- Asymmetrical nonbridgehead nitrogen-IV. Chiroptical properties of the amines, N-chloroamines and cyanamides
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The ORD and CD spectra of 2-methyl-aziridine, azetidine, pyrrolidine, piperidine, their N-Me, N-Hal, N-CN derivatives as well as those of camphidine, N-methyl- and N-cyano-camphidine have been investigated. The possibility of application of the quadrant rule for N-chloroamines is discussed. A similar rule is proposed for the N-CN chromophore.
- Kostyanovsky,Gella,Markov,Samojlova
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Read Online
- Stereoselective total synthesis of (+)-azimic acid
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An efficient synthesis of enantiopure (+)-azimic acid has been developed, utilizing easily available amino acid L-alanine as a chiral pool starting material.
- Kumara,Datta
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Read Online
- Calothrixamides A and B from the Cultured Cyanobacterium Calothrix sp. UIC 10520
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Cyanobacteria are a source of chemically diverse metabolites with potential medicinal and biotechnological applications. Rapid identification of compounds is central to expedite the natural product discovery process. Mass spectrometry has been shown to be an important tool for dereplication of complex natural product samples. In addition, chromatographic separation and complementary spectroscopic analysis (e.g., UV) can enhance the confidence of the dereplication process. Here, we applied a droplet-liquid microjunction-surface sampling probe (droplet probe) coupled with UPLC-PDA-HRMS-MS/MS to identify two new natural products in situ from the freshwater strain Calothrix sp. UIC 10520. This allowed us to prioritize this strain for chemical investigation based on the presence of new metabolites very early in our discovery process, saving both time and resources. Subsequently, calothrixamides A (1) and B (2) were isolated from large-scale cultures, and the structures were elucidated by 1D and 2D NMR spectroscopy and mass spectrometry. The absolute configurations were determined by a combination of chemical degradation reactions, derivatization methods (Mosher's, Marfey's, and phenylglycine methyl ester), and J-based configurational analysis. Calothrixamides showed no cytotoxic activity against the MDA-MB-435, MDA-MB-231, and OVCAR3 cancer cell lines. They represent the first functionalized long-chain fatty acid amides reported from the Calothrix genus and from a freshwater cyanobacterium.
- Crnkovic, Camila M.,Krunic, Aleksej,May, Daniel S.,Wilson, Tyler A.,Kao, Diana,Burdette, Joanna E.,Fuchs, James R.,Oberlies, Nicholas H.,Orjala, Jimmy
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Read Online
- Enabling an atom-economic production of chiral amino alcohols by electrodialysis with bipolar membranes
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Optically pure amino alcohols are widely used as essential building blocks of catalysts and auxiliaries in asymmetric synthesis, especially in pharmaceuticals. Catalytic hydrogenation has been regarded as the most effective route to produce chiral amino alcohols, but it is still unsatisfactory, which mainly manifests in the involvement of extra acids and bases, thus generating a large amount of inorganic salt byproducts, along with a relatively low yield. In this paper, we propose a novel approach that integrates catalytic hydrogenation and electrodialysis with bipolar membranes (EDBM) to produce pure chiral amino alcohols in a completely green way. EDBM tackles the sustainability issue by splitting the resulting salt of the hydrogenation into the corresponding acid and base (amino alcohol solutions), and the acid could be reused in the next batch directly and a closed loop forms. Here, as a model system to demonstrate the feasibility, a biorenewable chiral l-alanine solid and clean H2 gas are used as the feed stocks and finally converted into a pure l-alaninol product successfully, with no discharge of harmful substances. Furthermore, three typical mineral acids (H3PO4, H2SO4 and HCl) have been investigated systematically and achieved similar performances. The results of all tests and the cost analysis strongly suggest that this new approach is widely applicable, highly productive and sustainable. It demonstrates a true atomically economic route to produce chiral amino alcohols and entirely meets the requirements of green chemistry.
- Cao, Chang-Yan,Chen, Qing,Du, Ming-Gu,Gao, Wei-Ting,Song, Wei-Guo,Zhang, Wei-Ming
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Read Online
- Stereoretentive C-H bond activation in the aqueous phase catalytic hydrogenation of amino acids to amino alcohols
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(Matrix presented) At 100°C and 1000 psi of hydrogen, aqueous L-alanine undergoes facile hydrogenation to L-alaninol over a 5% Ru/C catalyst. In the presence of added acid to protonate the carboxylate moiety, the reaction is faster and more selective than analogous reductions of simple alkanoic acids. Stereochemistry at the α-carbon is retained despite complete exchange of hydrogen at this site, as shown by deuterium incorporation. Similar stereoretentive C-H bond activation at C2 is seen in L-alaninol itself, and when acid is omitted, in L-alanine. These processes reveal a class of mild, highly stereoretentive C-H bond activations occurring in water over a heterogeneous catalyst.
- Jere, Frank T.,Miller, Dennis J.,Jackson, James E.
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Read Online
- Expansion of substrate scope for nitroxyl radical/copper-catalyzed aerobic oxidation of primary alcohols: A guideline for catalyst selection
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Four distinctive sets of optimum nitroxyl radical/copper salt/additive catalyst combinations have been identified for accommodating the aerobic oxidation of various types of primary alcohols to their corresponding aldehydes. Interestingly, less nucleophilic catalysts exhibited higher catalytic activities for the oxidation of particular primary allylic and propargylic alcohols to give α,β-unsaturated aldehydes that function as competent Michael acceptors. The optimum conditions identified herein were successful in the oxidation of various types of primary alcohols, including unprotected amino alcohols and divalent-sulfur-containing alcohols in good-to-high yields. Moreover, N-protected alaninol, an inefficient substrate in the nitroxyl radical/ copper-catalyzed aerobic oxidation, was oxidized in good yield. On the basis of the optimization results, a guideline for catalyst selection has been established.
- Iwabuchi, Yoshiharu,Nagasawa, Shota,Sasaki, Ryota,Sasano, Yusuke,Yamaichi, Aoto
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p. 488 - 497
(2021/05/27)
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- Selective hydrogenation of primary amides and cyclic di-peptides under Ru-catalysis
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A ruthenium(II)-catalyzed selective hydrogenation of challenging primary amides and cyclic di-peptides to their corresponding primary alcohols and amino alcohols, respectively, is reported. The hydrogenation reaction operates under mild and eco-benign conditions and can be scaled-up.
- Subaramanian, Murugan,Sivakumar, Ganesan,Babu, Jessin K.,Balaraman, Ekambaram
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supporting information
p. 12411 - 12414
(2020/10/30)
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- Data mining of amine dehydrogenases for the synthesis of enantiopure amino alcohols
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Chiral amino alcohols are essential building blocks for the pharmaceutical industry, and are widely present in natural and synthetic bioactive compounds. Amine dehydrogenases (AmDHs) can asymmetrically reduce prochiral ketones with low-cost ammonia to chiral amines and water as by-products, using NAD(P)H as a cofactor under mild conditions, but hydroxy ketones with formation of chiral hydroxy amines have rarely been investigated. In this study, six new bacterial AmDHs derived from amino acid dehydrogenases (AADHs) were identified by data mining, and five out of the six enzymes were able to efficiently reduce 1-hydroxybutan-2-one (1a) to (S)-2-aminobutan-1-ol ((S)-2a) with 19-99% conversions and 99% ee. The five AmDHs were purified and biochemically characterized for reductive amination activity towards substrate 1a with the optimal pH at 8.5 or 9.0 and the optimal temperature at 45 °C, 50 °C or 55 °C, and provided reductive amination of a broad range of prochiral α-hydroxy ketones, and even of a model β-hydroxy ketone leading to β-hydroxy amine with 99% ee. Our study expands the toolbox of AmDHs in the synthesis of chiral amino alcohols.
- Guo, Jinggong,Li, Jun-Kuan,Ma, Jun-An,Miao, Yuchen,Qu, Ge,Sun, Zhoutong,Wang, Hongyue
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p. 5945 - 5952
(2020/10/08)
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- Synthesis of Enantiopure PZM21: A Biased Agonist of the Mu-Opioid Receptor
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PZM21 (1) was recently reported as a biased agonist of the mu-opioid receptor (MOR) with improved antinociceptive effects and reduced side effects compared with traditional opioid-based analgesics. The original synthesis of PZM21 with the desired (S,S) configuration required the separation of a diastereomeric mixture in the final step by using chiral HPLC. A concise synthesis of 1 has now been developed in the enantiomeric pure form starting with commercially available l-alanine and proceeding via a chiral aziridine as a key intermediate. The final product was obtained as the (S,S) diastereomer in seven steps in 22.5 % yield from l-alanine. This synthetic strategy could be readily applied to the development of PZM21 analogues at the thiophenyl position.
- Perrey, David,Zhang, Dehui,Nguyen, Thuy,Carroll, F. Ivy,Ko, Mei-Chuan,Zhang, Yanan
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p. 4006 - 4012
(2018/07/30)
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- SYNTHESIS OF LEVOMETHADONE HYDROCHLORIDE OR DEXTROMETHADONE HYDROCHLORIDE AND METHODS FOR USE THEREOF
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Highly efficient methods for synthesis of levomethadone hydrochloride or dextromethadone hydrochloride are provided starting from D-alanine, or L-alanine, respectively, with retention of configuration. Methods for treating a subject are provided comprising administering a composition comprising an effective amount of levomethadone hydrochloride having not more than 10 ppm dextromethadone.
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Paragraph 00348; 00349
(2017/03/14)
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- Heterogeneous Catalytic Hydrogenation of Chiral Amino Acid Methyl Esters to Amino Alcohols with Retention of Configuration Over Mg-Modified Cu/ZnO/Al2O3 Catalyst
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Selective hydrogenation of amino acid methyl esters to chiral amino alcohols is an important and fascinating process. The CuZn0.3Mg0.1AlOx catalyst for the synthesis of chiral amino alcohols was prepared by the fractional
- Zhan, Bing,Zhang, Shuangshuang,Yu, Jun,Xiao, Xiuzheng,Guo, Xiaoming,Mao, Dongsen,Lu, Guanzhong
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p. 2160 - 2166
(2017/07/25)
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- Method for preparing L-2-aminopropanol by means of splitting DL-2-aminopropanol
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The invention relates to a method for preparing L-2-aminopropanol by means of splitting DL-2-aminopropanol. The method includes steps of 1), dissolving L-tartaric acid in water to obtain L-tartaric acid aqueous solution; 2), dissolving the DL-2-aminopropanol in alcohol solvents at the room temperature, then stirring the DL-2-aminopropanol and the alcohol solvents under cooling conditions, simultaneously completely dropwise adding the L-tartaric acid aqueous solution into the DL-2-aminopropanol to obtain mixed solution, then cooling the mixed solution until the temperature of the mixed solution reaches 0-5 DEG C, and preserving heat to obtain cooled solution; 3), adding a small quantity of crystal seeds into the cooled solution, allowing the cooled solution to stand still at the temperatures ranging from -15 DEG C to +25 DEG C, crystallizing the cooled solution at the temperatures ranging from -15 DEG C to +25 DEG C for 16-24 hours and separating out L-tartaric acid-L-2-aminopropanol acid salt crystals; 4), dissolving the L-tartaric acid-L-2-aminopropanol acid salt crystals by the aid of alcohol solvents, adding inorganic bases into the L-tartaric acid-L-2-aminopropanol acid salt crystals in batches, stirring the inorganic bases and the L-tartaric acid-L-2-aminopropanol acid salt crystals until amino alcohol is completely free, carrying out suction filtration and carrying out reduced-pressure distillation on filter liquid to obtain the L-2-aminopropanol. The method has the advantages that processes are easy to implement, raw materials are high in utilization rate, and accordingly the method is suitable for large-scale production.
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Paragraph 0021; 0022; 0024; 0027; 0030
(2017/08/29)
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- Design, synthesis and effect of the introduction of a propargyloxy group on the fungicidal activities of 1-substituted phenoxypropan-2-amino valinamide carbamate derivatives
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The cell walls of oomycetes are composed of cellulose, making cellulose synthase enzymes good targets for carboxylic acid amide fungicides. Valinamide carbamates are amino acid fungicides that represent excellent alternatives to conventional synthetic pesticides in terms of their ability to reduce the negative impacts of these compounds on human health and the environment. In a continuation of our research towards the development of new cellulose synthase inhibitors, we have developed a series of "stretched" analogues of iprovalicarb by the introduction of an additional OCH2 linker. The bioassay results indicated that compounds containing a small group at the para-position of phenyl gave excellent fungicidal activities with EC50 values ranging from 0.59 to 2.06 μmol L-1. Most notably, the introduction of a propargyloxy group led to a pronounced increase in the fungicidal activity. Furthermore, compound 7o bearing a propargyloxy group was identified as the most promising candidate because of its excellent fungicidal potency against oomycete diseases and good fungicidal activity against non-oomycete diseases.
- Li, Jian-Qiang,Wang, Zhi-Peng,Gao, Yang,Zhao, Wei-Guang
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p. 82131 - 82137
(2016/09/09)
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- Design, Synthesis, Fungicidal Activity, and Unexpected Docking Model of the First Chiral Boscalid Analogues Containing Oxazolines
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Chirality greatly influences the biological and pharmacological properties of a pesticide and will contribute to unnecessary environmental loading and undesired ecological impact. No structure and activity relationship (SAR) of enantiopure succinate dehydrogenase inhibitors (SDHIs) was documented during the structure optimization of boscalids. On the basis of commercial SDHIs, oxazoline natural products, and versatile oxazoline ligands in organic synthesis, the first effort was devoted to explore the chiral SDHIs and the preliminary mechanism thereof. Fine-tuning furnished chiral nicotinamides 4ag as a more promising fungicidal candidate against Rhizoctonia solani, Botrytis cinerea, and Sclerotinia sclerotiorum, with EC50 values of 0.58, 0.42, and 2.10 mg/L, respectively. In vivo bioassay and molecular docking were investigated to explore the potential in practical application and plausible novelty in action mechanism, respectively. The unexpected molecular docking model showed the different chiral effects on the binding site with the amino acid residues. This chiral nicotinamide also featured easy synthesis and cost-efficacy. It will provide a powerful complement to the commercial SDHI fungicides with the introduction of chirality.
- Li, Shengkun,Li, Dangdang,Xiao, Taifeng,Zhang, Shasha,Song, Zehua,Ma, Hongyu
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p. 8927 - 8934
(2016/12/07)
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- Enantiodivergent Synthesis of (+)- and (?)-Pyrrolidine 197B: Synthesis of trans-2,5-Disubstituted Pyrrolidines by Intramolecular Hydroamination
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A highly efficient, diastereoselective, iron(III)-catalyzed intramolecular hydroamination/cyclization reaction involving α-substituted amino alkenes is described. Thus, enantiopure trans-2,5-disubstituted pyrrolidines and trans-5-substituted proline derivatives were synthesized by means of a combination of enantiopure starting materials, easily available from l-α-amino acids, with sustainable metal catalysts such as iron(III) salts. The scope of this methodology is highlighted in an enantiodivergent approach to the synthesis of both (+)- and (?)-pyrrolidine 197B alkaloids from l-glutamic acid. In addition, a computational study was carried out to gain insight into the complete diastereoselectivity of the transformation.
- Pérez, Sixto J.,Purino, Martín A.,Cruz, Daniel A.,López-Soria, Juan M.,Carballo, Rubén M.,Ramírez, Miguel A.,Fernández, Israel,Martín, Víctor S.,Padrón, Juan I.
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supporting information
p. 15529 - 15535
(2016/10/13)
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- Insight into the mechanism of hydrogenation of amino acids to amino alcohols catalyzed by a heterogeneous MoOx-modified Rh catalyst
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Hydrogenation of amino acids to amino alcohols is a promising utilization of natural amino acids. We found that MoOx-modified Rh/SiO2 (Rh-MoOx/SiO2) is an efficient heterogeneous catalyst for the reaction at low temperature (323 K) and the addition of a small amount of MoOx drastically increases the activity and selectivity. Here, we report the catalytic potential of Rh-MoOx/SiO2 and the results of kinetic and spectroscopic studies to elucidate the reaction mechanism of Rh-MoOx/SiO2 catalyzed hydrogenation of amino acids to amino alcohols. Rh-MoOx/SiO2 is superior to previously reported catalysts in terms of activity and substrate scope. This reaction proceeds by direct formation of an aldehyde intermediate from the carboxylic acid moiety, which is different from the reported reaction mechanism. This mechanism can be attributed to the reactive hydride species and substrate adsorption caused by MoOx modification of Rh metal, which results in high activity, selectivity, and enantioselectivity.
- Tamura, Masazumi,Tamura, Riku,Takeda, Yasuyuki,Nakagawa, Yoshinao,Tomishige, Keiichi
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p. 3097 - 3107
(2015/02/05)
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- HIV INTEGRASE INHIBITORS
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The present invention features compounds that are HIV integrase inhibitors and therefore are useful in the inhibition of HIV replication, the prevention and/or treatment of infection by HIV, and in the treatment of AIDS and/or ARC.
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- An easy 'Filter-and-Separate' method for enantioselective separation and chiral sensing of substrates using a biomimetic homochiral polymer
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We present a polyfluorene appended with protected l-glutamic acid that exhibited a reversible α-helix/β-sheet-like conformation and helical porous fibrous morphology mimicking the super-structure of proteins. The new homochiral polymer probe enabled efficient heterogeneous enantioselective separation and chiral sensing of a wide variety of substrates from their aqueous racemic mixture using an easy 'Filter-and-Separate' method.
- Senthilkumar,Asha
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supporting information
p. 8931 - 8934
(2015/05/27)
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- A new enantioselective synthesis of the anti-Parkinson agent safinamide
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An alternative highly enantioselective synthesis of the anti-Parkinson agent safinamide from simple, commercially available, starting materials is described. The protocol might also be useful in the synthesis of structural variants of safinamide, such as ralfinamide or related analogues. Georg Thieme Verlag Stuttgart New York.
- Reddi, Anjaneyulu,Mujahid, Mohammad,Sasikumar, Murugesan,Muthukrishnan, Murugan
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p. 1751 - 1756
(2014/07/08)
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- AN IMPROVED SYNTHESIS OF ANTI-PARKINSON AGENT
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The present invention relates to an improved process for synthesis of anti-Parkinson compound of formula (I) from commercially available (R)-benzyl glycidyl ether, wherein the compound obtained has enantiopurity greater than >98%. Formula (I) wherein R1 and R2 are each independently selected from hydrogen or halogen.
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Page/Page column 14-15
(2014/11/13)
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- Catalytic hydrogenation of amino acids to amino alcohols with complete retention of configuration
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Rh-MoOx/SiO2 is an effective heterogeneous catalyst for selective hydrogenation of amino acids to amino alcohols in a water solvent. MoOx modification of Rh drastically enhanced the activity and improved the selectivity and ee. Various amino alcohols were obtained in high yields (90-94%) with complete retention of configuration. This journal is the Partner Organisations 2014.
- Tamura, Masazumi,Tamura, Riku,Takeda, Yasuyuki,Nakagawa, Yoshinao,Tomishige, Keiichi
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supporting information
p. 6656 - 6659
(2014/06/10)
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- NOVEL TRIAZINE COMPOUNDS
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The present invention relates to novel triazine compounds of formula (1). The present invention also discloses compounds of formula I along with other pharmaceutical ac-ceptable excipients and use of the compounds to modulate the PI3K/ mTOR pathway
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Page/Page column 126; 127
(2014/02/16)
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- New chiral 4-substituted 2-cyanoethyl-oxazolines: Synthesis and assessment of some biological activities
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This paper describes the synthesis of new enantiomerically pure 2-cyanoethyl-oxazolines in one step starting from a wide range of amino alcohols and 4-ethoxy-4-iminobutanenitrile with high to good yields (73-96%) via an appropriate procedure which can be used for a selective synthesis of mono-oxazolines. A simple operation as well as a practical separation is additional eco-friendly attributes of this method. All the synthesized compounds were identified and characterized with their physicochemical features and their spectral data (1H NMR, 13C NMR and TOFMS ES+). Among the prepared mono-oxazolines, the mono-oxazoline (3a) [3-[(4S)-4-benzyl-4,5-dihydro-1,3-oxazol-2-yl] propanenitrile] was tested to detect some biological activities. This compound was studied in vitro given the various types of pharmacological properties characterizing these compounds such as antioxidant, antimicrobial and analgesic activities. The antioxidant activity and mechanism of (3a) were identified using various in vitro antioxidant assays including 1,1-diphenyl-2-picryl-hydrazyl (DPPH), and superoxide anion radicals (O2-) scavenging activity. In addition, compared to Quercetin, the tested synthetic product reveals a relatively-strong antiradical activity towards the DPPH (activity percentage of 81.22%) free radicals and significantly decreased the reactive oxygen species such as (O2 -) formation evaluated by the non-enzymatic (nitroblue tetrazolium/riboflavine) and the enzymatic (xanthine/xanthine oxidase) systems. Related activity values were, respectively, 66% and 60.30%. The oxazoline (3a) showed a high ability to reduce the O2- generation and proved to be a very potent radical scavenger. On the other hand, the analgesic property of the 3[(4S)-benzyl-4,5-dihydro-1,3-oxazol-2-yl] propanenitrile (3a) was demonstrated. The subcutaneous administration of (3a) produced a significant reduction in the number of abdominal constrictions amounting to 73.81% in the acetic acid writhing test in mice. In addition to these advances, the oxazoline (3a) has been investigated as an antimicrobial agent. Our results showed that this molecule exhibited various levels of antibacterial effect against all the tested bacterial strains.
- Hassani, Rym,Kacem, Yakdhane,Ben Mansour, Hedi,Ben Ammar, Hamed,Ben Hassine, Béchir
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- 2,3-DIHYDROIMIDAZOL[1,2-C]PYRIMIDIN-5(1H)-ONE BASED LIPOPROTEIN-ASSOCIATED PHOSPHOLIPASE A2 (LP-PLA2) INHIBITORS
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The present invention relates to novel compounds that inhibit Lp-PLA2 activity, processes for their preparation, to compositions containing them and to their use in the treatment of diseases associated with the activity of Lp-PLA2, for example atherosclerosis, Alzheimer's disease.
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Page/Page column 28
(2014/08/07)
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- COMPOUNDS
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The present invention relates to novel compounds that inhibit Lp-PLA2 activity, processes for their preparation, to compositions containing them and to their use in the treatment of diseases associated with the activity of Lp-PLA2, for example atherosclerosis, Alzheimer's disease.
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Paragraph 0179; 0180; 0181
(2014/08/07)
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- NO-RELEASING NONOATE (NITROGEN-BOUND) SULFONAMIDE-LINKED-COXIB ANTI-CANCER AGENTS
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The present invention provides NO-releasing NONOate(nitrogen bound)sulfonamide- linked-coxib anti-cancer agents, having the structure of Formula (I): wherein R1, X, L, R2, R3, R4, and Z are as defined in the detailed description; pharmaceutical compositions comprising at least one compound of Formula (I); and methods useful for healing wounds, preventing and treating cancer, or treating actinic keratosis, cystic fibrosis or acne, using a compound of Formula (I).
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Paragraph 0081; 0082
(2014/02/15)
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- Ionic liquid crystals derived from amino acids
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Novel chiral amino acid derived ionic liquid crystals with amine and amide moieties as spacers between the imidazolium head group and the alkyl chain were synthesised. The key step in the synthesis utilised the relatively uncommon SO3 leaving group in a microwave-assisted reaction. The mesomorphic properties of the mesogens were determined by differential scanning calorimetry (DSC), polarising optical microscopy (POM) and X-ray diffraction. All liquid crystalline salts exhibit a smecticA mesophase geometry with strongly interdigitated bilayer structures. An increase of the steric bulk of the stereogenic centre hindered the formation of mesophases. In case of phenylalanine-derived derivatives a mesomorphic behaviour was observed for shorter alkyl chains as compared to other amino acid derivatives indicating an additional stabilising effect by the phenyl moiety. Ionic liquid crystals from amino acids: Novel chiral amino acid derived imidazolium salts with amine or amide units were prepared through the sulfamidate. Depending on the steric bulk of the R group, the chain lengths and the type of anion X, stable SmA phases were detected (see scheme; Bn=benzyl). Copyright
- Mansueto, Markus,Frey, Wolfgang,Laschat, Sabine
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supporting information
p. 16058 - 16065
(2014/04/03)
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- Two modes of asymmetric polymerization of phenylacetylenes having an L -amino alcohol residue and two hydroxy groups
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Four novel chiral phenylacetylenes having an L-amino alcohol residue and two hydroxymethyl groups were synthesized and polymerized by an achiral catalyst ((nbd)Rh+[η6-(C6H5)B -(C6H5)3]) or a chiral catalytic system ([Rh(nbd)Cl]2/(S)- or (R)-phenylethylamine ((S)- or (R)-PEA)). The two resulting polymers having an L-valinol or L-phenylalaninol residue showed Cotton effects at wavelengths around 430 nm. This observation indicated that they had an excess of one-handed helical backbones. Positive and negative Cotton effects were observed only for the polymers having an L-valinol residue produced by using (R)- and (S)-PEA as a cocatalyst, respectively, although the monomer had the same chirality. Even when the achiral catalyst was used, the two resulting polymers having an L-valinol or L-phenylalaninol residue showed Cotton effects despite the long distance between the chiral groups and the main chain. We have found the first example of a new type of chiral monomer, that is, a chiral phenylacetylene monomer having an L-amino alcohol residue and two hydroxy groups that was suitable for both modes of asymmetric polymerization, that is, the helix-sense-selective polymerization (HSSP) with the chiral catalytic system and the asymmetric-induced polymerization (AIP) with the achiral catalyst. The other two monomers having L-alaninol and L-tyrosinol were found to be unsuitable to neither HSSP nor AIP because of their polymers' low solubility.
- Jia, Hongge,Li, Jun,Zang, Yu,Aoki, Toshiki,Teraguchi, Masahiro,Kaneko, Takashi
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p. 5134 - 5143
(2013/01/15)
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- New methods for the preparation of aryl 2-iminoimidazolidines
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A divergent strategy for the synthesis of 1-aryl- and 2-aryl-2- iminoimidazolidines is presented. Cyclization of N-Boc-N′-aryl-N″- (2-hydroxyethyl)guanidines in the presence of methanesulfonyl chloride and triethylamine or sodium hydride at 0 °C affords the corresponding 2-iminoimidazolidines in good yields.
- O'Donovan, Daniel H.,Rozas, Isabel
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supporting information; experimental part
p. 4532 - 4535
(2012/10/07)
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- Synthesis and in vitro antitumor activity of asperphenamate derivatives as autophagy inducer
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In an effort to improve the aqueous solubility and the antitumor activity of natural product asperphenamate, we have designed and synthesized three series of asperphenamate derivatives, including series I (simplifying molecular skeleton series), series II (introducing a hydroxyl group to A-phenyl ring series) and series III (disrupting molecular planarity series). All derivatives have displayed a significantly increased solubility compared with asperphenamate. Their growth inhibitory activities in vitro were screened by the standard MTT method in MCF-7, HeLa, and BEL-7402 cell lines. With the exception of the derivatives in series I, most of derivatives in series II and series III showed growth inhibitory activity. Among all derivatives, IM23b in series III showed the greatest potency in human breast cancer MCF-7 cells. The cellular potency of IM23b was approximately 1.5-fold more potent than that of cisplatin. The mechanism of cell death induced by IM23b in human breast cancer MCF-7 cells was further investigated. We concluded that the cell death was induced by autophagy instead of apoptosis or cell cycle arrest.
- Yuan, Lei,Li, Yanchun,Zou, Chunyang,Wang, Chao,Gao, Jian,Miao, Caixia,Ma, Enlong,Sun, Tiemin
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scheme or table
p. 2216 - 2220
(2012/04/18)
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- Optically active, amphiphilic poly(meta -phenylene ethynylene)s: Synthesis, hydrogen-bonding enforced helix stability, and direct AFM observation of their helical structures
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Optically active, amphiphilic poly(meta-phenylene ethynylene)s (PPEa) bearing l- or d-alanine-derived oligo(ethylene glycol) side chains connected to the backbone via amide linkages were prepared by microwave-assisted polycondensation. PPEa's exhibited an intense Cotton effect in the π-conjugated main-chain chromophore regions in various polar and nonpolar organic solvents due to a predominantly one-handed helical conformation stabilized by an intramolecular hydrogen-bonding network between the amide groups of the pendants. The stable helical structure was retained in the bulk and led to supramolecular column formation from stacked helices in oriented polymer films as evidenced by X-ray diffraction. Atomic force microscopy was used to directly visualize the helical structures of the polymers in two-dimensional crystalline layers with molecular resolution, and, for the first time, their absolute helical senses could unambiguously be determined.
- Banno, Motonori,Yamaguchi, Tomoko,Nagai, Kanji,Kaiser, Christian,Hecht, Stefan,Yashima, Eiji
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supporting information; scheme or table
p. 8718 - 8728
(2012/06/30)
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- Synthesis of imidacloprid derivatives with a chiral alkylated imidazolidine ring and evaluation of their insecticidal activity and affinity to the nicotinic acetylcholine receptor
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A series of imidacloprid (IMI) derivatives with an alkylated imidazolidine ring were asymmetrically synthesized to evaluate their insecticidal activity against adult female housefly, Musca domestica, and affinity to the nicotinic acetylcholine receptor of the flies. The bulkier the alkyl group, the lower was the receptor affinity, but the derivatives methylated and ethylated at the R-5-position of the imidazolidine ring were equipotent to the unsubstituted compound. Quantitative structure-activity relationship (QSAR) analysis of the receptor affinity demonstrated that the introduction of a substituent into the imidazolidine ring was fundamentally disadvantageous, but the introduction of a substituent at the R-5-position was permissible in the case of its small size. The binding model of the synthesized derivatives with the receptor supported the QSAR analysis, indicating the existence of space for a short alkyl group around the R-5-position in the ligand-binding site. In addition, positive correlation was observed between the insecticidal activity and receptor affinity, suggesting that the receptor affinity was the primary factor in influencing the insecticidal activity even if the imidazolidine ring was modified.
- Nishiwaki, Hisashi,Kuriyama, Mituhiro,Nagaoka, Hikaru,Kato, Akira,Yamauchi, Satoshi,Shuto, Yoshihiro,Akamatsu, Miki
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p. 6305 - 6312,8
(2012/12/11)
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- ω-Transaminase-catalyzed kinetic resolution of chiral amines using l-threonine as an amino acceptor precursor
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Kinetic resolution of chiral amines using l-threonine as a cosubstrate was demonstrated by a biocatalytic strategy in which (S)-selective ω-transaminase (ω-TA) was coupled with threonine deaminase (TD), eliminating the need to use an expensive keto acid as an amino acceptor. The coupled enzyme reaction enabled simultaneous production of enantiopure (R)-amine and l-homoalanine which are pharmaceutically important building blocks. To extend the versatility of this strategy to production of both enantiomers of chiral amines, (R)-selective ω-TA coupled with TD was employed to produce (S)-amine.
- Malik, M. Shaheer,Park, Eul-Soo,Shin, Jong-Shik
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supporting information; experimental part
p. 2137 - 2140
(2012/09/25)
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- One-pot and microwave-assisted synthesis of N-sulfonylaziridines
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A novel and efficient microwave-assisted one-step reaction was developed to synthesize chiral N-sulfonylaziridines by the reaction of different chiral amino alcohols and sulfonic chlorides. The newly developed microwave synthetic method has the advantage of reducing the reaction time from 24 to 0.5 h with improved yields (84-93%) and minimizing by-products.
- Xu, Hao,Tian, Hua,Zheng, Liangyu,Liu, Qingwen,Wang, Li,Zhang, Suoqin
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body text
p. 2873 - 2875
(2011/06/21)
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- The first synthesis of β-amino phosphonates using cyclic sulfamidates
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Cyclic sulfamidates (prepared from α-amino acids and β-amino alcohols) have been used for the first time for the synthesis of novel β-amino phosphonates (chiral and achiral) by treatment with dialkyl phosphites using sodium hydride. 2-Substituted and 1,2-disubtituted β-amino phosphonates have efficiently been prepared following this method. The products are formed in high yield (79-84%) within 8-12 h.
- Das, Biswanath,Reddy, Cheruku Ravindra,Nagendra, Siddavatam,Lingaiah, Maram
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scheme or table
p. 3496 - 3498
(2011/07/08)
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- Three mechanisms of asymmetric polymerization of phenylacetylenes having an l-amino ether residue and two hydroxy groups
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Three novel chiral phenylacetylenes having an octyloxyethanolamine residue derived from a l-aminoalcohol and two hydroxymethyl groups were synthesized and polymerized by two achiral catalysts ((nbd) Rh+[I?6-(C6H5)B -(C6H5)3] and [Rh(nbd)Cl] 2/triethylamine (TEA)) and a chiral catalytic system ([Rh(nbd)Cl]2/(S)- or (R)-phenylethylamine ((S)- or (R)-PEA)). All of the resulting polymers showed Cotton effects at wavelengths around 430 nm. This observation indicated that they had an excess of one-handed helical backbones. Positive and negative Cotton effects were observed for the polymers having an l-valinol residue produced by using (S)- and (R)-PEA as a cocatalyst, respectively, although the monomers had the same chirality. The two polymers having an l-alaninol or l-phenylalaninol residues obtained by using (S)- and (R)-PEA as a cocatalyst showed CD absorptions with identical signs. Therefore, we found that the chiral monomer having an l-valinol residue was suitable for both modes of asymmetric polymerization, that is, helix-sense-selective polymerization (HSSP) with the chiral catalytic system and asymmetric-induced polymerization (AIP) with the achiral catalysts. However, the other two monomers having an l-alaninol or l-phenylalaninol residue were not suitable for HSSP because the helix sense could not be controlled by the chirality of PEA. To explain the unexpected behaviors in the asymmetric polymerizations of the two chiral monomers having a chiral bidentate ligand, a novel third mechanism of asymmetric polymerization, that is, self-helix-sense-selective polymerization (SHSSP), is proposed in this Article. This Article discusses the contribution of the three mechanisms (AIP, HSSP, and SHSSP) in asymmetric polymerizations of the three monomers.
- Jia, Hongge,Teraguchi, Masahiro,Aoki, Toshiki,Abe, Yunosuke,Kaneko, Takashi,Hadano, Shingo,Namikoshi, Takeshi,Ohishi, Tomoyuki
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experimental part
p. 8353 - 8362
(2011/11/12)
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- Total synthesis of the N,C-coupled naphthylisoquinoline alkaloids ancistrocladinium A and B and related analogues
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The N,C-coupled naphthyldihydroisoquinoline alkaloids ancistrocladinium A (3) and B (4), which possess an unprecedented iminium-aryl axis and show high in vitro antileishmanial activities, have been synthesized via a short sequence of eight linear steps, without the need of protecting groups. Key steps were a Buchwald-Hartwig amination and a Bischler-Napieralski cyclization, preferentially leading to the naturally predominant M-atropo-diastereomer in the case of 3, while the N,C-axis is configurationally semistable in 4. The highly convergent first access to this type of alkaloids will now facilitate the preparation of structural analogues for structure-activity relationship studies. Its general applicability was shown by the preparation of the sterically even more congested, as yet unnatural N,3′- and N,1′-coupled analogues, ancistrocladinium C (5) and D (6).
- Bringmann, Gerhard,Gulder, Tanja,Hertlein, Barbara,Hemberger, Yasmin,Meyer, Frank
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scheme or table
p. 1151 - 1158
(2010/04/01)
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- The enantioselective intramolecular Morita-Baylis-Hillman reaction catalyzed by amino acid-derived phosphinothiourea
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A series of chiral bifunctional phosphinothioureas derived from l-amino acids have been developed to promote the enantioselective intramolecular Morita-Baylis-Hillman reaction. The process afforded the cyclic hydroxyl enones with up to 84% ee and good yields under mild conditions.
- Gong, Jing-Jing,Yuan, Kui,Song, Hong-Liang,Wu, Xin-Yan
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scheme or table
p. 2439 - 2443
(2010/06/12)
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- Addition of allylzinc to a-amino acid-derived imines: Synthesis of diamino alcohols by Hydroboration
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Imines obtained by condensation of Z-pro- tected or Boc-protected α-amino aldehydes with α-amino tert-butyl esters or with O-silyl-protected amino alcohols were reacted with preformed allyl zinc yielding homoal- lylamines with yields around 50% and selectivities ranging from 50:50 to 90:10. Hydroboration of the terminal double bond furnished diamino alcohols with yields up to 97%. The configuration of the substrates was determined by X-ray-crystallographic analysis of a hydroboration product and comparison of physical data. Springer-Verlag 2010.
- Virlouvet, Mickael,Goesmann, Helmut,Feldmann, Claus,Podlech, Joachim
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experimental part
p. 177 - 198
(2010/08/05)
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- Simply air: Vanadium-catalyzed oxidative kinetic resolution of methyl o-chloromandelate by ambient air
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Vanadium-catalyzed oxidative kinetic resolution (OKR) of methyl o-chloromandelate 2a, key intermediate of the well-known oral antiplatelet agent (S)-clopidogrel, was achieved by ambient air for the first time. The air oxidation system, which was composed of vanadium and tridentate Schiff base ligands derived from amino alcohols and salicylaldehyde derivatives, afforded an efficient and economic approach to the target intermediate with high enantioselectivities (>99% ee).
- Yin, Lu,Jia, Xian,Li, Xing Shu,Chan, Albert S.C.
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body text
p. 774 - 777
(2011/11/12)
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- COMPOSITIONS AND METHODS FOR CYCLOFRUCTANS AS SEPARATION AGENTS
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The present invention relates to derivatized cyclofructan compounds, compositions comprising derivatized cyclofructan compounds, and methods of using compositions comprising derivatized cyclofructan compounds for chromatographic separations of chemical species, including enantiomers. Said compositions may comprise a solid support and/or polymers comprising derivatized cyclofructan compounds.
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Page/Page column 45-49; 59
(2010/12/31)
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- PROCESS FOR THE PREPARATION OF (S)-2-AMINO-1-PROPANOL (L-ALANINOL) FROM (S)-1-METHOXY-2-PROPYLAMINE
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The invention relates to a process for the preparation of (S)-2-amino-1-propanol (L-alaminol) from (S)-1-methoxy-2-propylamine via the hydrochloride of (S)-2-amino-1-propanol and subsequent work-up.
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Page/Page column 4
(2010/10/03)
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- Synthesis of novel N-protected β3-amino nitriles: study of their hydrolysis involving a nitrilase-catalyzed step
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Several commercially available nitrilases were investigated with regard to their potential to hydrolyze N-protected β3-amino nitriles into their corresponding N-protected β3-amino acids. The biotransformations were obtained in different proportions depending on the nitrilase involved. The best hydrolysis results were achieved for the N-Cbz-β3-amino nitrile from l-alanine using the NIT-107, in a phosphate buffer at 0.05 M. However, no biotransformation into the corresponding acids was observed for the N-sulfonylamide β3-amino nitriles. Two simple and efficient procedures to prepare the β3-amino nitriles from their analogous α-amino acids are described. Thirty four new substances were synthesized and characterized over the course of this work.
- Veitia, Maite Sylla-Iyarreta,Brun, Pierre Louis,Jorda, Pierre,Falguieres, Annie,Ferroud, Clotilde
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scheme or table
p. 2077 - 2089
(2010/03/04)
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- Syntheis of new chiral 5,6,7,8-tetrahydrotetrazolo[1,5-a]pyrazines from α-amino acid derivatives following "click" chemistry
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An efficient and practical synthesis of new chiral fused tetrazoles have been synthesized following [3+2] cycloaddition reaction starting from α-amino acid derivatives.
- Mohapatra, Debendra K.,Maity, Pradip K.,Ghorpade, Ravindra V.,Gurjar, Mukund K.
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body text
p. 865 - 872
(2010/09/16)
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- METHOD FOR FRACTIONATING STEREOISOMERIC COMPOUNDS
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The present invention relates to a method for fractionating stereoisomeric compounds which have at least one alcohol and/or amino group.
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Page/Page column 11
(2009/02/11)
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- Synthesis of chiral polydentate ligands and the use of their titanium complexes as pre-catalysts for the asymmetric trimethylsilylcyanation of benzaldehyde
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A number of polydentate ligands based on enantiomerically pure binaphthol have been synthesized. The ligand complexes with titanium isopropoxide were used as catalysts for the asymmetric addition of trimethylsilyl cyanide to benzaldehyde. A fragment with axial chirality is responsible for the configuration of O-trimethylsilyl cyanohydrin product. In the case of the optimum ligand based on (R)-binaphthol and (S)-leucinol, an enantiomeric excess of 86% and quantitative yield were achieved in 4 h.
- Belokon,Chusov,Skrupskaya,Bor'Kin,Yashkina,Lyssenko,Il'In,Strelkova,Timofeeva,Peregudov,North
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experimental part
p. 1981 - 1988
(2009/12/23)
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- Prevention and treatment of cardiac conditions
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The present invention provides a method of treating conditions associated with iron and calcium overload comprising administering an effective amount of dexrazoxane or a non-dexrazoxane compound of formula (IA), (IB), or (IC) or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof.
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Page/Page column 21
(2008/12/08)
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- Forward- and reverse-synthesis of piperazinopiperidine amide analogs: A general access to structurally diverse 4-piperazinopiperidine-based CCR5 antagonists
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Piperazinopiperidine amide analogs are among the most promising CCR5 antagonists. As an effective extension of a previously-reported methodology to synthesize such compounds, forward- and reverse-syntheses were successfully developed in which the convergent synthesis of the piperazinopiperidine nucleus, with a building block of 4-substituent-4-aminopiperidine, served as a common key step. The two-way approach affords a comprehensive access to the piperazinopiperidine templated library with variation on the pharmacophore sites. Thus, a SAR study of our synthesized piperazinopiperidine-based CCR5 antagonists was conducted with respect to the structure and configuration of the substituent on the piperazine ring. The S-configuration of the benzylic-substituent is vital for the CCR5 binding, and the bulky or aryl substituent on the 2-position in the piperazine ring is detrimental to the activity. By using the forward-synthesis approach, the best compound in the chiral piperazine-based CCR5 antagonist series, Sch-D (Vicriviroc), was conveniently synthesized in an excellent yield. The Royal Society of Chemistry.
- Feng, Dong-Zhi,Song, Yan-Li,Jiang, Xiao-Hua,Chen, Li,Long, Ya-Qiu
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p. 2690 - 2697
(2008/03/12)
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- A convenient synthetic route to enantiopure N-tosylazetidines from α-amino acids
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A general and convenient synthetic route to various chiral 2-substituted- and 2,4-disubstituted-N-tosylazetidines (ee >99%) is described in good overall yields starting from chiral α-amino acids using very simple chemistry.
- Ghorai, Manas K.,Das, Kalpataru,Kumar, Amit
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p. 2471 - 2475
(2007/10/03)
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- A new approach towards peptidosulfonamides: synthesis of potential inhibitors of bacterial peptidoglycan biosynthesis enzymes MurD and MurE
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Peptidosulfonamides are an emerging group of peptidomimetics with a variety of applications in medicinal chemistry. We present a novel approach to the synthesis of peptidosulfonamides, and apply it to a series of new potential inhibitors of the bacterial peptidoglycan biosynthesis enzymes MurD and MurE. The synthesis was conducted via N-phthalimido β-aminoethanesulfonyl chlorides, which are new building blocks for the synthesis of peptidosulfonamides. In the most crucial step, sulfonic acids or their sodium salts were converted into the corresponding sulfonyl chlorides using an excess of either SOCl2 or SOCl2/DMF, and then coupled to the C-protected amino acid. None of the compounds significantly inhibited MurD, however, some inhibited MurE; one had an IC50 below 200 μM, which constitutes a promising starting point for further development. Molecular modelling simulations were performed on two analogues to investigate the absence of inhibitory activity of the sulfonamide compounds on MurD.
- Humljan, Jan,Kotnik, Miha,Boniface, Audrey,?olmajer, Toma?,Urleb, Uro?,Blanot, Didier,Gobec, Stanislav
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p. 10980 - 10988
(2007/10/03)
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- Synthesis and properties of novel chiral-amine-functionalized ionic liquids
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A novel class of chiral-amine-functionalized ionic liquids (CAFILs) has been synthesized efficiently from natural amino acids, and their structures have been determined by spectroscopic analysis and low temperature X-ray diffraction analysis. The CAFILs have been characterized by physical properties such as melting point, glass transition temperature, thermal degradation and specific rotation. NMR measurements indicate that the CAFILs may be promising alternatives in the field of chiral discrimination.
- Luo, Shu-Ping,Xu, Dan-Qian,Yue, Hua-Dong,Wang, Li-Ping,Yang, Wen-Long,Xu, Zhen-Yuan
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p. 2028 - 2033
(2007/10/03)
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- Synthesis of N-phthalimido β-aminoethanesulfonyl chlorides: The use of thionyl chloride for a simple and efficient synthesis of new peptidosulfonamide building blocks
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N-Phthalimido β-aminoethanesulfonyl chlorides, new building blocks for the synthesis of peptidosulfonamide peptidomimetics, were prepared in a straightforward manner from amino acids. In the crucial synthetic step, sulfonic acids or their sodium salts were converted into the corresponding sulfonyl chlorides using an excess of refluxing thionyl chloride or thionyl chloride/DMF. This simple and effective chlorinating method is also applicable to β-aminoethane sulfonic acids and their sodium salts with other N-protecting groups.
- Humljan, Jan,Gobec, Stanislav
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p. 4069 - 4072
(2007/10/03)
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- New pyrrole-based amino acids for the synthesis of peptidomimetic constrained scaffolds
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A new family of pyrrole-based amino acids have been prepared through the microwave assisted Paal-Knorr reaction of 1-4 ketoesters derived from the corresponding β-ketoester with a functional homologation. The carboxylic group is located in position 3 of the pyrrole, whereas the amino group, protected with the Cbz moiety, is present on the side chain in positions 1 or 2. These compounds were used to prepare constrained oligopeptides.
- Alongi, Maddalena,Minetto, Giacomo,Taddei, Maurizio
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p. 7069 - 7072
(2007/10/03)
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