.,Williams, Geoffrey M.
-
supporting information
p. 5415 - 5423
(2021/10/25)
-
- Dendritic Oligoglycerol Regioisomer Mixtures and Their Utility for Membrane Protein Research
-
Dendrons are an important class of macromolecules that can be used for a broad range of applications. Recent studies have indicated that mixtures of oligoglycerol detergent (OGD) regioisomers are superior to individual regioisomers for protein extraction. The origin of this phenomenon remains puzzling. Here we discuss the synthesis and characterization of dendritic oligoglycerol regioisomer mixtures and their implementation into detergents. We provide experimental benchmarks to support quality control after synthesis and investigate the unusual utility of OGD regioisomer mixtures for extracting large protein quantities from biological membranes. We anticipate that our findings will enable the development of mixed detergent platforms in the future.
- Urner, Leonhard H.,Goltsche, Katharina,Selent, Marleen,Liko, Idlir,Schweder, Marc-Philip,Robinson, Carol V.,Pagel, Kevin,Haag, Rainer
-
supporting information
p. 2537 - 2542
(2020/12/30)
-
- Synthesis and catalytic evaluation of acidic carbons in the etherification of glycerol obtained from biodiesel production
-
In this paper, the catalytic behaviour of carbonaceous system (Ccs) functionalized with –SO3H groups were studied in the etherification of refined (Gly) and crude glycerol (GlyC), with benzyl alcohol (BA). This Ccs was obtained by a synthetic method with low energetic cost in only 24 h. Its catalytic activity and selectivity were studied varying the catalyst percentage (2.5, 5 and 10 wt.%), the initial reactant molar ratio and temperature (between 80 and 120 °C). A very good catalytic performance was achieved (97 % conversion after 360 min of reaction), at 120 °C, Gly:BA = 3:1 and 10 wt.% of Ccs. The high activity can be attributed to high acid site density (6.4 mmol H+/g), that also allowed us to working at lower reaction temperature (100 °C) and with less catalyst concentration (2.5 wt.%), without observing significant loss in BA conversion. Monoether (ME1) was the major product of the reaction with 72 % selectivity. The material can be reused and still gives a notable conversion of BA (about 43 %) after three successive reuses. Finally, the Ccs was active and selective to the desired products in the etherification of crude glycerol (GlyC) derived of biodiesel industry. An important BA conversion (45 %) was obtained only reducing the water content of GlyC and without carrying out any other purification and/or neutralization treatment.
- Chiosso, María E.,Casella, Mónica L.,Merlo, Andrea B.
-
p. 107 - 114
(2020/10/29)
-
- Preparation, supramolecular aggregation and immunological activity of the bona fide vaccine adjuvant sulfavant S
-
In aqueous conditions, amphiphilic bioactive molecules are able to form self-assembled colloidal structures modifying their biological activity. This behavior is generally neglected in preclinical studies, despite its impact on pharmacological development. In this regard, a significative example is represented by a new class of amphiphilic marine-inspired vaccine adjuvants, collectively named Sulfavants, based on the β-sulfoquinovosyl-diacylglyceride skeleton. The family includes the lead product Sulfavant A (1) and two epimers, Sulfavant R (2) and Sulfavant S (3), differing only for the stereochemistry at C-2 of glycerol. The three compounds showed a significant difference in immunological potency, presumably correlated with change of the aggregates in water. Here, a new synthesis of diastereopure 3 was achieved, and the study of the immunomodulatory behavior of mixtures of 2/3 proved that the bizarre in vitro response to 1–3 effectively depends on the supramolecular aggregation states, likely affecting the bioavailability of agonists that can effectively interact with the cellular targets. The evidence obtained with the mixture of pure Sulfavant R (2) and Sulfavant S (3) proves, for the first time, that supramolecular organization of a mixture of active epimers in aqueous solution can bias evaluation of their biological and pharmacological potential.
- Manzo, Emiliano,Fioretto, Laura,Gallo, Carmela,Ziaco, Marcello,Nuzzo, Genoveffa,D’Ippolito, Giuliana,Borzacchiello, Assunta,Fabozzi, Antonio,de Palma, Raffaele,Fontana, Angelo
-
-
- MACROCYCLIC CHELATORS AND METHODS OF USE THEREOF
-
Macrocyclic chelators (I) for chelation of alpha-emitting radiometal ions, such as actinium-225 are provided. Also provided are radiometal complexes containing an alpha-emitting radiometal ion bound to the macrocyclic chelator via coordinate bonding, and radioimmunoconjugates containing the radiometal complexes covalently linked to a targeting ligand, such as an antibody or antigen binding fragment thereof. The radioimmunoconjugates can be produced by click chemistry reactions. Methods of using the radiocomplexes and radioimmunoconjugates for selectively targeting neoplastic cells for radiotherapy and for treating neoplastic diseases and disorders are also described.
- -
-
Page/Page column 99; 102; 103; 139-141
(2020/11/30)
-
- Synthesis of enantiopure ABC-type triacylglycerols
-
The synthesis of twelve enantiopure structured triacylglycerols (TAGs) of the ABC type possessing three different fatty acids is described by a six-step chemoenzymatic approach starting from (S)-solketal. Eight of the TAGs possess two different saturated fatty acyl groups located in the sn-1 and sn-2 positions with an unsaturated fatty acyl group in the remaining sn-3 position of the glycerol skeleton, whereas the remaining four possess two different saturated acyl groups in the terminal sn-1 and sn-3 positions with an unsaturated acyl group in the sn-2 position. The former group was synthesised by a six-step chemoenzymatic route involving a highly regioselective immobilised Candida antarctica lipase. The second group was prepared by a similar six-step approach, that required two separate lipase steps. Such enantiopure TAGs are strongly demanded as standards for enantiospecific analysis of intact TAGs in fats and oils.
- Gudmundsson, Haraldur G.,Linderborg, Kaisa M.,Kallio, Heikki,Yang, Baoru,Haraldsson, Gudmundur G.
-
-
- COMPOUNDS, DERIVATIVES, AND ANALOGS FOR CANCER
-
The instant invention provides for inositol derivatives, analogs, methods of preparation and uses that inhibit oncogenic signaling pathways and genes. In particular, the compounds disclosed selectively inhibit one or two classes and or isoforms of PI3K. T
- -
-
Paragraph 0031; 0188
(2020/02/16)
-
- H-Phosphonate Synthesis and Biological Evaluation of an Immunomodulatory Phosphoglycolipid from Thermophilic Bacteria
-
The synthesis of a library of bacterial phosphoglycolipid, PGL-1, is described. Key features of the synthesis include regioselective esterification of the primary alcohol of the diacylglycerol moiety and an H-phosphonate method to install the phosphate in PGL-1 in comparison with earlier reported procedures. A representative set of PGL-1 analogues was prepared and evaluated for their biological activities. Results showed that the immunological activity of PGL-1 is dependent on the chain lengths of the fatty acids.
- Gan, Chin Heng,Hua, Kuo-Feng,Lam, Yulin,Li, Lan-Hui,Peng, Yi-Jen,Wei, Chih-Feng,Wijaya, Hadhi,Wu, Shih-Hsiung
-
supporting information
(2020/04/02)
-
- Synthesis and enantiospecific analysis of enantiostructured triacylglycerols containing n-3 polyunsaturated fatty acids
-
The stereospecific structure of triacylglycerols (TAGs) affects the bioavailability of fatty acids. Lack of enantiopure reference compounds and effective enantiospecific methods have hindered the stereospecific analysis of individual TAGs. Twelve novel enantiostructured AAB-type TAGs were synthesized containing one of the three n-3 polyunsaturated fatty acid: α-linolenic acid (ALA), eicosapentaenoic acid (EPA), or docosahexaenoic acid (DHA) in sn-1 or sn-3 position. These compounds formed six enantiomer pairs, which were separated with recycling high-performance liquid chromatography using chiral columns and UV detection. The chromatographic retention behavior of the enantiomers and the stereospecific elution order were studied. The enantiomer with an n-3 PUFA in the sn-1 position eluted faster than the enantiomer with the n-3 PUFA in the sn-3 position, regardless of the carbon chain length and number of double bonds of the PUFA. TAG enantiomers containing DHA exhibited highly different retention on the chiral column and were separated after the first column, whereas recycling was needed to separate the enantiomer pairs containing ALA or EPA. The system using two identical columns and one mobile phase, without sample derivatization, proved to be very effective also for peak purity assessment, confirming the enantiopurity of the synthesized structured TAGs being higher than 98 percent (96 percent ee).
- Gudmundsson, Haraldur G.,Haraldsson, Gudmundur G.,Kallio, Heikki,Kalpio, Marika,Linderborg, Kaisa M.,Magnússon, Jóhann D.,Yang, Baoru
-
-
- Highly regio- and enantio-selective hydrolysis of two racemic epoxides by GmEH3, a novel epoxide hydrolase from Glycine max
-
A novel epoxide hydrolase from Glycine max, designated GmEH3, was excavated based on the computer-aided analysis. Then, gmeh3, a GmEH3-encoding gene, was cloned and successfully expressed in E. coli Rosetta(DE3). Among the ten investigated rac-epoxides, GmEH3 possessed the highest and best complementary regioselectivities (regioselectivity coefficients, αS = 93.7% and βR = 97.2%) in the asymmetric hydrolysis of rac-m-chlorostyrene oxide (5a), and the highest enantioselectivity (enantiomeric ratio, E = 55.6) towards rac-phenyl glycidyl ether (7a). The catalytic efficiency (kcatS/KmS = 2.50 mM?1 s?1) of purified GmEH3 for (S)-5a was slightly higher than that (kcatR/KmR = 1.52 mM?1 s?1) for (R)-5a, whereas the kcat/Km (5.16 mM?1 s?1) for (S)-7a was much higher than that (0.09 mM?1 s?1) for (R)-7a. Using 200 mg/mL wet cells of E. coli/gmeh3 as the biocatalyst, the scale-up enantioconvergent hydrolysis of 150 mM rac-5a at 25 °C for 1.5 h afforded (R)-5b with 90.2% eep and 95.4% yieldp, while the kinetic resolution of 500 mM rac-7a for 2.5 h retained (R)-7a with over 99% ees and 43.2% yields. Furthermore, the sources of high regiocomplementarity of GmEH3 for (S)- and (R)-5a as well as high enantioselectivity towards rac-7a were analyzed via molecular docking (MD) simulation.
- Zhang, Chen,Li, Chuang,Zhu, Xiu-xiu,Liu, You-yi,Zhao, Jun,Wu, Min-chen
-
p. 2795 - 2803
(2020/09/01)
-
- Selective monochlorination of unsymmetrical vicinal diols with chlorinated iminium chlorides
-
Chlorinated iminium chlorides have been identified to promote the highly efficient and selective mono-chlorination of unsymmetrical vicinal diols. Vilsmeier reagent, namely, (chloromethylene)dimethyliminium chloride, enables highly reactive and regioselective chlorination of 1,2- and 1,3-diols featured one secondary benzylic hydroxy group and one primary aliphatic hydroxy group to give the corresponding 1,2- and 1,3-chlorohydrins. Viehe's salts (α,α-dichloro iminium salts) exhibit excellent reactivity and good selectivity for vicinal diols to give the corresponding chlorohydrin carbamates via a cyclic intermediate in situ. The chlorination protocols tolerate diverse functional groups, including halogens, naphthalene rings, nitro, and cyano. Moreover, the optical purity of chiral diols could be retained during this chlorination reaction.
- Li, Chengyang,Li, Xiaotong,Wang, Yu,Wu, Xiaoyu,Xie, Xiaomin,Yang, Liqun,Zhang, Zhaoguo
-
supporting information
(2020/03/23)
-
- POLY(PHOSPHOESTERS) FOR DELIVERY OF NUCLEIC ACIDS
-
Disclosed are polymers comprising the moiety A, which is a moiety of formula I: and pharmaceutically acceptable salts thereof, wherein R, R1, R2, L, n1 and n2 are as defined herein. These polymers are useful for delivering nucleic acids to subject. These polymers and pharmaceutically acceptable compositions comprising such polymers and nucleic acids can be useful for treating various diseases, disorders and conditions.
- -
-
-
- COMPOSITIONS AND METHODS FOR THE TREATMENT OF PARKINSON'S DISEASE
-
The invention relates to the compounds of formula I, formula II and/or formula III or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compound of formula I, formula II or formula III, and methods for treating or preventing Parkinson's disease may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, subcutaneous, depot, intramuscular, syrup, or injection. Such compositions may be used to treatment or management of Parkinson's disease as well as scleroderma, restless leg syndrome, hypertension and gestational hypertension.
- -
-
Page/Page column 46
(2020/05/19)
-
- Glycerol conversion to high-value chemicals: The implication of unnatural α-amino acid syntheses using natural resources
-
Glycerol derivatives are an important class of compounds, which have great applications as basic structural building blocks in organic synthesis. O-Benzylglycerol was oxidised to produce a high-value compound in high yield using a NaOtBu-O2 system. Furthermore, the synthetic utility of the resulting product was demonstrated by its transformation into unnatural α-amino acids, thus showing the valorisation of glycerol biomass.
- Park, Yun Ji,Yang, Jung Woon
-
supporting information
p. 2615 - 2620
(2019/06/03)
-
- Site-Selective Mono-Oxidation of 1,2-Bis(boronates)
-
Site-selective oxidation of vicinal bis(boronates) is accomplished through the use of trimethylamine N-oxide in 1-butanol solvent. The reaction occurs with good efficiency and selectivity across a range of substrates, providing 2-hydro-1-boronic esters which are shown to be versatile intermediates in the synthesis of chiral building blocks.
- Yan, Lu,Morken, James P.
-
supporting information
p. 3760 - 3763
(2019/05/24)
-
- HYDROPHOBIC ACID ADDITION SALTS AND PHARMACEUTICAL FORMULATIONS THEREOF
-
The invention provides hydrohphobic drug salts and pharmaceutical compositions comprising such salts. The invention fourther provides compositions for delivering poorly soluble drugs, including hydrophobic drug salts.
- -
-
Page/Page column 81
(2019/05/22)
-
- Preparation of benzothiazolyl-decorated nanoliposomes
-
Amyloid β (Aβ) species are considered as potential targets for the development of diagnostics/therapeutics towards Alzheimer’s disease (AD). Nanoliposomes which are decorated with molecules having high affinity for Aβ species may be considered as potential carriers for AD theragnostics. Herein, benzothiazolyl (BTH) decorated nanoliposomes were prepared for the first time, after synthesis of a lipidic BTH derivative (lipid-BTH). The synthetic pathway included acylation of bis(2-aminophenyl) disulfide with palmitic acid or palmitoyl chloride and subsequent reduction of the oxidized dithiol derivative. The liberated thiols were able to cyclize to the corresponding benzothiazolyl derivatives only after acidification of the reaction mixture. Each step of the procedure was monitored by HPLC analysis in order to identify all the important parameters for the formation of the BTH-group. Finally, the optimal methodology was identified, and was applied for the synthesis of the lipid-BTH derivative. BTH-decorated nanoliposomes were then prepared and characterized for physicochemical properties (size distribution, surface charge, physical stability, and membrane integrity during incubation in presence of buffer and plasma proteins). Pegylated BTH-nanoliposomes were demonstrated to have high integrity in the presence of proteins (in comparison to non-peglated ones) justifying their further exploitation as potential theragnostic systems for AD.
- Mourtas, Spyridon,Christodoulou, Panayiota,Klepetsanis, Pavlos,Gatos, Dimitrios,Barlos, Kleomenis,Antimisiaris, Sophia G.
-
-
- Regioselective Ring-Opening of Glycidol to Monoalkyl Glyceryl Ethers Promoted by an [OSSO]-FeIII Triflate Complex
-
A FeIII-triflate complex, bearing a bis-thioether-di-phenolate [OSSO]-type ligand, was discovered to promote the ring-opening of glycidol with alcohols under mild reaction conditions (0.05 mol % catalyst and 80 °C). The reaction proceeded with high activity (initial turnover frequency of 1680 h?1 for EtOH) and selectivity (>95 %) toward the formation of twelve monoalkyl glyceryl ethers (MAGEs) in a regioselective fashion (84–96 % yield of the non-symmetric regioisomer). This synthetic approach allows the conversion of a glycerol-derived platform molecule (i.e., glycidol) to high-value-added products by using an Earth-crust abundant metal-based catalyst.
- Monica, Francesco Della,Ricciardi, Maria,Proto, Antonio,Cucciniello, Raffaele,Capacchione, Carmine
-
p. 3448 - 3452
(2019/08/01)
-
- Synthetic method of alkynyl-modified phospholipid derivative for preparing functional phospholipid giant vesicle
-
The invention discloses a synthetic method of an alkynyl-modified phospholipid derivative for preparing a functional phospholipid giant vesicle. The method comprises the following steps: with solketalas a starting raw material, selectively introducing an alkyl chain through benzyl protection, deprotection and DCC-DMAP catalytic condensation, synthesizing 3-hydroxy-1,2- dipalmitin, using 2-chloro-2-oxo-1,3,2-dioxaphospholane as a phosphorylation reagent, carrying out ring opening reaction by using 1-dimethylamine-2-allylene, and preparing the alkynyl-modified phospholipid derivative. The method is simple in synthetic route, a highly toxic reagent does not need to be used, and the phospholipid giant vesicle with an adjustable surface reactivity group density can be prepared by mixing the obtained alkynyl-modified phospholipid derivative and common phospholipid available in the market according to a certain proportion. The possibility is provided for the further stabilization and functionalization of this type of the vesicle.
- -
-
-
- Synthesis process of novel compound phosphatidyl 3-hydroxypropionitrile
-
The invention relates to a synthesis process of a novel compound phosphatidyl 3-hydroxypropionitrile. The synthesis process comprises the following steps: using acetone glycerol as a starting material; protecting exposed hydroxyl with benzyl; removing a ketal protecting group to obtain two exposed hydroxyls; then, esterifying with stearic acid; removing benzyl protection to obtain the exposed hydroxyl; reacting with a chlorophosphine compound to obtain a phosphine oxide compound; oxidizing to obtain phosphine oxide; and removing one molecular propyl nitrile to obtain a final product phosphatidyl 3-hydroxypropionitrile.
- -
-
Paragraph 0010
(2018/09/21)
-
- Raw and waste plant materials as sources of fungi with epoxide hydrolase activity. Application to the kinetic resolution of aryl and alkyl glycidyl ethers
-
The by-products of olive oil production can be used as sources of microbial strains. Penicillium sp., Aspergillus terreus, Penicillium aurantiogriseum, Aspergillus tubingensis and Aspergillus niger were selected on the basis of their epoxide-hydrolyzing activity towards racemic rac-glycidyl phenyl ether. We studied the effect on enzymatic activity of adding styrene oxide to the growth medium. It induced the biosynthesis of epoxide hydrolases and reduced cell growth. The resolution capacity of the five fungi was tested on rac-glycidyl phenyl ether, rac-benzyl glycidyl ether, rac-1,2-epoxyhexane and rac-1,2-epoxyoctane. The resolution of rac-glycidyl phenyl ether by A. niger, rac-benzyl glycidyl ether by P. aurantiogriseum and A. terreus, rac-1,2-epoxyhexane by A. tubingensis and rac-1,2-epoxyoctane by A. terreus provided (S)-3-phenoxy-1,2-propanediol (45.1% yield, 51.4% ee), (R)-3-benzyloxy-1,2-propanediol (40.8% yield, 43.3% ee), (S)-3-benzyloxy-1,2-propanediol (45.4% yield, 45.6% ee), (R)-1,2-hexanediol (70.4% yield, 24.4% ee) and (R)-1,2-octanediol (21.4% yield, 27.5% ee), respectively. The (R)-enantiopreference of the epoxide hydrolases from P. aurantiogriseum is unprecedented.
- Dolcet, Marta,Torres, Mercè,Canela-Garayoa, Ramon
-
-
- Hydrogenation of CO2-Derived Carbonates and Polycarbonates to Methanol and Diols by Metal–Ligand Cooperative Manganese Catalysis
-
The first base-metal-catalysed hydrogenation of CO2-derived carbonates to alcohols is presented. The reaction proceeds under mild conditions in the presence of a well-defined manganese complex with a loading as low as 0.25 mol %. The non-precious-metal homogenous catalytic system provides an indirect route for the conversion of CO2 into methanol with the co-production of value-added (vicinal) diols in yields of up to 99 %. Experimental and computational studies indicate a metal–ligand cooperative catalysis mechanism.
- Zubar, Viktoriia,Lebedev, Yury,Azofra, Luis Miguel,Cavallo, Luigi,El-Sepelgy, Osama,Rueping, Magnus
-
supporting information
p. 13439 - 13443
(2018/09/21)
-
- Stereodivergent approach to Alzheimer's therapeutic agent (R)-(?) and (S)-(+)-arundic acid employing chiral 4-pentenol derivatives as building blocks
-
An efficient stereodivergent total synthesis of anti-Alzheimer agent (R)-(?) and (S)-(+)-arundic acid has been achieved from both chiral and nonchiral materials. This strategy features an efficient approach to separable diastereomeric C-2 chiral 4-pentenol intermediates employing proline catalysed asymmetric α-aminooxylation and [3,3] sigmatropic Claisen rearrangement are the highlights of present synthesis.
- Bhosale, Viraj A.,Waghmode, Suresh B.
-
p. 2342 - 2348
(2017/04/03)
-
- Asymmetric Hydrolytic and Aminolytic Kinetic Resolution of Racemic Epoxides using Recyclable Macrocyclic Chiral Cobalt(III) Salen Complexes
-
New chiral macrocyclic cobalt(III) salen complexes were synthesized and used as catalyst for the asymmetric kinetic resolution (AKR) of terminal epoxides and glycidyl ethers with aromatic/aliphatic amines and water as nucleophiles. This is the first occasion where a Co(III) salen complex demonstrated its ability to catalyze AKR as well as hydrolytic kinetic resolution (HKR) reactions. Excellent enantiomeric excesses of the epoxides, the corresponding amino alcohols and diols (upto 99%) with quantitative yields were achieved by using the chiral Co(III) salen complexes in dichloromethane at room temperature. This protocol was further extended for the synthesis of two important drug molecules, i.e., (S)-propranolol and (R)-naftopidil. The catalytic system was also explored for the synthesis of chirally pure diols and chiral cyclic carbonates using carbon dioxide as a greener renewable C1 source. The catalyst was recycled for upto 5 catalytic cycles with retention of enantioselectivity. (Figure presented.).
- Tak, Rajkumar,Kumar, Manish,Menapara, Tusharkumar,Gupta, Naveen,Kureshy, Rukhsana I.,Khan, Noor-ul H.,Suresh
-
supporting information
p. 3990 - 4001
(2017/11/22)
-
- Copper-catalyzed/mediated borylation reactions of epoxides with diboron reagents: access to β-hydroxyl boronic esters
-
We report the first copper-catalyzed/mediated borylative ring opening reaction of epoxides. This process represents a direct borylative C(sp3)-O bond cleavage of terminal epoxide substrates with commercially available diboron reagents. A wide range of epoxides with different functional groups are involved, and were subsequently converted to the corresponding β-hydroxyl boronic esters smoothly. Moreover, the ring opening product β-pinacol boronate alcohol provided a more beneficial approach for the formation of C-C and C-N bonds.
- Ahmed, Ebrahim-Alkhalil M. A.,Lu, Xi,Gong, Tian-Jun,Zhang, Zhen-Qi,Xiao, Bin,Fu, Yao
-
p. 909 - 912
(2017/01/17)
-
- Efficient diastereoselective synthesis of a new class of azanucleosides: 2′-homoazanucleosides
-
Azanucleosides, sugar-modified nucleoside analogues containing a 4′ nitrogen atom, have shown a lot of therapeutic potential, e.g. as anti-cancer and antiviral agents. We report the synthesis of a series of 2’-homoazanucleosides, in which the nucleobase is attached to the 2’-position of the pyrrolidine ring via a methylene linker. A suitable orthogonally protected iminosugar was synthesized by ring closing metathesis and dihydroxylation as key steps and further converted to a series of 8 nucleoside analogues through Mitsunobu reaction with suitably protected nucleobases. The 5′ position of the adenine analogue was then further derivatized with thiols to afford 2 additional compounds. The final compounds were evaluated for biological activity.
- Bouton, Jakob,Van Hecke, Kristof,Van Calenbergh, Serge
-
p. 4307 - 4316
(2017/06/30)
-
- COMPOSITIONS AND METHODS FOR DELIVERY OF THERAPEUTIC AGENTS
-
This disclosure provides improved lipid-based compositions, including lipid nanoparticle compositions, and methods of use thereof for delivering agents in vivo including nucleic acids and proteins. These compositions are not subject to accelerated blood clearance and they have an improved toxicity profile in vivo.
- -
-
-
- Asymmetric hydrolysis of styrene oxide by PvEH2, a novel Phaseolus vulgaris epoxide hydrolase with extremely high enantioselectivity and regioselectivity
-
A novel EH from Phaseolus vulgaris, PvEH2, was discovered based on the computer-aided analysis, and its encoding gene was cloned and expressed in E. coli Rossetta (DE3). The substrate spectrum of recombinant (re) PvEH2 was assayed, among which the enantiomeric ratio of rePvEH2 towards racemic styrene oxide (rac-1a) was > 200, while its regioselectivity coefficients, αS and βR, towards (S)- and (R)-1a were 99.1 and 69.8%, respectively. The asymmetric hydrolysis of 20 mM rac-1a by rePvEH2-expressing whole cells was performed at 25 °C, retaining (R)-1a with > 99.5% ees and 49.4% yield and producing (R)-phenyl-1,2-ethanediol (1b) with 96.2% eep and 49.7% yield in 40 min.
- Li, Chuang,Hu, Die,Zong, Xun-Cheng,Deng, Chao,Feng, Lei,Wu, Min-Chen,Li, Jian-Fang
-
-
- Synthesis and immunological study of a wall teichoic acid-based vaccine against E. faecium U0317
-
A repeat unit of cell wall teichoic acids (WTA) isolated from E. faecium U0317 was chemically synthesized efficiently by a stepwise strategy. It was derivatized with a 5-aminopentanyl linker to facilitate conjugation with carrier proteins KLH and HSA. Immunological studies of the KLH conjugate 1 demonstrated that it could provoke robust immune responses and high titers of IgG antibodies, which could successfully recognize the synthesized WTA repeat unit 3. This result suggested that synthetic glycoconjugate 1 could be a promising vaccine candidate against E. faecium for further studies.
- Zhou, Zhifang,Ding, Wenzhang,Li, Chen,Wu, Zhimeng
-
p. 205 - 219
(2017/11/15)
-
- Remarkable functions of sn-3 hydroxy and phosphocholine groups in 1,2-diacyl-sn-glycerolipids to induce clockwise (+)-helicity around the 1,2-diacyl moiety: Evidence from conformation analysis by 1H NMR spectroscopy
-
Cell-membrane glycerolipids exhibit a common structural backbone of asymmetric 1,2-diacyl-sn-glycerol bearing polar head groups in the sn-3 position. In this study, the possible effects of sn-3 head groups on the helical conformational property around the 1,2-diacyl moiety in the solution state were examined. 1H NMR Karplus relation studies were carried out using a series of 1,2-dipalmitoyl-sn-glycerols bearing different sn-3 substituents (namely palmitoyl, benzyl, hydrogen, and phosphates). The 1H NMR analysis indicated that the helical property around the 1,2-diacyl moiety is considerably affected by these sn-3 substituents. The sn-3 hydroxy group induced a unique helical property, which was considerably dependent on the solvents used. In CDCl3 solution, three staggered conformers, namely gt(+), gg(?) and tg, were randomized, while in more polar solvents, the gt(+) conformer with (+)-helicity was amplified at the expense of gg(?) and tg conformers. The sn-3 phosphocholine in phosphatidylcholine exhibited a greater effect on the gt(+) conformer, which was independent of the solvents used. From the 1H NMR analysis, the helical conformational properties around the 1,2-diacyl moiety conformed to a simple empirical rule, which permitted the proposal of a conformational diagram for 1,2-dipalmitoyl-sn-glycerols in the solution states.
- Nishida, Yoshihiro,Yuan, Mengfei,Fukuda, Kazuo,Fujisawa, Kaito,Dohi, Hirofumi,Uzawa, Hirotaka
-
supporting information
p. 1999 - 2009
(2017/10/16)
-
- Synthesis, Characterization and Catalytic Application of Pyridine-Bridged N-Heterocyclic Carbene–Ruthenium Complexes in the Hydrogenation of Carbonates
-
A series of bulky pyridine-bridged NHC–Ru complexes have been rationally designed and synthesized; these exhibited very high catalytic activity in the hydrogenation of cyclic and linear carbonates under mild reaction conditions. In the presence of catalytic amounts of a weak base, a broad range of substrates with different ring size and steric bulk were well tolerated, providing methanol and the corresponding diols in excellent yields with a catalyst loading as low as 0.5 mol %.
- Chen, Jiangbo,Zhu, Haibo,Chen, Jinjin,Le, Zhang-Gao,Tu, Tao
-
supporting information
p. 2809 - 2812
(2017/10/23)
-
- Aerobic Acetoxyhydroxylation of Alkenes Co-catalyzed by Organic Nitrite and Palladium
-
An aerobic acetoxyhydroxylation of alkenes cooperatively catalyzed by organic nitrite and palladium at room temperature using clean and cheap air as the sole oxidant has been developed. Various vicinal diols, diacetoxyalkanes, and dihalogenoalkanes have been synthesized. The gram-scale synthesis has also been approached. Vicinal difluorination and dichlorolation products have also been achieved via this reaction.
- Chen, Xian-Min,Ning, Xiao-Shan,Kang, Yan-Biao
-
supporting information
p. 5368 - 5371
(2016/11/02)
-
- Percarboxylic Acid Oxidation of α-Hydroxy-Substituted Alkoxyallenes: The Unexpected Formation of Acyloxy-Substituted 1,2-Diketones and the Synthesis of Functionalized Quinoxalines
-
Treatment of α-hydroxy-substituted methoxyallene derivatives with meta-chloroperbenzoic acid provided acyloxy-substituted 1,2-diketones in moderate yields. A mechanism for the formation of these unexpected products is proposed. The configuration of the enantiopure compound (S)-1-(3-methylquinoxalin-2-yl)-1-(4-nitrobenzoyl?oxy)propan-2-yl 3-chlorobenzoate - determined by X-ray crystal structure analysis - indicates the intermediacy of a carbenium ion during formation of the 1,2-diketones. The functionalized 1,2-diketones are valuable starting materials for a variety of products as demonstrated by the synthesis of quinoxalines, an imidazole derivative, and electron-deficient alkenes.
- Klemme, Robby,Bentz, Christoph,Zukowski, Tomasz,Schefzig, Luise,Lentz, Dieter,Reissig, Hans-Ulrich,Zimmer, Reinhold
-
supporting information
p. 1491 - 1501
(2016/05/24)
-
- Chemo- and Regioselective Functionalization of Polyols through Catalytic C(sp3)-C(sp3) Kumada-Type Coupling of Cyclic Sulfate Esters
-
This contribution describes a copper-catalyzed, C(sp3)-C(sp3) cross-coupling reaction of cyclic sulfate esters, a distinct class of electrophilic derivatives of polyols, with alkyl Grignard reagents to afford functionalized alcohol products in good yields. The method is operationally simple and highlights the potential of cyclic sulfate esters as highly reactive substrates in catalytic, chemoselective polyol transformations.
- Ramírez-Contreras, Rodrigo,Morandi, Bill
-
supporting information
p. 3718 - 3721
(2016/08/16)
-
- A 1,2-O-double-hexadecyl-rac-glycerol synthesis method (by machine translation)
-
The invention discloses a 1,2-O-double-hexadecyl-rac-glycerol synthesis method, comprises first acetone mixed with the glycerine, to the toluene sulfonic acid as catalyst synthesis acetone compression glycerin, and then the acetone compression glycerin C1 hydroxy benzyl protection for 1-phenylmethyl -2,3-isopropylidene-rac-glycerin, then using a certain concentration of hydrochloric acid deprotected, to obtain 3-benzyloxy -1,2-propylene glycol, with the bromo-hexadecane william abdicates reaction occurred 1-O-benzyl -2,3-O-twenty-six alkyl glycerin, finally the hydrogen obtained remove benzyl under the action of a Pd 1,2-O-double-hexadecyl-rac-glycerin. The present invention provides a new synthetic 1,2-O-double-hexadecyl-rac-glycerin ways. (by machine translation)
- -
-
Paragraph 0065; 0066
(2016/10/17)
-
- Synthesis of Monoalkyl Glyceryl Ethers by Ring Opening of Glycidol with Alcohols in the Presence of Lewis Acids
-
The present work deals with the production of monoalkyl glyceryl ethers (MAGEs) through a new reaction pathway based on the reaction of glycidol and alcohols catalyzed by Lewis acid-based catalysts. Glycidol is quantitatively converted with high selectivity (99 %) into MAGEs under very mild reaction conditions (80 °C and 0.01 mol % catalyst loading) in only 1 h using Al(OTf)3 or Bi(OTf)3 as catalyst. The proposed method enhances the choice of possible green synthetic approaches for the production of value-added products such as MAGEs.
- Cucciniello, Raffaele,Ricciardi, Maria,Vitiello, Rosa,Di Serio, Martino,Proto, Antonio,Capacchione, Carmine
-
p. 3272 - 3275
(2016/12/16)
-
- PHOSPHOLIPID COMPOUND CONTAINING UNSATURATED FATTY ACID DERIVATIVE HAVING CYCLOPROPANE RING
-
The present invention aims to provide a medicine having a cognitive function improving effect and an anti-diabetes action. A phospholipid compound containing unsaturated fatty acid having a cyclopropane ring such as 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA) and 8-(2-octylcyclopropyl)octanoic acid (DCP-OA) and the like, particularly 1,2-o-bis-[8-{2-(2-pentyl-cyclopropylmethyl)-cyclopropyl}-octanoyl]-sn-glycero-3-phosphatidylethanolamine (diDCP-LA-PE), has a cognitive function improving effect and an anti-diabetes action, and is useful as a medicine such as a therapeutic drug for dementia, a therapeutic drug for diabetes and the like.
- -
-
Paragraph 0064
(2016/01/11)
-
- The role of mesoporosity and Si/Al ratio in the catalytic etherification of glycerol with benzyl alcohol using ZSM-5 zeolites
-
A comparative study of the influence of three different acid solids as catalysts (conventional zeolites Z15c with Si/Al = 19.5 and Z40c with Si/Al = 48.2, and a hierarchical zeolite Z40c-H with Si/Al = 50.0) for the etherification of glycerol with benzyl alcohol was performed. The catalytic activity and selectivity of these zeolites was elucidated at different catalyst contents. Three different ethers (3-benzyloxy-1,2-propanediol, which is a mono-benzyl-glycerol ether (MBG) and 1,3-dibenzyloxy-2-propanol, which is a di-benzyl-glycerol ether (DBG) and dibenzyl ether (DBz) were identified as the main products. MBG was the major product of the reaction catalyzed by the microporous Z15c zeolite with low Si/Al molar ratio, whereas DBG was formed in higher yield with the use of microporous Z40c and hierarchical Z40c-H zeolites, both of them having a similar high Si/Al molar ratio (≈50 MBG is a value-added product andit is obtained with good yield and selectivity when using the conventional zeolite Z15c as a catalyst.Under the best conditions tested, i.e., 25 mg of catalyst for 8 h at 120°C, a 62% of conversion was obtainedwithout the need of solvent, with an excellent 84% selectivity toward the MBG and no formation of DBz.
- Gonzalez-Arellano, Camino,Grau-Atienza, Aida,Serrano, Elena,Romero, Antonio A.,Garcia-Martinez, Javier,Luque, Rafael
-
-
- Synthesis of unsaturated phosphatidylinositol 4-phosphates and the effects of substrate unsaturation on SopB phosphatase activity
-
In this paper evidence is presented that the fatty acid component of an inositide substrate affects the kinetic parameters of the lipid phosphatase Salmonella Outer Protein B (SopB). A succinct route was used to prepare the naturally occurring enantiomer of phosphatidylinositol 4-phosphate (PI-4-P) with saturated, as well as singly, triply and quadruply unsaturated, fatty acid esters, in four stages: (1) The enantiomers of 2,3:5,6-O-dicyclohexylidene-myo-inositol were resolved by crystallisation of their di(acetylmandelate) diastereoisomers. (2) The resulting diol was phosphorylated regio-selectively exclusively on the 1-O using the new reagent tri(2-cyanoethyl)phosphite. (3) With the 4-OH still unprotected, the glyceride was coupled using phosphate tri-ester methodology. (4) A final phosphorylation of the 4-O, followed by global deprotection under basic then acidic conditions, provided PI-4-P bearing a range of sn-1-stearoyl, sn-2-stearoyl, -oleoyl, -γ-linolenoyl and arachidonoyl, glycerides. Enzymological studies showed that the introduction of cis-unsaturated bonds has a measurable influence on the activity (relative Vmax) of SopB. Mono-unsaturated PI-4-P exhibited a five-fold higher activity, with a two-fold higher KM, over the saturated substrate, when presented in DOPC vesicles. Poly-unsaturated PI-4-P showed little further change with respect to the singly unsaturated species. This result, coupled with our previous report that saturated PI-4-P has much higher stored curvature elastic stress than PI, supports the hypothesis that the activity of inositide phosphatase SopB has a physical role in vivo. This journal is
- Furse, Samuel,Mak, Lokhang,Tate, Edward W.,Templer, Richard H.,Ces, Oscar,Woscholski, Rüdiger,Gaffney, Piers R. J.
-
p. 2001 - 2011
(2015/03/05)
-
- Selective functionalization of the primary hydroxy group in triols
-
A procedure was suggested for preparing functionally substituted 1,2-diols by O-alkylation of hydroxyalkyl-1,3-dioxacyclanes with alkyl halides, followed by acid hydrolysis. The conditions for selective cleavage of the ethers obtained were found. (2,2-Dimethyl-1,3-dioxolan-4-yl)methyl benzoate under the conditions of acid deacetalization undergoes saponification of the ester group.
- Raskil'Dina,Valiev,Sultanova,Zlotskii
-
p. 1599 - 1604
(2016/02/18)
-
- Synthesis of Novel C-Pivot Lariat 18-Crown-6 Ethers and Their Efficient Purification
-
The syntheses of various lariat ethers including several not previously reported and their efficient purification are presented. The synthesis route brings together reactions from a variety of previous works leading to a robust and generalized approach to these C-pivot lariats. The main steps are condensation of functionalized diols with pentaethylene glycol ditosylate in the presence of potassium as a templating cation. Purification of the final products was achieved without chromatography by extracting from an aqueous potassium hydroxide solution.
- Jana, Susovan,Suresh, Vallabh,Lepore, Salvatore D.
-
p. 1977 - 1980
(2015/09/01)
-
- Supramolecular assemblies of novel aminonucleoside phospholipids and their bonding to nucleic acids
-
A novel class of aminonucleoside phospholipids has been developed. These molecules could spontaneously assemble into supramolecular structures including multilamellar organization, hydrogels, superhelical strands, and vesicles. Their ability to bind to DNA by hydrogen bonding and π-π stacking interactions was investigated by many means. This journal is
- Pan, Delin,Sun, Jing,Jin, Hongwei,Li, Yating,Li, Liyu,Wu, Yun,Zhang, Lihe,Yang, Zhenjun
-
supporting information
p. 469 - 472
(2015/02/19)
-
- Glycerol etherification with benzyl alcohol over sulfated zirconia catalysts
-
Glycerol (GLY) etherification with benzyl alcohol (BA) was conducted with different zirconia-based heterogeneous acid catalysts, aiming to produce mono- (ME) and dibenzyl glycerol ethers (DE). Physicochemical properties of the prepared catalysts were obtained through XRD, SEM and adsorption of ammonia. The catalytic tests were performed at different temperatures (120-140°C) and initial reactant mass ratios (GLY:BA 1:1 and 2:1). The highest BA conversions were obtained with the catalyst having the highest sulfuric acid content (2S/ZrO2). An increase in the reaction temperature and the GLY:BA initial mass ratio led to an increase in the BA conversion. Two kinetic models (a potential and a hyperbolic approach) were proposed to describe the process performance, including not only reactants evolution with time, but also that of ME, DE and the undesired self-condensation product of BA (benzyl ether, BE). Kinetic parameters for each model were estimated by data fitting and both models were able to accurately describe the evolution of the system, in terms of reactants and product distribution as a function of time under the experimental conditions studied.
- Jaworski, María A.,Rodríguez Vega, Sergio,Siri, Guillermo J.,Casella, Mónica L.,Romero Salvador, Arturo,Santos López, Aurora
-
-
- Synthesis of phosphoramidites of isoGNA, an isomer of glycerol nucleic acid
-
IsoGNA, an isomer of glycerol nucleic acid GNA, is a flexible (acyclic) nucleic acid with bases directly attached to its linear backbone. IsoGNA exhibits (limited) base-pairing properties which are unique compared to other known flexible nucleic acids. He
- Kim, Keunsoo,Punna, Venkateshwarlu,Karri, Phaneendrasai,Krishnamurthy, Ramanarayanan
-
p. 2131 - 2138
(2015/02/19)
-
- A new enantioselective synthesis of (S)-2-ethoxy-3-(4-hydroxyphenyl) propanoic acid esters (EEHP and IEHP), useful pharmaceutical intermediates of PPAR agonists
-
A new enantioselective synthetic route to the title compounds has been developed in a simple and practical way with high enantiopurity using commercially available starting material.
- Mujahid,Kunte,Muthukrishnan
-
supporting information
p. 3223 - 3226
(2014/06/09)
-
- Asymmetric hydrolytic kinetic resolution with recyclable polymeric Co(iii)-salen complexes: A practical strategy in the preparation of (S)-metoprolol, (S)-toliprolol and (S)-alprenolol: Computational rationale for enantioselectivity
-
A series of chiral polymeric Co(iii)-salen complexes based on a number of achiral and chiral linkers were synthesized and their catalytic performances were assessed in the asymmetric hydrolytic kinetic resolution of terminal epoxides. The effects of the linker were judiciously studied and it was found that in the case of the chiral BINOL-based polymeric salen complex 1, there was an enrichment in catalyst reactivity and enantioselectivity of the unreacted epoxide, particularly in the case of short as well as long chain aliphatic epoxides. Good isolated yields of the unreacted epoxide (up to 46% compared to 50% theoretical yield) along with high enantioselectivity (up to 99%) were obtained in most cases using catalyst 1. Further studies showed that catalyst 1 could retain its catalytic activity for six cycles under the present reaction conditions without any significant loss in activity or enantioselectivity. To show the practical applicability of the above synthesized catalyst we have synthesised some potent chiral β-blockers in moderate yield and high enantioselectivity using complex 1. The DFT (M06-L/6-31+G??//ONIOM(B3LYP/6-31G?:STO-3G)) calculations revealed that the chiral BINOL linker influences the enantioselectivity achieved with Co(iii)-salen complexes. Further, the transition state calculations show that the R-BINOL linker with the (S,S)-Co(iii)-salen complex is energetically preferred over the corresponding S-BINOL linker with the (S,S)-Co(iii)-salen complex for the HKR of 1,2-epoxyhexane. The role of non-covalent C-H?π interactions and steric effects has been discussed to control the HKR reaction of 1,2-epoxyhexane.
- Roy, Tamal,Barik, Sunirmal,Kumar, Manish,Kureshy, Rukhsana I.,Ganguly, Bishwajit,Khan, Noor-Ul H.,Abdi, Sayed H. R.,Bajaj, Hari C.
-
p. 3899 - 3908
(2015/02/19)
-
- SUBSTITUTED SPIROPYRIDO[1,2-a]PYRAZINE DERIVATIVE AND PHARMACEUTICAL USE OF SAME AS HIV INTEGRASE INHIBITOR
-
Provided is a substituted spiropyrido[1,2-a]pyrazine derivative or a pharmaceutically acceptable salt thereof, which is useful as an anti-HIV agent. The present invention relates to a compound represented by the following formula [I] or [II] or a pharmace
- -
-
Paragraph 1551; 1598; 1599; 1600
(2014/08/19)
-
- A broadly applicable and practical oligomeric (salen)Co catalyst for enantioselective epoxide ring-opening reactions
-
The (salen)Co catalyst (4a) can be prepared as a mixture of cyclic oligomers in a short, chromatography-free synthesis from inexpensive, commercially available precursors. This catalyst displays remarkable enhancements in reactivity and enantioselectivity relative to monomeric and other multimeric (salen)Co catalysts in a wide variety of enantioselective epoxide ring-opening reactions. The application of catalyst 4a is illustrated in the kinetic resolution of terminal epoxides by nucleophilic ring-opening with water, phenols, and primary alcohols; the desymmetrization of meso epoxides by addition of water and carbamates; and the desymmetrization of oxetanes by intramolecular ring opening with alcohols and phenols. The favorable solubility properties of complex 4a under the catalytic conditions facilitated mechanistic studies, allowing elucidation of the basis for the beneficial effect of oligomerization. Finally, a catalyst selection guide is provided to delineate the specific advantages of oligomeric catalyst 4a relative to (salen)Co monomer 1 for each reaction class.
- White, David E.,Tadross, Pamela M.,Lu, Zhe,Jacobsen, Eric N.
-
p. 4165 - 4180
(2014/06/09)
-
- NaHSO3-Promoted ring openings of n-tosylaziridines and epoxides with H2O
-
NaHSO3-oriented ring openings of a wide variety of N-tosylaziridines and epoxides with H2O under mild conditions in acetone was found to be a convenient and effective method, which provided the desired ss-aminoalcohols and ss-diols in good to excellent yields and with uniformly high regioselectivity.
- Li, Xing,Ni, Bin,Chang, Hong-Hong,Wei, Wen-Long
-
p. 1009 - 1015
(2014/04/17)
-