- Design, synthesis and evaluation of wound healing activity for β-sitosterols derivatives as potent Na+/K+-ATPase inhibitors
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β-Sitosterols, is a common steroid that can be identified in a variety of plants and their efficacy in promoting wound healing has been demonstrated. Na+/K+-ATPase, more than a pump, its signal transduction function for involvement in cell growth regulation attracts widespread concern. The Na+/K+-ATPase/Src receptor complex can serve as a receptor involved in multiple signaling pathways including promoting wound healing pathways. To finding potent accelerating wound healing small molecular, we choose the high inhibitory activity of Na+/K+-ATPase and non-cardiotoxic natural compound, β-sitosterol as the substrate. A series of β-sitosterol derivatives were designed, synthesized and evaluated as potential Na+/K+-ATPase inhibitors. Among them, compounds 31, 47, 49, showed improved inhibitory activity on Na+/K+-ATPase, with IC50 value of 3.0 μM, 3.4 μM, 2.2 μM, which are more potent than β-sitosterol with IC50 7.6 μM. Especially, compound 49 can induce cell proliferation, migration and soluble collagen production in L929 fibroblasts. Compared to model, compound 49 can accelerate wound healing in SD rats. Further studies indicated that 49 can activate the sarcoma (Src), uptake the protein kinase B (Akt), extracellular signal-regulated kinase (ERK) proteins expression in a concentration dependent manner. Finally, binding mode of compound 49 with Na+/K+-ATPase was studied, which provides insights into the determinants of potency and selectivity. These results proved β-stitosterol derivative 49 can serve as an effective inhibitor of Na+/K+-ATPase and potential candidate for accelerating wound healing agents.
- Cui, Shaoyu,Jiang, Hongli,Chen, Lei,Xu, Jian,Sun, Wenzhuo,Sun, Haopeng,Xie, Zijian,Xu, Yunhui,Yang, Fubai,Liu, Wenyuan,Feng, Feng,Qu, Wei
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- Sterol derivatives and its preparation method and application
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The invention discloses a sterol derivative of beta-sitosterol, beta-stigmasterol and cholesterol, and is shown as a formula VI. The invention also discloses a preparation method of the sterol derivative. The invention also discloses application of the sterol derivative to the aspect of preparation of wound healing promoting medicine. By starting from easily obtained natural products, the beta-sitosterol, the beta-stigmasterol and the cholesterol are used as starting raw materials; the synthetic method is simple; better operability and reaction yield are realized. The prepared sterol derivative has the obvious wound healing promoting activity; the multiplication, migration and collagen synthesis capability on L929 mechanocytes is obviously higher than that of the raw material and positive control medicine recombinant human bFGF (basic fibroblast growth factor). Compared with protide type medicine (such as bFGF), the prepared sterol derivative has more diversified dosage forms and medication modes; the reference is provided for the application in the field of wound healing promoting. The formula VI is shown as the accompanying diagram.
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Paragraph 0189-0191
(2019/05/19)
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- O - substituted hydroxylamine hydrochloride and its preparation method (by machine translation)
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The present invention provides a O - substituted hydroxylamine hydrochloride and its preparation, wherein the preparation method comprises the following steps: step S1, to the acetyl hydroximic acid ethyl ester in ethanol solution of adding sodium hydroxide, in addition at the same time instillment halohydrocarbon, chloride or acyl chloride substitution reaction to take place, then added to the water in order to separate out the O - substituted [...]; step S2, the said O - substituted [...] adding hydrochloric acid solution in order to produce reflux reaction O - substituted hydroxylamine hydrochloride. According to the embodiment of the invention of the O - substituted hydroxylamine hydrochloride of the preparation method, high purity of the product can be obtained, and the method is safe, easy to process, the process is simple, and is suitable for industrial production. (by machine translation)
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Paragraph 0065; 0068; 0069
(2018/10/11)
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- Synthetic Study on Acremoxanthone A: Construction of Bicyclo [32.2]nonane CD Skeleton and Fusion of AB Rings
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Toward the total synthesis of acremoxanthone A, a model study has revealed a convergent approach to construct the ABCDE ring system. The key steps include: (1) an effective construction of the bicyclo[3.2.2]nonane skeleton, (2) protocol for generating the bridgehead anion and trapping, and (3) 1,3-dipolar cycloaddition of a nitrile oxide to the internal alkene.
- Hirano, Yoichi,Tokudome, Kensei,Takikawa, Hiroshi,Suzuki, Keisuke
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supporting information
p. 214 - 220
(2017/01/25)
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- Industrialization method for synthesizing O-chloropropene hydroxylamine by virtue of one-pot method
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The invention discloses an industrialization method for synthesizing O-chloropropene hydroxylamine by virtue of a one-pot method and a catalyst utilized in the industrialization method. The industrialization method comprises the following steps: adding acetic ester, hydroxylammonium salt and a catalyst A into a reaction kettle, adding alkali metal hydroxide, and stirring to react at 0-50 DEG C for 0-10 hours so as to generate acetohydroxamic acid; continuing to add a catalyst B and dichloropropene into reaction liquid to generate etherification reaction at 20-80 DEG C for 0-20 hours, so as to obtain N-acetyl-O-chloropropene hydroxylamine; and continuing to add protonic acid to generate acidification at 20-100 DEG C for 0-10 hours, so as to prepare O-chloropropene hydroxylammonium salt, and finally carrying out neutralization, extraction and desolvation, so as to obtain dissociative O-chloropropene hydroxylamine. The product content is higher than 99%, and the total yield is over 90%. An intermediate can be utilized for preparing high-content cyclohexenone herbicides by virtue of further reaction, is applicable to large-scale industrial production, low in cost and high in product purity and yield, and the operation is easy.
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Paragraph 0027; 0028; 0029; 0030
(2016/12/01)
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- With biological activity mixed oxygen benzene oxygen N- the oxygen radical is thick carboxylic acid amide compound and its preparation method
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The present invention discloses a N-oxyl fused heterocycle oxy phenoxy carboxylic acid amide compound having biological activity, and a preparation method thereof, wherein the compound is represented by a formula (I), A is selected from the following groups, R is C3-C6 alkenyl, C3-C6 alkynyl, C3-C6 halogenated alkenyl, C3-C6 halogenated alkynyl, C3-C6 cycloalkyl methyl and C3-C6 halogenated cycloalkyl alkyl methyl, R1 is H, C1-C3 alkyl, and C1-C3 halogenated alkyl, and R2 is H, halogen, C1-C3 alkyl, and C1-C3 halogenated alkyl. The compound represented by the formula (I) has broad-spectrum biological activity of weed removing or insect killing and bacterial killing, wherein some compounds have high weed removing activity and can achieve a good prevention and control effect at a use amount of 3.75-75 g effective component/hectare.
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Paragraph 0074; 0093; 0094; 0095
(2016/10/08)
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- Aldol Condensations Catalyzed by Basic Anion-Exchange Resins
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The aldol condensations of various aldehydes with ketones in the presence of anionic (basic) ion-exchange resins have been investigated. Both batch and continuous modes were studied and compared for the reaction of citral (a mixture of geranial and neral) with acetone to give ψ-ionone. Different reaction conditions were investigated, and the performances of five different ion-exchange resins were compared. The most stable resins could be used for 10 cycles in batch mode or 1000 min in continuous mode without a significant loss in activity or selectivity.
- Bonrath, Werner,Pressel, Yann,Schütz, Jan,Ferfecki, Erich,Topp, Klaus-Dieter
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p. 3584 - 3591
(2016/12/14)
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- NOVEL VASCULAR LEAKAGEAGE INHIBITOR
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The present disclosure relates to a novel vascular leakage inhibitor. The novel vascular leakage inhibitor of the present invention inhibits the apoptosis of vascular endothelial cells, inhibits the formation of actin stress fibers induced by VEGF, and enhances the cortical actin ring structure, thereby inhibiting vascular leakage. Accordingly, the vascular leakage inhibitor of the present invention can prevent or treat various diseases caused by vascular leakage. Since the vascular leakage inhibitor of the present invention is synthesized from commercially available or easily synthesizable pregnenolones, it has remarkably superior feasibility of commercial synthesis.
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Paragraph 0094
(2015/01/07)
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- Glucal-conjugated sterols as novel vascular leakage blocker: Structure-activity relationship focusing on the C17-side chain
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A series of glucal-conjugated sterols as novel vascular leakage blocker were identified through design, synthesis and biologically evaluation. In addition, the structure-activity relationship (SAR) of the glucal-conjugated sterols focusing on the C17-side chain was also established. The sterol analogs linked with the rigid C17-side chain side chains exhibited potent cell survival activities. In particular, analog 21l, which possesses a cyclopentyl oxime moiety, was shown to have excellent pharmacological effects on retinal vascular leakage in a diabetic mouse model.
- Kim, Kyeojin,Maharjan, Sony,Lim, Changjin,Kim, Nam-Jung,Agrawal, Vijayendra,Han, Young Taek,Lee, Sujin,An, Hongchan,Yun, Hwayoung,Choi, Hyun-Jung,Kwon, Young-Guen,Suh, Young-Ger
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p. 184 - 194
(2014/03/21)
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- Rapid synthesis of alkoxyamine hydrochloride derivatives from alkyl bromide and N,N′-Di-tert-butoxycarbonylhydroxylamine [(Boc)2NOH]
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The conventional route to alkoxyamine hydrochloride derivatives is by reaction of alkyl bromides with N-hydroxyphthalimide or N-hydroxysuccinimide followed by addition of hydrazine and HCl. Transformation of an alkyl bromide to the corresponding alkoxyamine hydrochloride can be accomplished more rapidly in good yields without using hazardous hydrazine by reaction of (Boc) 2NOH (N,N′-di-tert-butoxycarbonylhydroxylamine) and alkyl bromide followed by addition of HCl. Alkoxyamine hydrochlorides are powerful reagents in organic synthesis that can be used to synthesize alkoxyimino derivatives after condensation with a ketone or aldehyde. Copyright
- Jayasekara, P. Suresh,Jacobson, Kenneth A.
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supporting information
p. 2344 - 2347
(2014/07/22)
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- New and concise syntheses of the bicyclic oxamazin core using an intramolecular nitroso diels-alder reaction and ring-closing olefin metathesis
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Herein two new and concise synthetic approaches for making an unsaturated bicyclic oxamazin core are reported. The first involves the use of an intramolecular Diels-Alder reaction to form both of the fused rings in one step. The second approach incorporates ring-closing olefin metathesis in the final step to form the second fused ring of the core. The scope of the second approach was also expanded further to afford larger ringed bicyclic systems.
- Watson, Kyle D.,Carosso, Serena,Miller, Marvin J.
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p. 358 - 361
(2013/03/13)
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- Aldol condensation reaction and catalyst therefore
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The invention relates to a novel processes for cross aldol reactions using strongly basic, anionic, macroreticular polymeric resin with quaternary ammonium groups of the type -CH2N+(CH3)3 as heterogeneous catalysts. This catalyst is recyclable and the process can be repeated several times.
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Page/Page column 7
(2009/01/20)
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- NOVEL PROCESS FOR THE PREPARATION OF TIMBERONE
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This invention relates to a novel process for the preparation of timberone useful for perfume or cosmetics.
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Page/Page column 2; 6-7
(2008/12/07)
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- ALDOL CONDENSATION
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The invention relates to a novel processes for producing ketones, and more specifically, to processes for producing unsaturated ketones using Ca/Na on silica as solid base supported catalysts. This process results in yields and greater selectivity for the target products, while allowing the recycling of the catalyst.
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Page/Page column 5; 8
(2008/12/07)
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- Synthesis and fungicidal activity of macrolactams and macrolactones with an oxime ether side chain
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Three series of novel macrolactams and macrolactones - 12-alkoxyimino- tetradecanlactam, 12-alkoxyiminopentadecanlactam, and 12-alkoxyiminodecanlactone derivatives (7A, 7B, and 7C) - were synthesized from corresponding 12-oxomacrolactams and 12-oxomacrolactone. Their structures were confirmed by 1H NMR and elemental analysis. The Z and E isomers of 7A and 7B were separated, and their configurations were determined by 1H NMR. These compounds showed fair to excellent fungicidal activities against Rhizoctonia solani Kuehn. It is interesting that the Z and E isomers of most of the compounds have quite different fungicidal activities. The fact that the compounds have a gradual increase of fungicidal activity in the order of 7A, 7C, and 7B indicated that the macrocyclic derivatives with a hydrogen-bonding acceptor (=N-O-) and a hydrogen-bonding donor (-CONH-) on the ring, and a three methylenes distance (CH2CH2CH2) between these two functional groups, exhibited the best fungicidal activity. The bioassay also showed that 7B not only has good fungicidal activity but also may have a broad spectrum of fungicidal activities.
- Huang, Jia-Xing,Jia, Yue-Mei,Liang, Xiao-Mei,Zhu, Wei-Juan,Zhang, Jian-Jun,Dong, Yan-Hong,Yuan, Hui-Zu,Qi, Shu-Hua,Wu, Jin-Ping,Chen, Fu-Heng,Wang, Dao-Quan
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experimental part
p. 10857 - 10863
(2009/11/30)
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- Quinoline synthesis: Scope and regiochemistry of photocyclisation of substituted benzylidenecyclopentanone O-alkyl and O-acetyloximes
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Irradiation of substituted 2-benzylidenecyclopentanone O-alkyl and O-acetyloximes in methanol provides a convenient synthesis of alkyl, alkoxy, hydroxy, acetoxy, amino, dimethylamino and benzo substituted annulated quinolines. para-Substituents yield 6-substituted-2,3-dihydro-1H-cyclopenta[b] quinolines with 8-substituted products being obtained from ortho-substituted starting materials. Reactions of meta-substituted precursors are highly regioselective, with alkyl substituents leading to 5-substituted 2,3-dihydro-1H-cyclopenta[b]quinolines and more strongly electron-donating substituents generally resulting in 7-substituted products. 2-Furylmethylene and 2-thienylmethylene analogues yield annulated furo- and thieno-[2,3e]pyridines respectively. Sequential E- to Z-benzylidene group isomerisation and six π-electron cyclisation steps result in formation of a short-lived dihydroquinoline intermediate which spontaneously aromatises by elimination of an alcohol or acetic acid. For 2-benzylidenecyclopentanone O-allyloxime, singlet excited states are involved in both steps. The Royal Society of Chemistry 2007.
- Austin, Mark,Egan, Oliver J.,Tully, Raymond,Pratt, Albert C.
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p. 3778 - 3786
(2008/10/09)
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- Intermolecular electrophilic O-amination of alcohols
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We report the first examples of an intermolecular electrophilic O-amination of aliphatic alcohols. Thus, the new reagents, fluorenone oxime tosylate, 5a, or mesylate, 5b, permit O-amination of diverse alcohols in the presence of NaH under mild conditions. By following the formation of the resulting oxime ethers, 6, the reaction was shown to be sensitive to steric effects in the alcohol. Furthermore, the presence of an aromatic ring or of a double bond in the alcohol molecule (benzyl, allyl) was found to increase the reaction rate.
- Hassner, Alfred,Patchornik, Guy,Pradhan, Tarun K.,Kumareswaran
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p. 658 - 661
(2007/10/03)
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- Synthesis and stereoisomerization of 2-(1-alkoxyimino-2,2,2-trifluoroethyl) -5-trimethylsilylfurans
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2-(1-Alkoxyimino-2,2,2-trifluoroethyl)-5-trimethylsilylfurans were synthesized by the condensation of 2-(trifluoroacetyl)-5-trimethylsilylfuran with alkoxyamines. According to 1H and 19F NMR spectroscopic data, the alkoxyimino group in the E-isomers descreens the H-3 and H-4 protons of the furan ring more strongly than in the Z-isomers, shifting their signals downfield. The fluorine atoms of the α-trifluoromethyl group in the Z-isomer are characterized by a downfield shift in relation to the E-isomer. 2005 Springer Science+Business Media, Inc.
- Melnik,Vorona,Veinberg,Popelis,Ignatovich,Lukevics
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p. 718 - 721
(2007/10/03)
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- Probing the 'active site' of diamine oxidase: Structure-activity relations for histamine potentiation by O-alkylhydroxylamines on colonic epithelium
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The responses of the canine colonic epithelium to histamine are potentiated by O-alkylhydroxylamines. A study of a series of such compounds suggested that active compounds had the structure R-O-NH2, substitution of a nitrogen led to total loss of activity. The locus of the potentiation effect was traced to the inhibition of diamine oxidase. A new series of aliphatic and aromatic O-alkylhydroxylamines were synthesized to explore further the structure-activity relations of this effect. The potentiating effects of these compounds were determined by examining the changes in short circuit current (I(sc)) produced by histamine and from the activity of a soluble preparation of diamine oxidase. We found that 1) branched compounds are less active than their straight chain counterparts, 2) greater steric bulk of the aliphatic substituent decreased activity, 3) the presence of a double bond had no significant effect though a triple bond reduced activity, 4) longer straight chain compounds were less active than the shorter chain derivatives and 5) all benzylic compounds were less active than the straight chain aliphatics. O-1-benzyl was inactive however the meta or para oxygen substituted compounds as well as the O-(1-E-Cinnamyl) derivative were active. A current model for the action of diamine oxidase proposes a crucial role for a trihydroxyphenylalanine quinone cofactor as part of the active site together with a copper atom. Using molecular modeling based on our inhibition data we are able to define the region of space that is just beyond the reactive carbonyl of the trihydroxyphenylalanine residue at the active site of diamine oxidase. We suggest that a negatively charged species, such as an aspartate or a glutamate, resides in a trough about 7 to 8 A from the trihydroxyphenylalanine carbonyl carbon and this species aids in the strong selective binding of substrates such as putrescine and histamine.
- High,Prior,Bell,Rangachari
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p. 490 - 501
(2007/10/03)
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- Symmetrical O-substituted dioximes of benzo-fused β-diketocyclo-alkylenes, the processes for their preparation and their application as drugs
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Drugs with high anticonvulsant and analgesic activities constituted by symmetrical β-dialkoxyiminocycloalklene derivatives in which the imine double bonds are conjugated with the cyclic double bond or bonds belonging to one or more fused benzene rings. They correspond to the general formula I: STR1
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- Reactions of N-Acyl-O-arylhydroxylamines: Part IV - Preparation of Some N-Arylsulphonyl-O-arylhydroxylamines
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A number of N-arylsulphonyl-O-alkylhydroxylamines (III) have been prepared by condensing appropriate alkoxyamines with arylsulphonyl chlorides in the presence of a base.The alkoxyamines have been obtained from the corresponding alkoxyamine hydrochlorides or hydrobromides (II) which in turn have been prepared by the hydrolysis of appropriate N-benzoyl-O-alkylhydroxylamines (I) with ethanolic hydrogen chloride or hydrogen bromide.The structure assignments of III are based on elemental analyses, chemical reaction and spectral (IR, PMR) data.
- Singha, A. S.,Misra, B. N.
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p. 361 - 363
(2007/10/02)
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- 1-Azaxanthone-3-carboxylic acids and their production
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Novel 1-azaxanthone-3-carboxylic acid derivatives, which are shown by the following formula (I) STR1 wherein R is hydrogen, alkyl, alkoxy or halogen; R1 and R2 are the same or different and each is hydrogen, alkyl or alkenyl; and m is 1 or 2; and their physiologically acceptable salts, are usable as effective medicines for preventing and/or treating allergic diseases. The compound of the formula (I) can be produced by reacting a compound of the formula: STR2 wherein R and m have the same meaning as defined above; R3 is carboxyl or group which is convertible into carboxyl through hydrolysis; X is alkyl phosphate radical or halogen, with a compound of the formula: STR3 wherein R1 and R2 have the same meaning as defined above, or its salt, and conducting hydrolysis, if necessary.
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