- Design, Synthesis, and Biological Evaluations of Several Y-26732 Analogues
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A series of pyridine Rho kinase inhibitors were designed and synthesized utilizing the ligand-binding pocket model with Y-26732 as the lead compound. These compounds were evaluated on cell lines for their biological activities.
- Wang, Xinran,Chen, Ligong,Li, Hang,Sun, Changhai,Qi, Haofei,Wang, Donghua
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- Direct evidence of significantly different chemical behavior and excited-state dynamics of 1,7- and 1,6-regioisomers of pyrrolidinyl-substituted perylene diimide
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Novel bay-functionalized perylene diimides with additional substitution sites close to the perylene core have been prepared by the reaction between 1,7(6)-dibromoperylene diimide 6 (dibromo-PDI) and 2-(benzyloxymethyl) pyrrolidine 5. Distinct differences in the chemical behaviors of the 1,7- and 1,6-regioisomers have been discerned. While the 1,6-dibromo-PDI produced the corresponding 1,6-bis-substituted derivative more efficiently, the 1,7-dibromo-PDI underwent predominant mono-debromination, yielding a mono-substituted PDI along with a small amount of the corresponding 1,7-bis-substituted compound. By varying the reaction conditions, a controlled stepwise bis-substitution of the bromo substituents was also achieved, allowing the direct synthesis of asymmetrical 1,6- and 1,7-PDIs. The compounds were isolated as individual regioisomers. Fullerene (C60) was then covalently linked at the bay region of the newly prepared PDIs. In this way, two separate sets of perylene diimide-fullerene dyads, namely single-bridged (SB-1,7-PDI-C60 and SB-1,6-PDI-C60) and double-bridged (DB-1,7-PDI-C60 and DB-1,6-PDI-C60), were synthesized. The fullerene was intentionally attached at the bay region of the PDI to achieve close proximity of the two chromophores and to ensure an efficient photoinduced electron transfer. A detailed study of the photodynamics has revealed that photoinduced electron transfer from the perylene diimide chromophore to the fullerene occurs in all four dyads in polar benzonitrile, and also occurs in the single-bridged dyads in nonpolar toluene. The process was found to be substantially faster and more efficient in the dyads containing the 1,7-regioisomer, both for the singly- and double-bridged molecules. In the case of the single-bridged dyads, SB-1,7-PDI-C60 and SB-1,6-PDI-C60, different relaxation pathways of their charge-separated states have been discovered. To the best of our knowledge, this is the first observation of photoinduced electron transfer in PDI-C60 dyads in a nonpolar medium. Copyright
- Dubey, Rajeev K.,Niemi, Marja,Kaunisto, Kimmo,Efimov, Alexander,Tkachenko, Nikolai V.,Lemmetyinen, Helge
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- Design, synthesis and evaluation of novel 2-hydroxypyrrolobenzodiazepine-5, 11-dione analogues as potent angiotensin converting enzyme (ACE) inhibitors
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Under the guidance of combination of traditional Chinese medicine chemistry (CTCMC), this study describes the preparation of a phenolic acid/dipeptide/borneol hybrid consisting of phenolic acid and a bornyl moiety connected to the dipeptide N-terminal and C-terminal respectively. It also evaluates their angiotensin converting enzyme (ACE) inhibitory and synergistic antihypertensive activities. Briefly, a series of novel 2-hydroxypyrrolobenzodiazepine-5, 11-dione analogues were prepared and investigated for their ability to inhibit ACE. The influence of the phenolic acid and bornyl moiety on subsite selectivity is also demonstrated. Among all the new compounds, two compounds-7a and 7g-reveal good inhibition potency in in vitro ACE-inhibitory tests. Interestingly, favorable binding results in molecular docking studies also supported the in vitro results. Additionally, the bioassay showed that oral administration of the two compounds displayed high and long-lasting antihypertensive activity both in acute antihypertensive tests and in therapeutic antihypertensive tests by non-invasive blood pressure measurements in spontaneously hypertensive rats.
- Sun, Ying,Bai, Yujun,He, Xirui,Bai, Yajun,Liu, Pei,Zhao, Zefeng,Chen, Xufei,Zheng, Xiaohui
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- Contiguous generation of quaternary and tertiary stereocenters: One-pot synthesis of chroman-fused S-proline-derived chiral oxazepinones
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A new class of chroman-fused S-proline-derived chiral oxazepinones has been synthesized in one pot through contiguous generation of quaternary and tertiary stereocenters.
- Singh, Ritesh,Parai, Maloy Kumar,Mondal, Sankalan,Panda, Gautam
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- Intramolecular Alkylation of Carboxylic Acids: Application to the Synthesis of Boc-Protected Cyclic Amino Acids
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A new synthesis of Boc-protected cyclic amino acids is described as an application of an unreported method of lithium diisopropylamide-induced cyclisation of ω-chloro carboxylic acids containing a protected amine function in the chain.
- Nicola, A. De,Einhorn, C.,Einhorn, J.,Luche, J. L.
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- Synthesis of alexine-like compounds from chiral five-membered endocyclic enecarbamates
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Stereoselective syntheses of enantiomerically enriched trihydroxy pyrrolizidine and indolizidines were accomplished from a common chiral endocyclic enecarbamate. The synthetic strategy features an efficient [2+2] cycloaddition of ketenes to the endocyclic enecarbamate and a highly regioselective Baeyer-Villiger oxidation of the intermediate azabicyclic-cyclobutanones. These new heterocycles are compounds structurally related to the alexines.
- Valle, Marcelo Siqueira,Retailleau, Pascal,Correia, Carlos Roque Duarte
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- Hydrolysis of Pro-Ala Dipeptides by Lysosomal Hydrolases. Models for the Study of Lysosomotropic Amino Acid Prodrugs of Penicillins
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Peptidic lysosomotropic prodrugs of antibiotics and antitumoral agents could be of advantage in chemotherapy, providing that free, active drug is released at, or close to, the desired site of action.Thus, aminoacyl derivatives of doxorubicin, e.g., where the drug is attached to the amino acid by a primary amino function, are sensitive to lysosomal hydrolases.We have examined whether a similar approach can be used for drugs carrying a carboxyl group such as β-lactam antibiotics.Because the C adjacent to the carboxyl group in β-lactams has the D configuration, we have examined and report here the synthesis and susceptibility of model peptides, namely Boc-D-Pro-L-Ala and Boc-L-Pro-L-Ala to lysosomal hydrolases.Hydrolysis of the D isomer proceeds considerably more slowly than that of the L isomer.Lysosomal carboxypeptidase(s) and/or amidases appear therefore to have a much narrower specificity than aminopeptidase(s), which will severely limit the applicability of the concept of peptidic lysosomotropic prodrugs.
- Renard, C,Michel, A.,Tulkens, P. M.
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- Synthesis and biological evaluation of pyrrolidine-2-carbonitrile and 4-fluoropyrrolidine-2-carbonitrile derivatives as dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes
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A novel series of pyrrolidine-2-carbonitrile and 4-fluoropyrrolidine-2- carbonitrile derivatives was designed, synthesized, and found to act as dipeptidyl peptidase-4 (DPP-4) inhibitors. From this series of compounds, compound 17a was identified as an efficacious, safe, and selective inhibitor of DPP-4. In vivo studies in ICR and KKAy mice showed that administration of this compound resulted in decreased blood glucose in these mice after an oral glucose challenge. Compound 17a showed high DPP-4 inhibitory activity (IC50 = 0.017 μM), moderate selectivity against DPP-4 (selective ratio: DPP-8/DPP-4 = 1324; DPP-9/DPP-4 = 1164), and good efficacy in oral glucose tolerance tests in ICR and KKAy mice. These in vivo anti-diabetic properties and its desirable pharmacokinetic profile in Sprague-Dawley rats demonstrate that compound 17a is a promising candidate for development as an anti-diabetic agent.
- Wang, Jiang,Feng, Ying,Ji, Xun,Deng, Guanghui,Leng, Ying,Liu, Hong
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- Enantioselective synthesis of (R)-homoboroproline from (S)-proline using a borylation approach
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(S)-Proline was converted through a five-step sequence into (R)-homoboroproline hydrochloride in 29% overall yield with 97% The key step was the conversion of N-Boc iodomethylpyrrolidine into the corresponding pinacol boronate ester by an efficient copper(I)-catalyzed borylation reaction by using bispinacolatodiboron.
- Georgiou, Irene,Whiting, Andrew
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Read Online
- Formal Fluorinative Ring Opening of 2-Benzoylpyrrolidines Utilizing [1,2]-Phospha-Brook Rearrangement for Synthesis of 2-Aryl-3-fluoropiperidines
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A ring expansion of 2-benzoylpyrrolidines, which involves the formal fluorinative ring opening utilizing the [1,2]-phospha-Brook rearrangement under Br?nsted base catalysis and a subsequent intramolecular reductive amination, was developed. The operationally simple three-step protocol provides an efficient access to 2-aryl-3-fluoropiperidines. The methodology was further applied to the syntheses of azepanes and tetrahydroquinolines.
- Kondoh, Azusa,Ojima, Rihaku,Terada, Masahiro
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supporting information
p. 7894 - 7899
(2021/10/20)
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- Recyclable Helical Poly(phenyl isocyanide)-Supported l-Proline Catalyst for Direct Asymmetric Aldol Reaction in Brine
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Abstract: A novel helical poly(phenyl isocyanide) bearing Boc protected l-proline pendants (poly-1m) was designed and synthesized. Removed the protecting Boc groups on the l-proline pendants led to the formation of helical polymer poly-2m, which showed high optical activity owing to the preferred right-handed helix of polyisocyanide main chain. Optically active helical poly-2m showed excellent catalytic ability on asymmetric aldol reaction. Helical polymer catalysts exhibited enhanced stereoselectivity in aldol reaction compared to small molecule l-proline. Under the optimized aldol reaction condition, the enantiomeric excess (ee) and diastereomeric ratio (dr) values of the aldol reaction product were respectively up to 90% and > 20/1. Moreover, the helical polyisocyanide catalyst Poly-2m can be easily recovered and reused in the aldol reaction for at least five cycles with maintained its activity and stereoselectivity. Graphic Abstract: Enantioselective aldol reaction catalyzed by poly-2m.[Figure not available: see fulltext.]
- Li, Chonglong,Wang, Jihai,Ding, Huiyun
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p. 1180 - 1190
(2020/09/07)
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- Leonurine derivative and application thereof in preparing medicine for preventing or treating ischemic cerebrovascular diseases
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The invention provides a leonurine derivative and application of the leonurine derivative in preparation of a medicine for preventing or treating ischemic cerebrovascular diseases. The leonurine derivative has a structure as shown in a general formula (I), wherein X is selected from O or NH; Y is selected from any one of natural amino acid, substituted amino acid or amino alcohol; Z is selected from H, proline and any substituted proline. Pharmacological experiments prove that the leonurine derivative provided by the invention has the effects of neuroprotection, cerebral infarction area reduction and animal neurobehavioral scoring, and is good in safety, so that the leonurine derivative has important significance for developing novel medicines for preventing or treating ischemic cerebrovascular diseases.
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Paragraph 0110-0112
(2021/03/30)
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- A Bifunctional B,N-Based Asymmetric Catalytic Nitrostyrene-Michael Addition Acting through a 10-Membered Ring Cyclic Transition State
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The B,N-bifunctional catalyst homoboroproline has been applied to a catalytic asymmetric nitroalkene-Michael addition to β-nitrostyrene analogues, showing broad substrate tolerance, high conversions and moderate to good asymmetric induction. The ability o
- Du, Yihao,Erdem, Safiye S.,Sari, Ozlem,Whiting, Andrew
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- STABLE HEAVY ISOTOPES IN AMIDE FUNCTIONAL GROUPS AND USES THEREOF
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There are provided isotope-enriched compounds containing stable heavy isotope-enriched amide functional groups for modulating the pharmacokinetic profile, metabolic profile, and/or delivery efficiency of a drug or prodrug, as well as its therapeutic or prophylactic efficacy and/or adverse effects. Use of the isotope-enriched amide-containing drugs and prodrugs for the treatment or prevention of disease states and conditions is also provided. (I)
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Paragraph 00222
(2021/10/02)
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- Design and preparation of a novel prolinamide-based organocatalyst for the solvent-free asymmetric aldol reaction
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The preparation of four novel organocatalysts as highly diastereo and enantioselective catalysts for the solvent-free asymmetric aldol reaction was described. These organocatalysts were synthesized in eight steps applying simple and commercially available starting materials. The best results were obtained for the proline-derived catalyst, providing access to the desired adducts in up to 95% yield, 1:19 syn/anti and 98% e.e. Moreover, even sterically bulky aldehydes and substituted cyclohexanones were well tolerated. DFT calculations and control experiments indicated that several hydrogen bonding interactions between the aldehyde and the enamine intermediate are responsible for the stereoselective chiral induction process and that the trifluoroacetate counter-anion is crucial for the attainment of higher stereoselectivities.
- Martins, Rafaela de S.,Pereira, Mathias P.,de Castro, Pedro P.,Bombonato, Fernanda I.
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- Composition for promoting differentiation of skin keratinocyte comprising a SAC derivatives or a SMC derivatives
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The present invention relates to a composition for promoting keratinocyte differentiation. More specifically, SAC derivative or SMC derivatives as an active ingredient promotes differentiation of keratinocytes to promote skin keratinocyte differentiation, has excellent anti-wrinkling effect, skin barrier recovery effect, and is applicable to pharmaceutical, cosmetic, soap, body, shampoo and pack.
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Paragraph 0086-0089; 0099-0101; 0111-0114; 0124-0126
(2021/02/02)
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- Design, synthesis, and biological evaluation of novel stachydrine derivatives as potent neuroprotective agents for cerebral ischemic stroke
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Stachydrine is a natural product with multiple protective biological activities, including those involved in preventing cancer, ischemia, and cardiovascular disease. However, its use has been limited by low bioavailability and unsatisfactory efficacy. To address this problem, a series of stachydrine derivatives (A1/A2/A3/A4/B1/B2/B3/B4) were designed and synthesized, and biological studies were carried out in vitro and in vivo. When compared with stachydrine, Compound B1 exhibited better neuroprotective effects in vitro, and significantly reduced infarction size in the model of the middle cerebral artery occlusion rat model. Therefore, Compound B1 was selected for further research on ischemic stroke. [Figure not available: see fulltext.].
- Zhang, Liang,Li, Feng,Hou, Chenhui,Zhu, Sifeng,Zhong, Lili,Zhao, Jianchun,Song, Cai,Li, Wenbao
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p. 2529 - 2542
(2020/05/25)
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- Compound containing amide functional group of stable heavy isotope and application thereof
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The invention provides a compound containing a stable heavy isotope-enriched amide functional group. The compound is as shown in a formula (I) and is used for adjusting the pharmacokinetic characteristics, metabolic characteristics and/or delivery efficiency and treatment and prevention effects of a drug or a prodrug. The invention also relates to the application of the drug or prodrug containingisotope-enriched amide in the treatment or prevention of illness and symptoms of diseases.
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Paragraph 0150-0151
(2020/12/09)
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- A Facile Approach to the Synthesis of Benzothiazoles from N-Protected Amino Acids
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Abstract: –A simple trituration method for the synthesis of 2-substituted benzothiazoles derived from N-protected amino acids and 2-aminothiophenol using molecular iodine as a mild Lewis acid catalyst has been proposed. The reaction occurs in one step for 20–25 min in solve-free conditions and provides the target products in excellent yields.
- Arfan, M.,Fatima, T.,Mannan, A.,Tahira, A.
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p. 292 - 297
(2020/04/21)
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- Amide compounds, preparation method and application thereof
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The invention relates to amide compounds shown in formula I, stereoisomers or pharmaceutically acceptable salts thereof. The amide compounds and the stereoisomers or pharmaceutically acceptable saltsthereof according to the invention can inhibit the gener
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Paragraph 0040-0045
(2019/09/14)
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- Highly Diastereoselective Synthesis of Cyclic α-Aminophosphonic and α-Aminophosphinic Acids from Glycyl-l-Proline 2,5-Diketopiperazine
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This paper describes the first diastereoselective synthesis of cyclic α-aminophosphonic and α-amino phosphonic acids from glycyl-l-proline 2,5-diketopiperazine (S)-6 prepared according to the usual peptide coupling procedures. The highlights of this contribution is the chemoselective reduction of the carbamate-imide activated carbonyl group in the N-Boc 2,5-diketopiperazine (S)-11 to generate the unstable hemiaminals (1R,8aS)-12 and (1S,8aS)-13, followed by the highly diastereoselective nucleophilic addition of trimethyl phosphite or dimethyl phenylphosphonite to the chiral carbenium ion (S)-5. Acid hydrolysis of the phosphonate and phosphinate functionalities with simultaneous cleavage of the tert-butyl carbamate protecting group led to the target compounds. The high diastereoselectivity in the nucleophilic addition of trivalent phosphorus to the chiral carbenium ion (S)-5 is in agreement with our precedent reports.
- Ordó?ez, Mario,Torres-Hernández, Fernando,Viveros-Ceballos, José Luis
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p. 7378 - 7383
(2019/11/26)
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- Synthesis of a new chiral organocatalyst derived from (S)-proline containing a 1,2,4-triazolyl moiety and its application in the asymmetric aldol reaction. Importance of one molecule of water generated in situ
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A simple and efficient preparation of a novel chiral derivative of (S)-proline containing a 1,2,4-triazolyl moiety is described. The high-yielding synthetic protocol includes the use of microwave irradiation to afford new chiral pyrrolidine derivatives in
- Sánchez-Antonio, Omar,Juaristi, Eusebio
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- Efficient Analysis of 2-Acetyl-1-pyrroline in Foods Using a Novel Derivatization Strategy and LC-MS/MS
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2-Acetyl-1-pyrroline (2-AP) is a key odorant in many foods, such as aromatic rice and wheat bread, with a very low odor threshold of 0.05 μg/L in water. The small molecule with a popcornlike, roasty odor is generated biologically or by Strecker degradation within the Maillard-reaction cascades during thermal food processing with methylglyoxal and 1-pyrroline as the main direct precursors. Numerous gas-chromatographic methods for the analysis of 2-AP have been published, but the reactivity of the compound leads to discrimination or degradation during sample workup. We developed a novel derivatization method for 2-AP with o-phenylenediamine followed by HPLC-MS/MS analysis of the resulting stable quinoxaline. The precision (7%), repeatability (14%), recovery (92%), linearity (0.79-500 μg/kg), limit of detection (LOD, 0.26 μg/kg), and limit of quantitation (LOQ, 0.79 μg/kg) were validated for rice matrix and were excellent as compared with those of methods published before. With the novel method, 2-AP levels in typical foods like aromatic rice (131 μg/kg), wheat bread (18 μg/kg), brown bread (18 μg/kg), rye bread (18 μg/kg), and popcorn (38 μg/kg) were determined.
- Jost, Tobias,Heymann, Thomas,Glomb, Marcus A.
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p. 3046 - 3054
(2019/03/11)
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- Ni-Catalyzed β-Alkylation of Cyclopropanol-Derived Homoenolates
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Metal homoenolates are valuable synthetic intermediates which provide access to β-functionalized ketones. In this report, we disclose a Ni-catalyzed β-alkylation reaction of cyclopropanol-derived homoenolates using redox-active N-hydroxyphthalimide (NHPI) esters as the alkylating reagents. The reaction is compatible with 1°, 2°, and 3° NHPI esters. Mechanistic studies imply radical activation of the NHPI ester and 2e β-carbon elimination occurring on the cyclopropanol.
- Mills, L. Reginald,Zhou, Cuihan,Fung, Emily,Rousseaux, Sophie A. L.
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supporting information
p. 8805 - 8809
(2019/11/03)
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- Fluorescent nitric oxide donor for the detection and killing of: Pseudomonas aeruginosa
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The epidemic of multidrug-resistant bacteria calls for the improvement of both detection methods for bacterial infections and methods of treatment. Nitric oxide is a known potent antibacterial agent, but due to its gaseous and highly reactive nature, it is difficult to incorporate into a stable antibacterial compound. In this paper, we synthesize a nitric oxide donor attached to a fluorescent compound, creating a material that can both detect and kill the deadly multi-drug resistant bacteria strain Pseudomonas aeruginosa. Detection occurs through a bacterial enzyme-activated color change, showing a clear and obvious change from blue to yellow under UV light. The synthesized compound spontaneously releases 853 μmol of nitric oxide/g from a 10 mM initial concentration. Antibacterial efficacy studies after exposing Pseudomonas aeruginosa to a 10 mM dose of the synthesized compound show a 55-75% reduction in bacteria after 24 hours. This work is the first instance of a small molecule dual-function material that can both detect and kill bacteria.
- Hibbard, Hailey A. J.,Reynolds, Melissa M.
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supporting information
p. 2009 - 2018
(2019/03/26)
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- N-(3-(2-(4-CHLOROPHENOXY)ACETAMIDO)BICYCLO[1.1.1]PENTAN-1-YL)-2-CYCLOBUTANE-1-CARBOXAMIDE DERIVATIVES AND RELATED COMPOUNDS AS ATF4 INHIBITORS FOR TREATING CANCER AND OTHER DISEASES
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The invention is directed to substituted bridged cycloalkane derivatives. Specifically, the invention is directed to compounds according to Formula (I) wherein X, a, b, C, D, L2,L3, Y1, Y2, R2, R4, R5, R6, z2, z4, z5, and z6 are as defined herein, and salts thereof. The invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to compounds for use in methods of inhibiting the ATF4 (activating transcription factor 4) pathway and treatment of disorders associated therewith, such as e.g. cancer, neurodegenerative diseases and many other diseases, using a compound of the invention or a pharmaceutical composition comprising a compound of the invention. Preferred compounds of the invention are N-(3-(2-(4-chlorophenoxy) acetamido)bicyclo[1.1.1]pentan-l-yl)-2-cyclobutane-l-carboxamide derivatives and related compounds.
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Page/Page column 117
(2019/01/21)
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- OXADIAZOLE COMPOUNDS
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Provided herein are compounds and pharmaceutical compositions comprising said compounds that are useful for treating cancers. Specific cancers include those that are mediated by YAP/TAZ or those that are modulated by the interaction between YAP/TAZ and TEAD.
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Paragraph 00531
(2019/12/04)
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- Enantioselective Synthesis of 2,2,3-Trisubstituted Indolines via Bimetallic Relay Catalysis of α-Diazoketones with Enones
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An efficient asymmetric intramolecular trapping of ammonium ylides of α-diazoketones with enones to synthesize indoline derivatives was realized. A Rh(II)/chiral N,N′-dioxide-Sc(III) complex bimetallic relay catalytic system was established. A series of optically active 2,2,3-trisubstituted indolines were obtained in high yields (up to 99%), good enantioselectivities (up to 99% ee), and excellent diastereoselectivities (up to >19:1 dr) under mild reaction conditions.
- Yang, Jian,Ke, Chaoqi,Zhang, Dong,Liu, Xiaohua,Feng, Xiaoming
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supporting information
p. 4536 - 4539
(2018/08/07)
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- Total Synthesis of Mycenarubin A, Sanguinolentaquinone and Mycenaflavin B and their Cytotoxic Activities
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Here we report the first total synthesis of the fungal alkaloids mycenarubin A, sanguinolentaquinone and mycenaflavin B. The pyrroloquinoline alkaloid mycenarubin A was obtained in 10 steps (21 % total yield, 92 % ee) from the known key precursor 6,7-bis(benzyloxy)indole by an asymmetric alkylation and a biomimetic ring closure as the key steps. The indolo-6,7-quinone sanguinolentaquinone was obtained in eight steps (28 % total yield). Mycenaflavin B was also obtained in eight steps starting from the same key precursor (total yield 15 %) by a biomimetic ring closure and an acid-catalysed decarboxylation reaction as the key steps. The cytotoxic activities of mycenarubin A and mycenaflavin B were evaluated against mouse fibroblasts (L929) and human malignant melanoma cells (RPMI-7951).
- Backenk?hler, Jana,Reck, Bernhard,Plaumann, Markus,Spiteller, Peter
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supporting information
p. 2806 - 2816
(2018/06/04)
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- Pharmaceutical combination of an atypical antipsychotic and an NMDA modulator for the treatment of schizophrenia,bipolar disorder, cognitive impairment and major depressive disorder
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This disclosure features combinations of NMDA modulators and atypical antipsychotics. The disclosure provides for example, methods of treating schizophrenia, bipolar disorder, and/or cognitive impairment disorder in a patient in need thereof, comprising administering e.g., rapastinel and an atypical antipsychotic.
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Paragraph 0123-0125; 0151-0153
(2018/10/11)
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- Method and using tracer charged ion channel
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The invention provides compounds, compositions, methods, and kits for the treatment of pain, itch, and neurogenic inflammation.
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Paragraph 0350; 0352; 0353-0355
(2018/08/20)
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- Desyl and phenacyl as versatile, photocatalytically cleavable protecting groups: A classic approach in a different (visible) light
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A highly efficient, catalytic strategy for the deprotection of classical phenacyl (Pac) as well as desyl (Dsy) protection groups has been developed using visible light photoredox catalysis. The deliberate use of a neutral two-phase acetonitrile/water mixture with K3PO4 applying catalytic amounts of [Ru(bpy)3](PF6)2 in combination with ascorbic acid is the key to this truly catalytic deprotection of Pac- and Dsy-protected carboxylic acids. Our mild yet robust protocol allows for fast and selective liberation of the free carboxylic acids in very good to quantitative yields, while only low catalyst loadings (1 mol %) are required. Both Pac and Dsy, easily introduced from commercially available precursors, can be applied for the direct protection of carboxylic acids and amino acids, offering orthogonality to a great variety of other common protecting groups. We further demonstrate the general applicability and versatility of these formerly underrated protecting groups in combination with our catalytic cleavage conditions, as underscored by the gained high functional group tolerance. Moreover, this method could successfully be adapted to the requirements of solidphase synthesis. As a proof of principle for an efficient visible light, photocatalytic linker cleavage, a Boc-protected tripeptide was split off from commercially available brominated Wang resin.
- Speckmeier, Elisabeth,Zeitler, Kirsten
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p. 6821 - 6826
(2017/11/06)
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- Synthesis of the C(1)-C(13) Fragment of Leiodermatolide via Hydrogen-Mediated C-C Bond Formation
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The C(1)-C(13) fragment of the antimitotic marine macrolide leiodermatolide is prepared in seven steps via hydrogenative and transfer-hydrogenative reductive C-C couplings. A hydrogen-mediated reductive coupling of acetylene with a Roche-type aldehyde is used to construct C(7)-C(13). A 2-propanol-mediated reductive coupling of allyl acetate with (E)-2-methylbut-2-enal at a low loading of iridium (1 mol %) is used to construct C(1)-C(6), which is converted to an allylsilane using Oestereich's copper-catalyzed allylic substitution of Si-Zn reagents. The union of the C(1)-C(6) and C(7)-C(13) fragments is achieved via stereoselective Sakurai allylation.
- Roane, James,Wippich, Julian,Ramgren, Stephen D.,Krische, Michael J.
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supporting information
p. 6634 - 6637
(2017/12/26)
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- Imidazolidone derivative and synthesis method thereof
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The invention discloses an imidazolidone derivative and a synthesis method thereof. The name of the derivative is (5S)-3-cyclohexyl-2,4-dicarbonyl-1,3-diazabicyclo[3,3,0]octane. The synthesis method comprises the following steps: 1, synthesizing N-t-butyloxycarboryl-L-proline; 2, synthesizing N-t-butyloxycarboryl-L-prolyl-dicyclohexylurea; 3, synthesizing (5S)-3-cyclohexyl-2,4-dicarbonyl-1,3-diazabicyclo[3,3,0]octane. According to the synthesis method, the number of reaction steps is relatively small, the yield is relatively high, and the defects of a lot of reaction steps, complicated post-treatment, low yield and the like of the conventional synthesis of an imidazolidone compound are overcome; the novel imidazolidone derivative is prepared, which can meet the demand for industrial production of the imidazolidone compound.
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Paragraph 0009; 0014
(2017/10/13)
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- a-ASARY-LALDEHYDE ESTER, PREPARATION METHOD THEREFOR, AND APPLICATION THEREOF
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The present invention relates to α-asary-laldehyde ester, a preparation method therefor, and an application thereof. The chemical structure of the related α-asary-laldehyde ester is represented by formula I. A related application is an application of the compound in preparation of drugs for calming, mind tranquillizing, senile dementia resisting, convulsion resisting, epilepsy resisting and depression resisting.
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Paragraph 0056-0057
(2017/09/23)
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- TRIPEPTIDE COMPOUND, PREPARATION METHOD THEREFOR, AND APPLICATION THEREOF
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Provided are a tripeptide compound, a preparation method therefor, and an application thereof. The structure of the related compound is represented by formula (I). The provided compound has angiotensin converting enzyme inhibiting bioactivity, and the com
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Paragraph 0145; 0146
(2017/09/29)
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- NOVEL BETULINIC SUBSTITUTED AMIDE DERIVATIVES AS HIV INHIBITORS
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The present invention relates to novel betulinic substituted amide compounds of formula (I); and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R5, R6, R7, R8, X, Y, Z1, Z2, Z3 and are Formula (II) as defined herein. The invention novel betulinic substituted amide derivatives, related compounds, and pharmaceutical compositions useful for the therapeutic treatment of viral diseases and particularly HIV mediated diseases.
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Page/Page column 44-45
(2017/02/24)
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- Efficient and expeditious chemoselective BOC protection of amines in catalyst and solvent-free media
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A green and eco-friendly route for the almost quantitative BOC protection of a large variety of aliphatic and aromatic amines, amino acids, and amino alcohols is reported in catalyst and solvent-free media under mild reaction conditions. The products were confirmed by 1H, 13C NMR, IR spectroscopy, and in some cases, elemental analysis. This protocol does not require any water quenches, solvent separations, and purification steps, such as recrystallization and column chromatography.
- Viswanadham, Balaga,Mahomed, Abdul S.,Friedrich, Holger B.,Singh, Sooboo
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p. 1355 - 1363
(2017/02/15)
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- [TPA][Pro] ionic liquid as efficient reaction medium for N-tert-Boc protection of amines
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A facile and efficient N-tert-Boc protection of amines is described by the reaction of various primary, secondary, benzylic and aryl amines with di-tert-butyl dicarbonate in the ionic liquid [TPA][Pro] at room temperature. All the N-tert-butylcarbamates are afforded in excellent yields. A catalyst-free method was developed and the ionic liquid [TPA][Pro] can be recovered and reused for several times without loss of its activity.
- Vijaya Durga,Rambabu,Srinivasa Reddy,Hari Babu
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p. 1313 - 1316
(2017/05/02)
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- New reagent for the introduction of Boc protecting group to amines: Boc-OASUD
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A new reagent, tert-butyl (2,4-dioxo-3-azaspiro [5,5] undecan-3-yl) carbonate (Boc-OASUD) for the preparation of N-Boc-amino acids is described. The Boc-OASUD reacts with amino acids and their esters at room temperature in the presence of a base and gives N-Boc-amino acids and their esters in good yields and purity. Introduction of the Boc group takes place without racemization. The Boc-OASUD, being a solid and more stable, is a better alternative to di-tert-butyl dicarbonate which is low melting and has to be dispensed in plastic containers than glass because of its poor stability.
- Maheswara Rao, B. Leela,Nowshuddin, Shaik,Jha, Anjali,Divi, Murali K.,Rao
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p. 2127 - 2132
(2017/10/31)
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- As hepatitis c inhibitor spiro compound and its use in medicine
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The invention provides a spiro compound serving as a hepatitis c inhibitor and application thereof in a medicine. The compound is a compound as shown in a formula (I) or a stereisomer, a geometric isomer, a tautomer, nitric oxide, an aquo-complex, a solvate, a metabolite, pharmaceutically acceptable salt or prodrug of the compound as shown in the formula (I). The invention also provides a pharmaceutical composition containing the compound, application of the compound and the pharmaceutical composition in inhibition of HCV (Hepatitis C Virus) copy and HCV virus protein, as well as the application of the compound and the pharmaceutical composition in prevention, handling, treatment or relieving of HCV infection or hepatitis c disease for a patient. The formula I is as shown in the specification.
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Paragraph 0811; 1804; 1805
(2017/12/28)
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- NEW COMPOUNDS HAVING TRIPLE ACTIVITIES OF THROMBOLYSIS, ANTITHROMBOTIC AND RADICAL SCAVENGING, AND SYNTHESIS, NANO-STRUCTURE AND USE THEREOF
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The present invention relates to a compound simultaneously having triple activities of thrombolysis, antithrombosis and free radical scavenging, as well as the preparation method, composition, and applications thereof. The compound is represented by the f
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Paragraph 0090
(2016/04/19)
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- Aluminium, gallium and indium complexes supported by a chiral phenolato-prolinolato dianionic ligand
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Congeneric complexes (S)-{?O}MCH2SiMe3 (M=Al, 3; Ga, 5; In, 6) of the triel metals supported by an enantiomerically pure phenolato-alkoxo {?O}2- dianionic tridentate ligand derived from prolinol, along with their chloro derivatives, have been prepared and characterised. The aluminium-alkyl species (S)-{?O}AlMe and 3 form four-coordinate complexes with slightly distorted tetrahedral geometries, whereas the geometry in the Lewis acidic five-coordinate (S)-{?O}GaCl·THF is a distorted trigonal bipyramid. These alkyl complexes do not react cleanly, if at all, with protic sources. The indium(III) compound 6, which is for instance inert towards iPrOH or BnOH even after hours at 70°C, catalyses at 95°C the controlled, immortal ring-opening polymerisation of racemic lactide (up to 1000 equivalents) in the presence of excess BnOH as a chain transfer agent. It affords atactic, monodisperse polylactides with predictable molecular weights.
- Maudoux, Nicolas,Tan, Eric,Hu, Yuya,Roisnel, Thierry,Dorcet, Vincent,Carpentier, Jean-Fran?ois,Sarazin, Yann
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p. 131 - 143
(2016/12/14)
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- NOVEL BETULINIC PROLINE IMIDAZOLE DERIVATIVES AS HIV INHIBITORS
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The present invention relates to novel betulinic proline imidazole derivatives and related compounds, compositions useful for therapeutic treatment of viral diseases and particularly HIV mediated diseases.
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Page/Page column 20; 21
(2016/01/25)
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- Aggregation propensity of amyloidogenic and elastomeric dipeptides constituents
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This study demonstrates the self-assembly of N- and C-terminal protected dipeptides Phe–Gly and Pro–Gly which were derived from amyloidogenic and elastomeric peptide sequences. These constituents afforded nanostructured supramolecular ensembles through va
- Kumar, Vikas,Krishna, K. Vijaya,Khanna, Shruti,Joshi, Khashti Ballabh
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supporting information
p. 5369 - 5376
(2016/08/05)
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- Design, synthesis, and in vitro antiplasmodial activity of 4-aminoquinolines containing modified amino acid conjugates
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Abstract: A new series of side chain-modified 4-aminoquinolines were synthesized and screened for in vitro antiplasmodial activity against both chloroquine-sensitive (3D7) and chloroquine-resistant (K1) strains of Plasmodium falciparum. Among the series, compounds 30 and 31 showed significant inhibition of parasite growth against K1 strain of P. falciparum with IC50 values 0.28 and 0.31?μM, respectively, whereas compounds 34, 35, and 38 exhibited superior activity against K1 strain with IC50 values 0.18, 0.22, and 0.17?μM, respectively, as compared to 0.255?μM for chloroquine (CQ). All the compounds displayed good resistance factor between 1.54 and >34.48 as against 51.0 for CQ. All these analogues were found to form strong complex with hematin and inhibited the β-hematin formation in vitro, suggesting that this class of compounds act on a heme polymerization target. Overall results suggest that present series of compounds appear to be promising for further lead optimization to obtain compounds active against drug-resistant parasites. Graphical Abstract: [Figure not available: see fulltext.]
- Srinivasarao, Kondaparla,Agarwal, Pooja,Srivastava, Kumkum,Haq,Puri, Sunil K.,Katti
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p. 1148 - 1162
(2016/07/06)
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- Study of the Paternò–Büchi type photolabile protecting group and application to various acids
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An efficient photolabile protecting group, thiochromone S,S-dioxides with the diazomethyl group for phosphate derivatives, amino acids and sulfonic acids was developed. Protection and photodeprotection reactions proceeded smoothly under mild conditions without any catalyst.1H NMR and HPLC spectra studies demonstrated the photolysis properties of the photolabile protecting group and gave an exact quantification of the released substrates. Specially, the photoproduct derived from the thiochromone derivatives following Paternò–Büchi type photo-cycloaddition showed high fluorescence intensity. This fluorescent characteristic demonstrated the photodeprotection progress also can be monitored by fluorescence spectra.
- Zhang, Youlai,Zhang, Huan,Ma, Chi,Li, Junru,Nishiyama, Yasuhiro,Tanimoto, Hiroki,Morimoto, Tsumoru,Kakiuchi, Kiyomi
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supporting information
p. 5179 - 5184
(2016/11/13)
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- SPIRO COMPOUNDS AS HEPATITIS C VIRUS INHIBITORS
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Disclosed are spiro compounds of formula (I), or stereomers, geometric isomers, tautomers, nitrogen oxides, hydrates, solvates, metabolites, pharmaceutically acceptable salts or prodrugs thereof. The compounds can be used to treat hepatitis C virus (HCV) infection or hepatitis C disease. Furthermore disclosed are pharmaceutical compositions containing the compounds and the method of using the compounds or pharmaceutical compositions in the treatment of HCV infection or hepatitis C disease.
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Page/Page column 0277-0282
(2015/11/09)
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- Ring-closing metathesis approach for the synthesis of optically active l-proline-based macrocycles
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Chiral macrocyclic compounds find many interesting applications in supramolecular chemistry, such as in chiral discrimination and chiral catalysis. In this study, the synthesis of novel optically active macrocyclic compounds based on l-proline is reported
- Al-Azemi, Talal F.,Mohamod, Abdirahman A.,Vinodh, Mickey
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p. 1523 - 1528
(2015/03/04)
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- Direct asymmetric aldol reactions catalysed by trans-4-hydroxy-(S)-prolinamide in solvent-free conditions
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Direct asymmetric aldol reactions between 4-nitrobenzaldehyde and cyclohexanone were catalysed by trans-4-hydroxy-(S)-prolinamide (10 mol %) in the presence of CH3COOH (10 mol %) as the co-catalyst under solvent-free conditions at 15 °C. (2S,4R)-4-Hydroxy-N-((S)-1-phenylethyl)pyrrolidine-2-carboxamide 2 efficiently catalysed the asymmetric aldol reaction to afford the product in >99% yield and with 95% ee with an anti/syn ratio of 88:12 after 18 h. The additional trans-hydroxyl group on (S)-prolinamide and (S)-1-phenylethylamine both influenced the ee of the predominant anti aldol product. Different benzaldehyde derivatives with cyclohexanone gave the corresponding aldol products in 38-89% yields and with 56-94% ee with anti/syn (100:0-71:29). Catalyst 2 can be used up to 5 continuous cycles for asymmetric aldol reactions between 4-nitrobenzaldehyde and cyclohexanone with overall 91% yield and 86% yield of anti-product with anti/syn (98:2).
- Yadav, Geeta Devi,Singh, Surendra
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p. 1156 - 1166
(2015/10/28)
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- Complementary stereochemical outcomes in proline-based self-regenerations of stereocenters
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Stereoselective alkylations of proline-based amino amides are described, where high levels of either a cis or trans configuration can be attained simply by the choice of the aminal group. Isobutryaldehyde-derived aminals provide the cis configuration, whi
- Knight, Brian J.,Stache, Erin E.,Ferreira, Eric M.
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supporting information
p. 432 - 435
(2014/04/03)
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- General solvent-free highly selective N-tert-butyloxycarbonylation strategy using protic ionic liquid as an efficient catalyst
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A simple, rapid and solvent-free protocol is described for the chemo-selective transformation of amines to tert-butyloxycarbonyl protected derivatives (NHBoc) using Boc2O and imidazolium trifluoroacetate protic ionic liquid (5-20 mol%). Unwanted side products such as isocyanate, urea or N,N-di-Boc were not detected. The scope of the protection strategy was successfully explored for substrate alcohols, phenols and thiol at elevated temperatures. Optically pure amino acids, amino acid esters and amino alcohols were efficiently converted to the corresponding N-Boc protected derivatives in excellent yields without racemization at the chiral center. The distinct advantages of this method are: operational simplicity, cleaner reaction, high selectivity, excellent yield, rapid reaction convergence, easy preparation and recyclability of the catalyst.
- Majumdar, Swapan,De, Jhinuk,Chakraborty, Ankita,Maiti, Dilip K.
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p. 24544 - 24550
(2014/07/07)
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- A small molecule peptidomimetic that binds to c-KIT1 G-quadruplex and exhibits antiproliferative properties in cancer cells
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A modular synthesis of l-proline derived peptidomimetics has been developed using the CuI catalyzed Huisgen cycloaddition between an azido prolinamide with pyridine and benzene dicarboxamide containing dialkynes. F?rster Resonance Energy Transfer (FRET) melting assay provided an initial indication that the pyridyl analogue can stabilize the c-KIT1 quadruplex DNA. A competitive FRET-melting assay and Fluorescent Intercalator Displacement (FID) assay suggest that the pyridyl ligand shows excellent selectivity for c-KIT1 quadruplex over duplex DNA and other investigated G-quadruplexes. Molecular docking studies indicate that the pyridyl ligand can adopt unique conformations upon binding to c-KIT1 quadruplex due to the presence of intramolecular hydrogen bonds. The pyridyl ligand can perturb cell cycle progression and induce necrotic cell death of human hepatocellular liver carcinoma HepG2 cells.
- Chauhan, Ajay,Paladhi, Sushovan,Debnath, Manish,Mandal, Samir,Das, Rabindra Nath,Bhowmik, Sudipta,Dash, Jyotirmayee
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supporting information
p. 4422 - 4429
(2014/11/08)
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- NOVEL BETULINIC ACID PROLINE DERIVATIVES AS HIV INHIBITORS
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The invention relates to novel betulinic acid derivatives and related compounds, and pharmaceutical compositions useful for the therapeutic treatment of viral diseases and particularly HIV mediated diseases. These compounds are esterified in position 3 and are substituted in position 17 of the betulinic acid structure, via a linking group W, by a saturated 5-7 membered nitrogen-heterocycle.
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Paragraph 0158
(2014/07/21)
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- Evaluation of mono- and dipeptides as organocatalysts for enantioselective aldol reaction
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Catalytic activities of (3S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (THIQA)-based mono- and dipeptides and their l-proline analogs in asymmetric aldol reaction were investigated. THIQA-based dipeptides showed better enantioselectivity than proli
- Yolacan, Cigdem,Mavis, Murat Emrah,Aydogan, Feray
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p. 3707 - 3713
(2014/05/20)
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- Encapsulation of a catalytic imidazolium salt into avidin: Towards the development of a biohybrid catalyst active in ionic liquids
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Herein, we report the development of biohybrid catalysts that are capable of catalyzing the aldol reaction. The use of biotinylated imidazolium salts in combination with racemic or enantiomerically pure catalytic anions allowed us to study the adaptive and cooperative positioning of the anionic catalyst inside the protein. Supramolecular encapsulation of the biotinylated catalyst into avidin resulted in good selectivity for the aldol reaction performed in ionic liquid/water mixtures. Biohybrid catalysts capable of catalyzing the aldol reaction are prepared from avidin and biotinylated imidazolium salts with either racemic or enantiomerically pure catalytic anions. Supramolecular encapsulation (see figure) of the biotinylated catalyst in avidin resulted in good selectivities for the aldol reaction when performed in ionic liquid/water mixtures and the adaptive and cooperative positioning of the anionic catalyst inside the avidin protein is discussed. Copyright
- Gauchot, Vincent,Branca, Mathieu,Schmitzer, Andreea
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supporting information
p. 1530 - 1538
(2014/03/21)
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- Design, synthesis and biological evaluation of hetero-aromatic moieties substituted pyrrole-2-carbonitrile derivatives as dipeptidyl peptidase IV inhibitors
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A series of novel hetero-aromatic moieties substituted α-amino pyrrole-2-carbonitrile derivatives was designed and synthesized based on structure-activity relationships (SARs) of pyrrole-2-carbonitrile inhibitors. All compounds demonstrated good dipeptidyl peptidase IV (DPP4) inhibitory activities (IC50 = 0.004-113.6 μM). Moreover, compounds 6h (IC50 = 0.004 μM) and 6n (IC50 = 0.01 μM) showed excellent inhibitory activities against DPP4, good selectivity (compound 6h, selective ratio: DPP8/DPP4 = 450.0; DPP9/DPP4 = 375.0; compound 6n, selective ratio: DPP8/DPP4 = 470.0; DPP9/DPP4 = 750.0) and good efficacy in an oral glucose tolerance test in ICR mice. Furthermore, compounds 6h and 6n demonstrated moderate PK properties (compound 6h, F% = 37.8%, t1/2 = 1.45 h; compound 6n, F% = 16.8%, t1/2 = 3.64 h).
- Ji, Xun,Su, Mingbo,Wang, Jiang,Deng, Guanghui,Deng, Sisi,Li, Zeng,Tang, Chunlan,Li, Jingya,Li, Jia,Zhao, Linxiang,Jiang, Hualiang,Liu, Hong
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supporting information
p. 111 - 122
(2014/03/21)
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