- Assessing the pKa-Dependent Activity of Hydroxyl Hydrogen Bond Donors in the Organocatalyzed Cycloaddition of Carbon Dioxide to Epoxides: Experimental and Theoretical Study
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The development of hydrogen bond donors (HBDs) as catalytic moieties in the cycloaddition of carbon dioxide to epoxides is an active field of research to access efficient, inexpensive and sustainable metal-free systems for the conversion of carbon dioxide to useful chemicals. Thus far, no systematic attempt to correlate the activity of a diverse selection of HBDs to their physico-chemical properties has been undertaken. In this work, we investigate factors influencing the catalytic activity of hydroxyl HBDs from different chemical families under ambient conditions by considering the HBDs Br?nsted acidity (expressed as pKa), the number of hydroxyls and structural aspects. As an effect, this study highlights the crucial role of the hydroxyl protons’ Br?nsted acidity in determining the catalytic activity of the HBDs, identifies an ideal range for the hydroxyl HBDs proton acidity (9 a 11) and leads to a revaluation of phenol and to the discovery of a simple ascorbic acid derivative as efficient HBDs for the title cycloaddition reaction. Density functional theory (DFT) calculations show mild reactions barriers for the reaction catalysed by phenol and suggest the occurrence of aggregation between molecules of ascorbic acid as a further factor affecting catalytic activity. (Figure presented.).
- Yingcharoen, Prapussorn,Kongtes, Chutima,Arayachukiat, Sunatda,Suvarnapunya, Kittipong,Vummaleti, Sai V. C.,Wannakao, Sippakorn,Cavallo, Luigi,Poater, Albert,D' Elia, Valerio
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- Discovery of a stable vitamin C glycoside in crab apples (Malus sylvestris)
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Non-targeted LC-MS metabolomics on fruit of three wild and domesticated apple species (Malus sylvestris, M. sieversii and M. domestica) showed that two crab apple (M. sylvestris) accessions were distinguished by high concentrations of an ascorbic acid glycoside (AAG). This was partly purified, but key NMR signals were masked by inseparable sucrose. Reference samples of 2-O-β-D-glucopyranosyl L-ascorbic acid and 2-O-β-D-galactopyranosyl L-ascorbic acid were synthesised, but both coincided with the crab apple AAG on LC-MS. Peracetylation of the crab apple extract allowed both purification and characterisation, and the AAG was proven to be 2-O-β-D-glucopyranosyl L-ascorbic acid by comparison of 1H NMR, HRMS and HPLC data with synthesised peracetylated ascorbyl glycoside standards. The stability of the natural AA 2-β-glycoside was similar to synthetic 2-O-α-D-glucopyranosyl L-ascorbic acid, used widely in cosmetic and pharmaceutical products. This discovery in crab apples (Rosaceae) is only the fourth reported occurrence of any ascorbyl glycoside from plants, the others being from Cucurbitaceae, Solanaceae and Brassicaceae. It is hypothesised that AAGs may be more widespread in plants than currently realised.
- Richardson, Alistair T.,Cho, Jung,McGhie, Tony K.,Larsen, David S.,Schaffer, Robert J.,Espley, Richard V.,Perry, Nigel B.
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- Synthesis of new L-ascorbic ferulic acid hybrids
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A feasibility and chemical study of the coupling conditions of L-ascorbic acid with ferulic acid derivatives are described on the basis of the known synergistic effects of mixtures of various antioxidants. Novel L-ascorbic ferulic hybrids linked at the C-3 hydroxyl group were prepared with the aim to protect the alcohol function and the enediol system.
- Voisin-Chiret, Anne Sophie,Bazin, Marc-Antoine,Lancelot, Jean-Charles,Rault, Sylvain
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- Biosynthesis-Inspired Approach to Kujounin A2 Using a Stereoselective Tsuji-Trost Alkylation
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A new biosynthesis was proposed for the kujounins A1 and A2 beginning from ascorbic acid, which in turn inspired a synthetic approach to kujounin A2. The ring system was assembled in two steps using a stereoselective Tsuji-Trost reaction followed by ozonolysis. The chemically labile disulfide was introduced in several more steps. These results will make kujounin and its analogues available for further evaluation.
- Burtea, Alexander,Rychnovsky, Scott D.
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- Design, synthesis, and neuroprotective effects of dual-brain targeting naproxen prodrug
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A new dual-targeting naproxen prodrug conjugated with glucose and ascorbic acid for central nervous system (CNS) drug delivery was designed and synthesized in order to effectively deliver naproxen to the brain. Naproxen could be released from the prepared prodrugs when incubated with various buffers, mouse plasma, and brain homogenate. Also, the prodrug showed superior neuroprotective effect in vivo over naproxen. Our results suggest that chemical modification of therapeutics with warheads of glucose and ascorbic acid represents a promising and efficient strategy for the development of brain targeting prodrugs by utilizing the endogenous transportation mechanism of the warheads.
- Wang, Linhui,Zhang, Li,Zhao, Yi,Fu, Qiuyi,Xiao, Wenjiao,Lu, Runxin,Hai, Li,Guo, Li,Wu, Yong
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- Ascorbic acid-based inhibitors of α-amylases
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A series of ascorbic acid and isoascorbic acid derivatives has been evaluated as inhibitors of malt, bacterial, fungal, pancreatic and salivary α-amylase inhibition. Acylation of the primary and scondary alcohols, and the absolute configuration of the secondary alcohol, do not affect the potency of inhibition.
- Abell, Andrew D.,Ratcliffe, Maureen J.,Gerrard, Juliet
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- 1,4-Dioxane-2,5-dione-type monomers derived from l-ascorbic and d-isoascorbic acids. Synthesis and polymerisation
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l-Ascorbic and d-isoascorbic acids have been used as the starting materials for the preparation of (3R,4′S)-3-(2′,2′-dimethyl-1′,3′-dioxolan-4′-yl)-1,4-dioxane-2,5-dione (IPTA), (3R and S, 4′S,6R)-3-methyl-6-(2′,2′-dimethyl-1′,3′-dioxolan-4′-yl)-1,4-dioxane-2,5-dione (IPTP) and (3R,4′R)-3-(2′,2′-dimethyl-1′,3′-dioxolan-4′-yl)-1,4-dioxane-2,5-dione (IPEA), three novel 1,4-dioxane-2,5-dione-type monomers. Ring-opening homopolymerisation and copolymerisation of the IPTA monomer, derived from l-ascorbic acid, with d,l-lactide have been performed. The polymers were characterised by elemental microanalysis, as well as IR and 1H and 13C NMR spectroscopies. GPC was used to estimate product molecular weights, and thermal studies (DSC and TGA) revealed that all the polymers were amorphous, being stable up to 250 °C under nitrogen.
- Bueno, Manuel,Molina, Inmaculada,Galbis, Juan A.
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- A New Convenient Method for the Synthesis of Chiral C3-Synthons
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Routes are described for the facile preparation of protected optically pure D- and L-glyceric acid (1a,b; 2a,b) starting from D-mannitol, D-isoascorbic acid and L-ascorbic acid.The key step is a ruthenium catalyzed oxidative cleavage of the vicinal diols 4a,b or the α-hydroxy acids 7a,b; 10a,b.
- Emons, Carry H.H.,Kuster, Ben F.M.,Vekemans, Jozef A.J.M.,Sheldon, Roger A.
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- Enhanced delivery of γ-secretase inhibitor DAPT into the brain via an ascorbic acid mediated strategy
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Inhibition of γ-secretase, one of the enzymes responsible for the cleavage of the amyloid precursor protein (APP) to produce pathogenic Aβ peptides, is an attractive approach for the treatment of Alzheimer's disease. We designed a γ-secretase inhibitor bearing an ascorbic acid moiety which allows a specific delivery of the drug to the brain. Through, on the one hand, Aβ peptide production measurements by specific in vitro assays (γ-secretase cell free assay and cell based assay on HEK 293 APP transfected cells) and on the other hand through pharmacokinetic studies on animal models, the new inhibitor shows a good pharmacokinetic profile as well as a potent γ-secretase inhibitory activity In vitro. From the obtained results, it is expected that drug 2 will be mainly delivered to the CNS with a low diffusion in the peripheral tissues. Consequently the side effects of this γ-secretase inhibitor on the immune cells could be reduced. The Royal Society of Chemistry 2005.
- Quelever, Gilles,Kachidian, Philippe,Melon, Christophe,Garino, Cedrik,Laras, Younes,Pietrancosta, Nicolas,Sheha, Mahmoud,Kraus, Jean Louis
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- Site-Selective Photochemical Fluorination of Ketals: Unanticipated Outcomes in Selectivity and Stability
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We report a method for the regioselective photochemical sp3 C-H fluorination of acetonide ketals that presents interesting problems in chemical reactivity. The question of why certain products of the reaction are stable while others are not is addressed, as is the question of why only select α-ethereal hydrogen atoms are targeted in the reaction. We demonstrate that the method can be employed to synthesize unprecedented fluorinated sugars and steroids, and it can also be applied toward the fluorination of carbamates. Though some substrates contain up to eight discrete α-ethereal C-H bonds, we observed site-selectivity in each case, prompting us to investigate potential transition states for the reaction. Finally, a remarkable regiochemical switch upon minor structural modification of a diketal is also analyzed.
- Capilato, Joseph N.,Pitts, Cody Ross,Rowshanpour, Rozhin,Dudding, Travis,Lectka, Thomas
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- Initial biological evaluations of 18F-KS1, a novel ascorbate derivative to image oxidative stress in cancer
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Background: Reactive oxygen species (ROS)-induced oxidative stress damages many cellular components such as fatty acids, DNA, and proteins. This damage is implicated in many disease pathologies including cancer and neurodegenerative and cardiovascular diseases. Antioxidants like ascorbate (vitamin C, ascorbic acid) have been shown to protect against the deleterious effects of oxidative stress in patients with cancer. In contrast, other data indicate potential tumor-promoting activity of antioxidants, demonstrating a potential temporal benefit of ROS. However, quantifying real-time tumor ROS is currently not feasible, since there is no way to directly probe global tumor ROS. In order to study this ROS-induced damage and design novel therapeutics to prevent its sequelae, the quantitative nature of positron emission tomography (PET) can be harnessed to measure in vivo concentrations of ROS. Therefore, our goal is to develop a novel translational ascorbate-based probe to image ROS in cancer in vivo using noninvasive PET imaging of tumor tissue. The real-time evaluations of ROS state can prove critical in developing new therapies and stratifying patients to therapies that are affected by tumor ROS. Methods: We designed, synthesized, and characterized a novel ascorbate derivative (E)-5-(2-chloroethylidene)-3-((4-(2-fluoroethoxy)benzyl)oxy)-4-hydroxyfuran-2(5H)-one (KS1). We used KS1 in an in vitro ROS MitoSOX-based assay in two different head and neck squamous cancer cells (HNSCC) that express different ROS levels, with ascorbate as reference standard. We radiolabeled 18F-KS1 following 18F-based nucleophilic substitution reactions and determined in vitro reactivity and specificity of 18F-KS1 in HNSCC and prostate cancer (PCa) cells. MicroPET imaging and standard biodistribution studies of 18F-KS1 were performed in mice bearing PCa cells. To further demonstrate specificity, we performed microPET blocking experiments using nonradioactive KS1 as a blocker. Results: KS1 was synthesized and characterized using 1H NMR spectra. MitoSOX assay demonstrated good correlations between increasing concentrations of KS1 and ascorbate and increased reactivity in SCC-61 cells (with high ROS levels) versus rSCC-61cells (with low ROS levels). 18F-KS1 was radiolabeled with high radiochemical purity (> 94%) and specific activity (~ 100 GBq/μmol) at end of synthesis (EOS). Cell uptake of 18F-KS1 was high in both types of cancer cells, and the uptake was significantly blocked by nonradioactive KS1, and the ROS blocker, superoxide dismutase (SOD) demonstrating specificity. Furthermore, 18F-KS1 uptake was increased in PCa cells under hypoxic conditions, which have been shown to generate high ROS. Initial in vivo tumor uptake studies in PCa tumor-bearing mice demonstrated that 18F-KS1 specifically bound to tumor, which was significantly blocked (threefold) by pre-injecting unlabeled KS1. Furthermore, biodistribution studies in the same tumor-bearing mice showed high tumor to muscle (target to nontarget) ratios. Conclusion: This work demonstrates the strong preliminary support of 18F-KS1, both in vitro and in vivo for imaging ROS in cancer. If successful, this work will provide a new paradigm to directly probe real-time oxidative stress levels in vivo. Our work could enhance precision medicine approaches to treat cancer, as well as neurodegenerative and cardiovascular diseases affected by ROS.
- Solingapuram Sai, Kiran Kumar,Bashetti, Nagaraju,Chen, Xiaofei,Norman, Skylar,Hines, Justin W.,Meka, Omsai,Kumar, J. V. Shanmukha,Devanathan, Sriram,Deep, Gagan,Furdui, Cristina M.,Mintz, Akiva
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- Cyclohexyl Spiro-Fused α-Hydroxy Tetronic Acid Derivatives From Vitamin C
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The reaction of dienophile 4, prepared from L-ascorbic acid in 5 steps, with various dienes to prepare cyclohexyl spiro-fused α-hydroxy tetronic acid derivatives is reported.
- Poss, A. J.,Brodowski, M. H.
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- Antiallergic activity of 6-deoxy-2-o-methyl-6-(N-hexadecanoyl)amino-l-ascorbic acid
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Allergy is an excessive immune response to a specific antigen. Type I allergies, such as hay fever and food allergies, have increased significantly in recent years and have become a worldwide problem. We previously reported that an ascorbic acid derivative having palmitoyl and glucosyl groups, 2-O-α-D-glucopyranosyl-6-O-hexadecanoyl-L-ascorbic acid (6-sPalm-AA-2G), showed inhibitory effects on degranulation in vitro and on the passive cutaneous anaphylaxis (PCA) reaction in mice. In this study, several palmitoyl derivatives of ascorbic acid were synthesized and a structure–activity relationship study was performed to discover more potent ascorbic acid derivatives with degranulation inhibitory activity. 6-Deoxy-2-O-methyl-6-(N-hexadecanoyl)amino-L-ascorbic acid (2-Me-6-N-Palm-AA), in which a methyl group was introduced into the hydroxyl group at the C-2 position of ascorbic acid and in which the hydroxyl group at the C-6 position was substituted with an N-palmitoyl group, exhibited much higher inhibitory activity for degranulation in vitro than did 6-sPalm-AA-2G. 2-Me-6-N-Palm-AA strongly inhibit the PCA reaction in mice at lower doses than those of 6-sPalm-AA-2G. These findings suggest that 2-Me-6-N-Palm-AA may be a promising therapeutic candidate for allergic diseases.
- Ito, Hideyuki,Iwaoka, Yuji,Matsuno, Hiroaki,Miura, Kaori,Tai, Akihiro
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- α-Tocopherol-ascorbic acid hybrid antioxidant based cationic amphiphile for gene delivery: Design, synthesis and transfection
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Natural antioxidants and vitamins have potential to protect biological systems from peroxidative damage induced by peroxyl radicals, α-tocopherol (Vitamin E, lipid soluble) and ascorbic acid (vitamin C, water soluble), well known natural antioxidant molecules. In the present study we described the synthesis and biological evaluation of hybrid of these two natural antioxidants with each other via ammonium di-ethylether linker, Toc-As in gene delivery. Two control cationic lipids N14-As and Toc-NOH are designed in such a way that one is with ascorbic acid moiety and no tocopherol moiety; another is with tocopherol moiety and no ascorbic acid moiety respectively. All the three cationic lipids can form self-assembled aggregates. The antioxidant efficiencies of the three lipids were compared with free ascorbic acid. The cationic lipids (Toc-As, N14-As and Toc-NOH) were formulated individually with a well-known fusogenic co-lipid DOPE and characterization studies such as DNA binding, heparin displacement, size, charge, circular dichroism were performed. The biological characterization studies such as cell viability assay and in vitro transfection studies were carried out with the above formulations in HepG2, Neuro-2a, CHO andHEK-293T cell lines. The three formulations showed their transfection efficiencies with highest in Toc-As, moderate inN14-As and least in Toc-NOH. Interestingly, the transfection efficiency observed with the antioxidant based conjugated lipid Toc-As is found to be approximately two and half fold higher than the commercially available lipofectamine 2000 at 4:1 charge ratio in Hep G2 cell lines. In the other cell lines studied the efficiency of Toc-As is found to be either higher or similarly active compared to lipofectamine 2000. The physicochemical characterization results show that Toc-As lipid is showing maximum antioxidant potency, strong binding with pDNA, least size and optimal zeta potential. It is also found to be least toxic in all the cell lines studied especially in Neuro-2a cell lines when compared to other two lipids. In summary, the designed antioxidant lipid can be exploited as a delivering system for treating ROS related diseases such as malignancy, brain stroke, etc.
- Muripiti, Venkanna,Brijesh, Lohchania,Rachamalla, Hari Krishnareddy,Marepally, Srujan Kumar,Banerjee, Rajkumar,Patri, Srilakshmi V.
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- Synthesis and Biological Evaluation of Ascorbyl-Conjugated Peptide Derivatives as Collagen Synthesis Stimulating Agents in Human Skin Fibroblasts
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Vitamin C (ascorbic acid) is a widely used agent for anti-aging and whitening in the field of cosmetics. It affects collagen production in skin cells, inhibits melanin synthesis, displays anti-oxidant activity, and improves the immune system. However, vitamin C has limitations in cell permeability and environmental condition such as heating and lighting decrease its stability. Thus, vitamin C derivatives are being developed to overcome these problems. In this study, we synthesized vitamin C derivatives with a succinoyl group at the 2-position and peptides in the form of ester bonds. We then evaluated the cytotoxicity and collagen synthesis activity of these new compounds in human skin fibroblasts. Vitamin C-conjugated peptides were also synthesized in ether and carbamate forms, and the optimal combination conditions of vitamin C and peptides were identified. In addition, collagen synthesis-stimulating activity of vitamin C-conjugated peptides was also evaluated and compared to the effects of vitamin C alone. Based on these results, we confirmed that the ester-bonded vitamin C-conjugated peptide GEKG showed more stimulating effect on the production of collagen and related gene expression than either vitamin C or GEKG alone. This study will provide important information for developing skin health products and other topical cosmetics using vitamin C and peptides.
- Park, Kyeong-Yong,Kim, Jiyeon
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- Mint leaf derived carbon dots for dual analyte detection of Fe(iii) and ascorbic acid
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Highly luminescent carbon dots (CDs) are obtained from mint leaves adopting a simple and cost effective route devoid of additional chemical reagents and functionalization. The as-synthesized CDs are characterized by TEM, FE-SEM, XRD analysis, FTIR, Raman, UV-visible and photoluminescence spectral studies. The results reveal that the CDs have an average diameter of 4 nm with a hydroxyl-rich surface. The luminescence of the dots was excitation dependent and was stable towards variation in the medium. The system could perform as a promising on-off-on fluorescent sensor for the selective and sensitive dual analyte recognition of Fe3+ and AA with a detection limit of 374 nM and 79 nM, respectively. The mechanism of ascorbic acid sensing by the CD-Fe3+ unit is established by identifying the binding sites of the biomolecule with the metal ion by examining the behaviour of the sensor in the presence of ascorbic acid derivatives.
- Raveendran, Varsha,Suresh Babu, Adukamparai Rajukrishnan,Renuka, Neeroli Kizhakayil
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- Novel multifunctional ascorbic triazole derivatives for amyloidogenic pathway inhibition, anti-inflammation, and neuroprotection
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Alzheimer’s disease (AD) is a common neurodegenerative disorder. The number of patients with AD is projected to reach 152 million by 2050. Donepezil, rivastigmine, galantamine, and memantine are the only four drugs currently approved by the United States Food and Drug Administration for AD treatment. However, these drugs can only alleviate AD symptoms. Thus, this research focuses on the discovery of novel lead compounds that possess multitarget regulation of AD etiopathology relating to amyloid cascade. The ascorbic acid structure has been designated as a core functional domain due to several characteristics, including antioxidant activities, amyloid aggregation inhibition, and the ability to be transported to the brain and neurons. Multifunctional ascorbic derivatives were synthesized by copper (I)-catalyzed azide–alkyne cycloaddition reaction (click chemistry). The in vitro and cell-based assays showed that compounds 2c and 5c exhibited prominent multifunctional activities as beta-secretase 1 inhibitors, amyloid aggregation inhibitors, and antioxidant, neuroprotectant, and anti-inflammatory agents. Significant changes in activities promoting neuroprotection and anti-inflammation were observed at a considerably low concentration at a nanomolar level. Moreover, an in silico study showed that compounds 2c and 5c were capable of being permeated across the blood–brain barrier by sodium-dependent vitamin C transporter-2.
- Chauthong, Nattapong,Jiaranaikulwanitch, Jutamas,Jiranusornkul, Supat,Nilkosol, Supitcha,Pandith, Hataichanok,Tadtong, Sarin,Thammarat, Phanit,Vajragupta, Opa
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supporting information
(2021/06/15)
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- a method for manufacturing 3-O-alkyl-ascorbic acid
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3 - O - Alkyl - ascorbic acid. 3 - O -alkyl - ascorbic acid having a low reaction temperature and a high yield. Provided is a process for preparing 3 - O - alkyl - ascorbic acid having a low reaction temperature and simple preparation process and high yield.
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Paragraph 0130-0132; 0146-0150
(2021/12/03)
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- Synthesis of l-ascorbic acid-amino acid-norcantharidin conjugates and their biological activity evaluation in vitro
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Three components of L-ascorbic acid, amino acid and functionalized norcantharidins were constructed together in several steps to form 42 norcantharidin derivatives in a high yield. The structure of these synthesized l-ascorbic acid-amino acid-norcantharidin conjugates are determined by 1HNMR, 13CNMR and MS spectrum. The results showed that compounds 6e, 6g, 6j, 6l, 6m, 6b, 6e, 6i, and 6n showed high cytotoxicity to HepG2 and compounds 6b, 6e-g, 6l, 6n, 7b, 7d, 7h, 7i, 7n, 8g, 8i exhibited high cytotoxicity to SW480; Meanwhile, besides 6b, 6e, 6g, and 6k, the other compounds showed less toxic to LO2 at a concentration of 50 μg/mg after 72 h. Compound 6g can induce Mφ-type macrophages derived from mouse bone marrow to polarize to M1-type macrophages.
- Wang, Xianheng,Wu, Caoyuan,Zhang, Jidong,Zhao, Changkuo,Zhou, Yiqi
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supporting information
(2022/01/06)
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- COMPOUND, ANTI-ALLERGY DRUG, AND MEDIATOR RELEASE INHIBITOR
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A compound represented by the following formula has a high anti-allergy activity. R1 represents a substituted or unsubstituted acyloxy group, or a substituted or unsubstituted acylamino group, R2 represents a substituted or unsubstituted alkyl group.
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Paragraph 0062-0063
(2021/07/17)
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- Cosmetic composition having the effect of promoting collagen synthesis and inhibiting reactive oxygen species
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The present invention relates to a novel compound ascombi and its use for improving wrinkles.
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Paragraph 0068; 0103; 0106
(2021/06/22)
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- Preparation process of ascorbyl ethyl ether
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The invention relates to a preparation process of ascorbyl ethyl ether. The preparation process comprises the following steps: with ascorbic acid and acetone as raw materials, carrying out reacting for 8-10 hours under the catalysis of oxalyl chloride, and then carrying out filtering, washing and drying to obtain 5,6-O-isopropylidene-L-ascorbic acid; adding alkaline-earth metal oxide into mother liquor to remove oxalic acid, hydrogen chloride and moisture, and drying acetone with a molecular sieve for reuse; dissolving an ethylation reagent, inorganic base and 5,6-O-isopropyl-L-ascorbic acid in ethanol, carrying out reacting for 6-8 hours at 40-60 DEG C, and carrying out purifying to obtain 3-ethyl-5,6-O-isopropyl-L-ascorbic acid; removing isopropyl protecting groups through an alcohol solution of hydrogen chloride, carrying out concentrating, adding a solvent with low solubility, and conducting recrystallizing to obtain the ascorbyl ethyl ether. The process solves problems in recoveryand reuse of acetone, does not use toxic and harmful solvents and organic alkali, does not produce a large amount of waste liquid, and is economic and environment-friendly; technological process is easy to control; and the process is high in yield and easy to industrially popularize.
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Paragraph 0049-0054
(2020/08/30)
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- Method for synthesizing 3-O-alkyl-5,6-O-isopropylidene ascorbic acid by using circulation method
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The invention provides a method for synthesizing 3-O-alkyl-5,6-O-isopropylidene ascorbic acid by using a circulation method. The method comprises the following steps: enabling excessive 5,6-O-isopropylidene-ascorbic acid to react with an alkali and an alkyl reagent in a high-boiling-point polar aprotic solvent; after the reaction is completed, performing extraction with a low-polarity aprotic solvent; performing water washing treatment on the low-polarity aprotic solvent extraction liquid; performing concentration so as to obtain 3-O-alkyl-5,6-O-isopropylidene ascorbic acid; supplementing thealkali and the alkyl solvent into the high-boiling-point polar aprotic solvent extraction residue liquid; continuing a next batch of reactions for synthesizing the 3-O-alkyl-5,6-O-isopropylidene ascorbic acid; and performing deprotection on the 3-O-alkyl-5,6-O-isopropylidene ascorbic acid, so as to obtain 3-O-alkyl ascorbic acid. The method is good in selectivity, complete in raw material reaction, high in total yield and free of organic waste emission and has great industrial application values, and the synthesis cost can be greatly reduced.
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Paragraph 0024-0025
(2019/10/29)
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- Synthesis of a diastereomer of the marine macrolide lytophilippine A
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The synthesis of a diastereomer of lytophilippine A required 22 longest linear steps using known building blocks. Cross-metathesis/asymmetric aldol addition and regioselective esterification/ring-closing metathesis served as efficient combi tools for scaffold construction. Detailed NMR investigations in different solvent (systems) provide evidence for a deep-seated configurational misassignment of the molecule named lytophilippine A.
- Klüppel, André,Gille, Annika,Karayel, Ceren Ester,Hiersemann, Martin
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supporting information
p. 2421 - 2425
(2019/03/29)
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- Synthesis of C1–C11 eribulin fragment and its diastereomeric analogues
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A practical stereoselective synthesis of the central C1–C10 fragment of eribulin and its two diastereomeric analogues is developed. Our approach relied on the use of L-ascorbic acid as the starting material which allowed accessing a key intermediate with a syn diol moiety (C9 and C10 of eribulin) and a carboxylic ester group. A functionalized six membered lactone having several required hydroxyl groups was then obtained. In a number of steps, the lactone was converted to an intermediate for our key oxa-Michael reaction. A regio- and stereocontrolled intramolecular oxa-Michael reaction completed the synthesis of the C1–11 fragment having a trans-fused tetrahydropyrans with the exact stereochemistry of various hydroxyl groups, as in eribulin.
- Khatravath, Mahender,Mallurwar, Naveen Kumar,Konda, Saidulu,Gaddam, Jagan,Rao, Pallavi,Iqbal, Javed,Arya, Prabhat
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supporting information
(2019/07/17)
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- Antitumor and antiviral activities of 4-substituted 1,2,3-triazolyl-2,3-dibenzyl-L-ascorbic acid derivatives
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Two series of 6-(1,2,3-triazolyl)-2,3-dibenzyl-L-ascorbic acid derivatives with the hydroxyethylene (8a?8u) and ethylidene linkers (10c?10p) were synthesized and evaluated for their antiproliferative activity against seven malignant tumor cell lines and antiviral activity against a broad range of viruses. Conformationally unrestricted spacer between the lactone and 1,2,3-triazole units in 8a?8u series had a profound effect on antitumor activity. Besides, the introduction of a long side chain at C-4 of 1,2,3-triazole that led to the synthesis of decyl-substituted 2,3-dibenzyl-L-ascorbic acid 8m accounted for a selective and potent antiproliferative activity on breast cancer MCF-7 cells cells in the nM range. Further analysis showed that compound 8m strongly enhanced expression of hypoxia inducible transcription factor 1 α (HIF-1α) and to some extent decreased expression of nitric oxide synthase 2 (NOS2) suggesting its role in regulating HIF-1α signalling pathway. The p-methoxyphenyl-substituted derivative 10g displayed specific anti-cytomegalovirus (CMV) potential, whereas aliphatic-substituted derivatives 8l and 8m had the most potent, yet relatively non-specific, anti-varicella-zoster (VZV) activity.
- Macan, Andrijana Me??i?,Harej, Anja,Cazin, Ines,Klobu?ar, Marko,Stepani?, Vi?nja,Paveli?, Kre?imir,Paveli?, Sandra Kraljevi?,Schols, Dominique,Snoeck, Robert,Andrei, Graciela,Rai?-Mali?, Silvana
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- Crystal form A of 3-O-ethyl-L-ascorbic acid, its preparation method and whitening composition
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The present invention relates to the field of crystals and in particular, to a crystal form A of 3-O-ethyl-L-ascorbic acid, its preparation method and a whitening composition. The characteristic peaksof the crystal form A of 3-O-ethyl-L-ascorbic acid are characterized by X-ray diffraction pattern and prove that the crystal form A is formed. The crystal form A has good stability, especially excellent thermal stability and long-term storage stability.
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Paragraph 0054; 0061; 0062
(2019/10/17)
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- Design, synthesis and biological evaluation of C(4) substituted monobactams as antibacterial agents against multidrug-resistant Gram-negative bacteria
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A series of novel pyridone conjugated monobactams with various substituents at the (4) position were synthesized and evaluated for their antibacterial activities against a panel of multidrug-resistant (MDR) Gram-negative bacteria in vitro. Compounds 46d, 54 and 75e displayed good to moderate activities against P. aeruginosa, among which the activity of 75e against P. aeruginosa was comparable to that of BAL30072 under iron limitation condition. Compounds 35, 46d, 54, 56a, 56c and 56d exhibited good to excellent antibacterial activities against E. coli and K. pneumoniae, which were comparable or superior to that of BAL30072. In vitro liver microsomal stability was further evaluated and the results manifested that Compounds 35, 46d and 54 were metabolically stable in human liver microsomes.
- Kou, Qunhuan,Wang, Ting,Zou, Feng,Zhang, Shuhua,Chen, Qian,Yang, Yushe
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supporting information
p. 98 - 109
(2018/04/05)
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- Dual-targeting for brain-specific liposomes drug delivery system: Synthesis and preliminary evaluation
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The treatment of glioma has become a great challenge because of the existence of brain barrier (BB). In order to develop an efficient brain targeting drug delivery system to greatly improve the brain permeability of anti-cancer drugs, a novel brain-targeted glucose-vitamin C (Glu-Vc) derivative was designed and synthesized as liposome ligand for preparing liposome to effectively deliver paclitaxel (PTX). The liposome was prepared and its particle size, zeta potential, encapsulation efficiency, release profile, stability, hemolysis and cytotoxicity were also characterized. What's more, the cellular uptake of CFPE-labeled Glu-Vc-Lip on GLUT1- and SVCT2-overexpressed C6 cells was 4.79-, 1.95-, 4.00- and 1.53-fold higher than that of Lip, Glu-Lip, Vc-Lip and Glu + Vc-Lip. Also, the Glu-Vc modified liposomes showed superior targeting ability in vivo evaluation compared with naked paclitaxel, non-coated, singly-modified and co-modified by physical blending liposomes. The relative uptake efficiency was enhanced by 7.53 fold to that of naked paclitaxel, while the concentration efficiency was up to 7.89 times. What's more, the Glu-Vc modified liposomes also displayed the maximum accumulation of DiD-loaded liposomes at tumor sites with the strongest fluorescence in the brain in vivo imaging. Our results suggest that chemical modification of liposomes with warheads of glucose and vitamin C represents a promising and efficient strategy for the development of brain-specific liposomes drug delivery system by utilizing the endogenous transportation mechanism of the warheads.
- Peng, Yao,Zhao, Yi,Chen, Yang,Yang, Zhongzhen,Zhang, Li,Xiao, Wenjiao,Yang, Jincheng,Guo, Li,Wu, Yong
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p. 4677 - 4686
(2018/08/11)
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- REDOX POLYMERIZABLE COMPOSITION WITH PHOTOLABILE REDUCING AGENTS
-
Polymerizable compositions comprising a redox initiator system is disclosed. The redox initiators comprises a photolabile reducing agent, that photolyzes and initiates the redox cycle. Dental compositions comprising dental resins and the photolabile redox initiator system are also described.
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Page/Page column 53
(2017/09/02)
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- A 2 - O - (2, 3, 4, 6 - four - O - acetyl - beta - D - glucopyranosyl) - 3 - O - benzyl - 5, 6 - O - isopropylidene - hematic preparation method
-
The invention relates to a preparation method of 2-O-(2, 3, 4, 6-tetra-O-acetyl-Beta-D-glucopyranosyl)-3-O-benzyl-5, 6-isopropylidene-ascorbic acid. The preparation method includes: under catalysis of p-toluenesulfonic acid and under the condition of ice bath, allowing vitamin C and acetone to react for 3-5h, and performing filtering, washing and drying to obtain white solid of 5, 6-O-isopropylidene-L-ascorbic acid; adding mixture of benzyl bromide, alkali and the white solid of the 5, 6-O-isopropylidene-L-ascorbic acid into solvent, performing heating to allow reflux reaction for 3-5h, and washing and purifying reaction liquid to obtain 3-O-benzyl-5, 6-O-isopropylidene-L-ascorbic acid; dissolving the 3-O-benzyl-5, 6-O-isopropylidene-L-ascorbic acid with dichloromethane, dropwise adding dissolved solution into sodium hydroxide solution containing phase-transfer catalysts such as 2, 3, 4, 6-tetra-O-acetyl-Alpha-glucopyranosyl bromide and quaternary ammonium salts, and allowing reaction to obtain a product. The preparation method has the advantages that raw materials are easy to obtain, reaction conditions are moderate, the synthetic process is easy to control, yield is high, and the method has important applicable value.
- -
-
Paragraph 0018
(2017/07/12)
-
- Continuous flow-ultrasonic synergy in click reactions for the synthesis of novel 1,2,3-triazolyl appended 4,5-unsaturated l-ascorbic acid derivatives
-
A combination of flow chemistry and batch-based synthetic procedures has been successfully applied to the assembly of novel 4,5-unsaturated l-ascorbic acid series 6a-6n with diverse C-6-substituted 1,2,3-triazole moiety. We report herein the first Cu(i)-catalyzed 1,3-dipolar cycloaddition of azido functionalized l-ascorbic acid derivative and selected alkynes to provide target 1,2,3-triazolyl appended 4,5-didehydro-5,6-dideoxy-l-ascorbic acid library 6a-6n under both micro-flow and batch conditions. Implementation of ultrasound with flow chemistry accelerated hour-scale reaction conditions in batch to the minute range in micro-flow device and considerably improved the yields for the flow syntheses of 6a-6n. Moreover, the synergistic use of microreactor technology and ultrasonic irradiation highlights the sustainable eco-friendly aspect of utilized method.
- Me??i?, Andrijana,?ali?, Anita,Gregori?, Tomislav,Zeli?, Bruno,Rai?-Mali?, Silvana
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p. 791 - 800
(2017/01/13)
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- Manufacturing method of Pyridoxine derivatives combined with Ascorbic acid
-
The present invention relates to a production method of a pyridoxine derivative combined with ascorbic acid. The pyridoxine derivative produced by the method of the present invention has a structure which combines a pyridoxine intermediate product in which an acetyl group is bonded to a hydroxyl group at the third position of ascorbic acid, vitamin C, thereby showing an effect of vitamin C as well as an effect of vitamin B6, has antioxidant and skin whitening effects by effectively improving low oxidation stability of vitamin C, has greatly low cytotoxicity, and has excellent stability.COPYRIGHT KIPO 2017
- -
-
Paragraph 0116; 0123-0125
(2017/04/25)
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- Geldanamycin-inspired compounds induce direct trans-differentiation of human mesenchymal stem cells to neurons
-
Inspired from geldanamycin, the synthesis of a new series of 20-membered macrocyclic compounds is developed. The key features in our design are (i) retention of the fragment having the precise chiral functional groups of geldanamycin at C10, C11, C12 and C14, and (ii) replacement of an olefin moiety with the ester group, and the quinoid sub-structure with the triazole ring. The southern fragment needed for the macrocyclic ring formation was obtained from Evans' syn aldol as the key reaction and with the use of D-mannitol as the cheap source of a chiral starting material. For the synthesis of the northern fragment, we utilized L-ascorbic acid, which provided the desired chiral functional groups at C6 and C7. Further, the chain extension completed the synthesis of the northern fragment. In our approach, the crucial 20 membered macrocyclic ring was formed employing the click chemistry. When tested for their ability to directly trans-differentiate human mesenchymal stem cells to neurons, two novel compounds (20a and 7) from this series were identified and this was further validated by the presence of specific neuronal biomarkers (i.e. nestin, agrin and RTN4).
- Jogula, Srinivas,Soorneedi, Anand Ram,Gaddam, Jagan,Chamakuri, Srinivas,Deora, Girdhar Singh,Indarapu, Ranjith Kumar,Ramgopal, Murali Krishna,Dravida, Subhadra,Arya, Prabhat
-
supporting information
p. 110 - 116
(2017/04/26)
-
- Synthesis and evaluation of novel ascorbyl cinnamates as potential anti-oxidant and antimicrobial agents
-
Abstract: An efficient preparation procedure has been proposed for the synthesis of 5,6-di-O-cinnamyl-l-ascorbic acid ester (5,6-CA–AA) and 2-O-cinnamyl-l-ascorbic acid ester (2-CA–AA) via ascorbic acid (AA) and cinnamic acid (CA), and their anti-oxidant and antibacterial activities were also investigated. Among the factors affecting the synthesis efficiency of 5,6-CA–AA and 2-CA–AA, reaction solvent and substrate molar ratio were very important, resulting in 76 and 54% total yield, respectively. Further studies indicated that 5,6-CA–AA maintained the inherent inhibitory ability of AA in α, α-diphenyl-β-picrylhydrazyl radical scavenging assay. Also, it had stronger scavenging activity against hydroxyl radicals than that of standard tert-butylhydroquinone (EC50: 7.84 vs. 8.38?mM). In addition, 5,6-CA–AA and 2-CA–AA possessed comparable antibacterial activity to that of CA. Significantly, the application of ascorbyl cinnamate could retard the lipid oxidation of peanut oil and pork, and the corresponding perioxide value and thiobarbituric acid reactive substance content decreased by 32.0 and 56.5%, respectively. Moreover, the microbial reproduction of the pork treated with mixed ascorbyl cinnamate was attenuated to some extent. These investigations will pave the way for designing more efficient bifunctional derivatives of AA and CA.
- Hui, Ailing,Wang, Yuan,Zhu, Kaili,Chen, Jingchao,Fan, Qingping,Zhou, An,Zhang, Wencheng,Wu, Zeyu
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p. 5901 - 5916
(2017/09/23)
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- Packaging comprising forms of sodium salt of 4-tert-butyl-N-[4-chloro-2-(1-oxy-pyridine-4-carbonyl)-phenyl]-benzenesulfonamide
-
The invention relates to a packaging comprising a multitude (A) of at least 2 administration units comprising polymorphic trihydrated forms of sodium salt of 4-tert-butyl-N-[4-chloro-2-(1-oxy-pyridine-4-carbonyl)-phenyl]-benzenesulfonamide; or (B) of at least 2 administration units comprising polymorphic solvated or desolvated forms of sodium salt of 4-tert-butyl-N-[4-chloro-2-(1-oxy-pyridine-4-carbonyl)-phenyl]-benzenesulfonamide.
- -
-
Paragraph 0045
(2016/08/29)
-
- PROCESS FOR THE PREPARATION OF [(1 S,2R)-3-[[(4-AMINOPHENYL)SULFONYL] (2-METHYLPROPYL)AMINO]-2-HYDROXY-1 -(PHENYLMETHYL)PROPYL]-CARBAMIC ACID (3R,3AS,6AR)HEXAHYDRO FURO[2,3-B]FURAN-3-YL ESTER AND ITS AMORPHOUS FORM
-
The present invention relates to an improved process for the preparation of [(1 S,2R)-3-[ [(4-aminophenyl)sulfonyl] (2-methylpropyl)amino]-2-hydroxy- 1 -(phenylmethyl)propyl] - carbamic acid (3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl ester compound of formula- 1 represented by the following structural formula:
- -
-
Page/Page column 18
(2017/04/21)
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- Design, synthesis and biological evaluation of novel l-ascorbic acid-conjugated pentacyclic triterpene derivatives as potential influenza virus entry inhibitors
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Since the influenza viruses can rapidly evolve, it is urgently required to develop novel anti-influenza agents possessing a novel mechanism of action. In our previous study, two pentacyclic triterpene derivatives (Q8 and Y3) have been found to have anti-influenza virus entry activities. Keeping the potential synergy of biological activity of pentacyclic triterpenes and l-ascorbic acid in mind, we synthesized a series of novel l-ascorbic acid-conjugated pentacyclic triterpene derivatives (18-26, 29-31, 35-40 and 42-43). Moreover, we evaluated these novel compounds for their anti-influenza activities against A/WSN/33 virus in MDCK cells. Among all evaluated compounds, the 2,3-O,O-dibenzyl-6-deoxy-l-ascorbic acid-betulinic acid conjugate (30) showed the most significant anti-influenza activity with an EC50 of 8.7 μM, and no cytotoxic effects on MDCK cells were observed. Time-of-addition assay indicated that compound 30 acted at an early stage of the influenza life cycle. Further analyses revealed that influenza virus-induced hemagglutination of chicken red blood cells was inhibited by treatment of compound 30, and the interaction between the influenza hemagglutinin (HA) and compound 30 was determined by surface plasmon resonance (SPR) with a dissociation constant of KD = 3.76 μM. Finally, silico docking studies indicated that compound 30 and its derivative 31 were able to occupy the binding pocket of HA for sialic acid receptor. Collectively, these results suggested that l-ascorbic acid-conjugated pentacyclic triterpenes were promising anti-influenza entry inhibitors, and HA protein associated with viral entry was a promising drug target.
- Wang, Han,Xu, Renyang,Shi, Yongying,Si, Longlong,Jiao, Pingxuan,Fan, Zibo,Han, Xu,Wu, Xingyu,Zhou, Xiaoshu,Yu, Fei,Zhang, Yongmin,Zhang, Liangren,Zhang, Lihe,Zhou, Demin,Xiao, Sulong
-
supporting information
p. 376 - 388
(2016/02/18)
-
- NOVEL COMPOUND AND MIXTURE COMPOSITION OF THE SAME
-
PROBLEM TO BE SOLVED: To provide an external composition which solves various problems of a current external preparation used for improvement of skin diseases which has heretofore been regarded as a problem.SOLUTION: Provided is an external composition comprising a compound represented by the following formula. Specifically, provided is an external preparation such as a cosmetic, a medicinal drug, and a quasi drug containing a novel compound represented by the following formula and the like, which exhibits a free radical inhibitory action, an anti-wrinkle action, an anti-pimple action, a moisture-retaining action, a barrier function enhancing action, an ultraviolet-derived inflammation inhibitory action of the skin, and is stable and safe.EFFECT: The external composition has a strong whitening action, a free radical inhibitory action, an anti-wrinkle action, an anti-pimple action, a moisture-retaining action, a barrier function enhancing action, an ultraviolet-derived inflammation inhibitory action, and an anti-bedsore action, is low-irritating, has high safety, and is useful as a cosmetic, a quasi drug, a medicinal drug, a food additive, a feed additive, an animal drug, and an aquatic animal drug.SELECTED DRAWING: NoneCOPYRIGHT: (C)2016,JPOandINPIT
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-
Paragraph 0075; 0076
(2017/02/24)
-
- Hybrid ascorbic acid derivative and method of fabricating the same
-
Disclosed are: a hybrid ascorbic acid derivative which maintains strong reducibility, is physically stable, increases biocompatibility and bioactivity, and prevents the oxidation of amino acids; and a method for preparing the same. The derivative is a hybrid ascrobic acid derivative, which is 3-(amino)-L-ascrobic acid obtained by combining a first modifier and a second modifier using bromoacetyl or bromoacetyl chloride as a mediator, the first modifier being modified by introducing a first protecting group to an amino acid, the second modifier being modified by introducing a second protecting group to an ascrobic acid.
- -
-
Paragraph 0025; 0026; 0027; 0028; 0029
(2017/06/02)
-
- Preparation method of 3-O-alkyl ascorbic acid
-
The invention discloses a preparation method of 3-O-alkyl ascorbic acid. The method is characterized in that ascorbic acid with protecting groups reacts with one of organic phosphate, sulfonic ester and organosulfate on the condition that tertiary amine exists, solvent does not need to be used for extraction after the reaction, treating is performed by directly using water, therefore, the reaction and aftertreatment time is short, the purity is high, and a large amount of dimethylsulfoxide and extraction solvent are prevented from being used. According to the preparation method of the 3-O-alkyl ascorbic acid, ethyl alcohol, methyl alcohol, isopropanol, acetonitrile and the like can be adopted as the solvent used in the reaction, the organic phosphate or the sulfonic ester or the organosulfate and the like is adopted as an alkylating reagent, water is taken as the solvent for purification and separation after etherification, therefore, the cost is significantly lowered, environmental protection is achieved, and the time is shortened.
- -
-
Paragraph 0025; 0026
(2016/10/10)
-
- Synthetic study of cnicin: Synthesis of the side chain and its esterification
-
Cnicin is a germacranolide sesquiterpene lactone that possesses potent inhibitory activity against the protozoan parasite Trypanosoma brucei, which causes human African trypanosomiasis (HAT). Although cnicin has an interesting structure and attractive biological activity, synthetic studies of cnicin have not yet been reported. This report describes the synthesis of the protected side chain carboxylic acid moiety at C8 of cnicin via two routes starting from L-ascorbic acid. In addition, esterification between the synthetic side chain and salonitenolide derivative, which can be achieved via hydrolysis of cnicin and protection of the primary alcohol, was conducted. Thus, a semi-synthesis of cnicin was achieved.
- Kurita, Manami,Tanigawa, Miho,Narita, Shuhei,Usuki, Toyonobu
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supporting information
p. 5899 - 5901
(2016/12/09)
-
- VITAMIN C PRODRUGS AND USES THEREOF
-
Described herein are vitamin C prodrugs of Formula (I), (II), or (III), and pharmaceutically acceptable salts thereof. Also provided are pharmaceutical compositions, cosmetic or personal care composition, neutraceutical composition, and medical food composition thereof. Methods of using the compounds or compositions thereof for treating diseases are also provided.
- -
-
Paragraph 000230
(2015/04/15)
-
- Conjugate of vitamin C with vitamin B3 and antioxidant comprising the same
-
The present invention relates to a vitamin C-polyethylene glycol-vitamin B3 conjugate, and an antioxidant containing same. The vitamin C-polyethylene glycol-vitamin B3 conjugate according to the present invention has improved dissolvability in organic catalysts and stability, is not toxic, and can be hydrolyzed in the body to release active vitamin C and vitamin B3, and thus can be effectively used in products such as anti-aging cosmetic compositions, pharmaceutical compositions, and functional health foods.
- -
-
Paragraph 0090-0092
(2016/12/26)
-
- Design, synthesis and biological evaluation of brain targeting l-ascorbic acid prodrugs of ibuprofen with "lock-in" function
-
A novel brain targeting l-ascorbic acid derivatives with "lock-in" function were designed and synthesized as prodrugs to achieve the effective delivery of ibuprofen to brain by glucose transporter 1 (GLUT1) and the Na+-dependent vitamin C transporter SVCT2. Ibuprofen-loaded four prodrugs were tested in the animals. Results from the in vivo distribution study after i.v. administration of these four prodrugs and naked ibuprofen indicated that four prodrugs exhibited excellent transport ability across the BBB and significantly increased the level of ibuprofen in brain. Among them, prodrugs 4 showed higher brain concentration. Both biodistribution data and pharmacokinetic parameters suggested that l-ascorbic acid thiamine disulfide delivery system was a promising carrier to enhance CNS drug's delivery ability into brain.
- Zhao, Yi,Qu, Boyi,Wu, Xueying,Li, Xiaocen,Liu, Qingqing,Jin, Xiuxiu,Guo, Li,Hai, Li,Wu, Yong
-
supporting information
p. 314 - 323
(2014/06/24)
-
- N- (6- ( (2R,3S) -3,4-DIHYDROXYBUTAN-2-YLOXY) -2- (4 - FLUOROBENZYLTHIO) PYRIMIDIN- 4 - YL) -3- METHYLAZETIDINE- 1 - SULFONAMIDE AS CHEMOKINE RECEPTOR MODULATOR
-
There is provided a compound which is (a) a pyrimidine sulfonamide of formula (I) or (b) a pharmaceutically acceptable salt thereof, crystalline forms of the compound, processes for obtaining the compound, pharmaceutical intermediates used in the manufacture of the compound, and pharmaceutical compositions containing the compound. The compound is useful in the treatment of a disease/condition in which modulation of chemokine receptor activity is beneficial.
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Page/Page column 39
(2013/03/26)
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- Stereoselective total synthesis of both (6R,9R,10S,7E)- and (6S,9R,10S,7E)-epimers of oxylipin (9R,10S,7E)-6,9,10-trihydroxyoctadec-7-enoic acid
-
An asymmetric synthesis of both the stereoisomers (2a & 2b) of the structure 2 proposed for (9R,10S,7E)-6,9,10-trihydroxyoctadec-7-enoic acid, an immunostimulant oxylipin from the n-butanol extract of the corms of Dracontium loretense, has been accomplished. The key steps involved are using Jacobsen's hydrolytic kinetic resolution (HKR), Julia-Kocienski olefination, regioselective epoxide ring opening and Wittig olefination. The configuration (9R,10S,7E)-6,9,10-trihydroxyoctadec-7-enoic acid was established as 2a from comparison of NMR data, HPLC analysis and [α]D values of naturally derived (9R,10S,7E)-6,9,10-trihydroxyoctadec-7-enoic acid, and comparison with the synthetic diastereomers 2a and 2b.
- Saikia, Bishwajit,Devi, Thongam Joymati,Barua, Nabin C.
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p. 2157 - 2166
(2013/03/14)
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- Design, synthesis and preliminary biological evaluation of brain targeting l-ascorbic acid prodrugs of ibuprofen
-
l-Ascorbic acid (AA, vitamin C) exhibits a high concentration in the brain. The transportation of AA in brain is mainly mediated by the glucose transporter 1 (GLUT1) and the Na+-dependent vitamin C transporter SVCT2. While l-ascorbic acid C6O conjugation has been investigated as a tool to enhance brain drug delivery, C5O conjugation and C5O & C6O conjugation as brain targeting tools have not been reported. In this letter, ibuprofen was linked directly to C5O, C6O and C5O & C6O positions of l-ascorbic acid with eater bonds, providing prodrug 1, 2 and 3, respectively, to improve their targeting abilities in the brain. Prodrug 1, 2 and 3 were synthesized in facile ways with good yields. And the preliminary evaluation in vivo illustrated that prodrug 2 had a better targeting ability than prodrug 1. Moreover, prodrug 3, whose C5O & C6O positions were both modified, had good targeting ability for brain which will provide an important evidence for our further study on C5O- & C6O- di-derivatives of l-ascorbic acid.
- Wu, Xue-Ying,Li, Xiao-Cen,Mi, Jie,You, Jing,Hai, Li
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p. 117 - 119
(2013/07/11)
-
- SUBSTITUTED BIARYL ALKYL AMIDES
-
Disclosed herein are substituted biaryl alkyl amide compounds, methods of synthesizing substituted biaryl alkyl amide compounds and methods of treating diseases and/or conditions with substituted biaryl alkyl amide compounds.
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-
Paragraph 0251; 0252
(2013/05/08)
-
- CRYSTALLINE FORMS OF N-[2-[[(2,3-DIFLUOROPHENYL)METHYL]THIO]-6--4-PYRIMIDINYL]-1-AZETIDINESULFONAMIDE
-
There is provided crystalline forms of N-[2-[[(2,3-difluorophenyl)methyl]thio]-6-{[(1R,2S)-2,3-dihydroxy-1-methylpropyl]oxy}-4-pyrimidinyl]1-azetidinesulfon-amide anhydrate. Such compounds/forms may be useful in the treatment of a disease/condition in which modulation of chemokine receptor activity is beneficial.
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Page/Page column 8
(2012/02/01)
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- From L-ascorbic acid to protease inhibitors: Practical synthesis of key chiral epoxide intermediates for aspartyl proteases
-
Efficient synthetic routes were developed to prepare a sizable amount (4-15 grams) of the chiral epoxides 4-6 as versatile intermediates for the synthesis of aspartyl protease inhibitors of therapeutic interest such as HIV protease and β-secretase. Oxidative cleavage of the C(2)-C(3) double bond of L-ascorbic acid followed by functional group manipulation led to the preparation of the epoxide 10, which was opened with an azide to yield a common aziridine intermediate 12. Through opening of the aziridine ring of 12 with either a carbon or a sulfur nucleophile, chiral epoxide precursors 4-6 could be prepared for various HIV protease inhibitors. Except for the final low melting epoxides 5 and 6, all intermediates were obtained as crystalline solids, thus the synthetic pathway can be easily applied to a large-scale synthesis of the chiral epoxides.
- Chang, Sun Ki,So, Soon Mog,Lee, Sang Min,Kim, Min Kyu,Seol, Kyoung Mee,Kim, Sung Min,Kang, Jae Sung,Choo, Dong Joon,Lee, Jae Yeol,Kim, B. Moon
-
experimental part
p. 2213 - 2218
(2012/09/21)
-
- Efficient asymmetric synthesis of (2R,3R)-3-{(1R)-1-[tert-Butyl(dimethyl)- siloxy]ethyl}-4-oxoazetidin-2-yl acetate
-
(2R,3R)-3-{(1R)-1-[tert-Butyl(dimethyl)siloxy]ethyl}-4-oxoazetidin-2-yl acetate was efficiently prepared from l-ascorbic acid. The key steps were the a highly diastereoselective [2 + 2] cycloaddition of diketene with an (S)-glyceraldehyde-derived ald?imine to give the ketone, stereoselective titanium tetrachloride mediated asymmetric reduction to give the corrsponding S-configured alcohol, and Mitsunobu inversion of the latter to give the desired R-configured alcohol. Georg Thieme Verlag Stuttgart ? New York.
- Huang, Jian-Ping,Zhao, Lei,Gu, Shuang-Xi,Wang, Zhong-Hua,Zhang, Hao,Chen, Fen-Er,Dai, Hui-Fang
-
experimental part
p. 555 - 562
(2011/04/15)
-
- Stereoselective synthesis of (+)-(1R,2S,5S,7R)-2-hydroxy-exo-brevicomin
-
A stereoselective approach for the synthesis of (+)-(1R,2S,5S,7R)-2- hydroxy-exo-brevicomin from l-ascorbic acid has been described. The key steps are highly stereoselective nucleophilic addition reaction on aldehyde 8 and also a single pot transformation of 15 to (+)-(1R,2S,5S,7R)-2-hydroxy-exo- brevicomin. The later tandem reaction which involves the hydrogenation of double bond, debenzylation, MOM deprotection and bicyclic ketal formation was carried under Pd/C, H2 followed by acid treatment.
- Gautam,Rao, B. Venkateswara
-
supporting information; experimental part
p. 4199 - 4201
(2010/09/12)
-
- Ascorbic Acid Derivatives
-
The present invention discloses the ascorbic acid derivatives. The inventive molecules that combine with one or two hydrophilic headgroups connected by a hydrophobic spacer can increase skin penetration.
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-
Page/Page column 3
(2010/04/23)
-
- ASCORBIC ACID DERIVATIVES, THEIR PREPARATION METHODS, INTERMEDIATES AND USES IN COSMETICS
-
A kind of ascorbic acid derivates 3-O-glyco-L-ascorbic acid, their preparation methods, intermediates and uses in cosmetics. The derivates used as vitamin C precursors have better physiological effect than 2-O-α-D-glucopyranosyl ascorbic acid (AA-2G) and are more stable. Present compounds can be used in many fields, such as in cosmetics, pharmaceuticals, foodstuffs and livestock feed, and especially as whitening agents in cosmetics. The preparation method involves protecting the 5,6-dihydroxyl of ascorbic acid, then coupling with 1-haloacylglycosyl, obtaining the intermediate 3-O-(acylglycosyl)-(5,6-O-isopropylidine)-L-ascorbic acid, removing the isopropylidine and acyl from the intermediates, thereby obtaining the target substance.
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Page/Page column 5-6
(2010/08/18)
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- Artificial transcription factors which mediate double-strand DNA Cleavage
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A new family of artificial transcription factor (ATF)-based conjugates have been designed and synthesized as potent chemical nucleases. Polyamides as the important and efficient ATFs were used to modify and activate several anchor compounds. The results demonstrate that the resulting conjugates remarkably promote the rate accelerations and non-random double-strnd DNA cleavage activity. Interestingly, the cleavage activity of both the hydrolytic and oxidative agents was promoted efficiently through the modification of the ATFs.
- Li, Chao,Du, Chao,Tian, Hua,Jiang, Chao,Du, Min,Liu, Yan,Qiao, Ren-Zhong,Jia, Yan-Xing,Zhao, Yu-Fen
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supporting information; scheme or table
p. 12935 - 12940
(2011/02/25)
-
