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C-2 Position (c-2 + position)
Selected AbstractsChemInform Abstract: Synthesis of Fused Thiopyranthione and Thiophene Derivatives from 4,5-Dihydro-3-thiophene(and -3-furan)-carbonitriles Having an Active Methylene Group at C-2 Position.CHEMINFORM, Issue 33 2010Hiroshi Maruoka Abstract The title carbonitriles (III) are readily converted into novel fused thiopyranthione (V) and thiophene derivatives (VI). [source] Regioselective C-2 or C-5 Direct Arylation of Pyrroles with Aryl Bromides using a Ligand-Free Palladium CatalystADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 11-12 2009Julien Roger Abstract A simple and atom-economical procedure for the regioselective C-2 or C-5 arylation of pyrroles via a CH bond activation is reported. Only 0.5,0.01 mol% of commercially available and air-stable ligand-free palladium(II) acetate [Pd(OAc)2] was employed as the catalyst. The presence of electron-withdrawing substituents such as formyl, acetyl or ester at the C-2 position of the pyrrole is tolerated. This environmentally attractive procedure has also been found to be tolerant to a very wide variety of functional groups on the aryl bromides such as formyl, acetyl, propionyl, ester, nitrile, nitro, fluoro, methoxy, amino or trifluoromethyl. [source] Synthesis and deuterium labelling of the pure selective estrogen receptor modulator (SERM) acolbifene glucuronidesJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 3 2007Jean-Yves Sancéau Abstract Acolbifene (EM-652·HCl, SCH 57068·HCl), a highly potent and orally active selective estrogen receptor modulator (SERM), is at late stage clinical development for the treatment of estrogen-sensitive breast cancer. Acolbifene-7-glucuronide 1 (major) and acolbifene-4,-glucuronide 2 (minor) were identified as metabolites of acolbifene in the human. The two monoglucuronides and a diglucuronide 3 as well as the corresponding 2H-labelled derivatives 4,6 were synthesised for use as preclinical and clinical standards for LC,MS/MS analysis. All glucuronides were prepared by the Schmidt glycosylation of monoprotected acolbifene with a glucuronyl imidate at ,10°C to prevent epimerisation at the C-2 position. The two monoglucuronides 1 and 2 of acolbifene were separated by semi-preparative HPLC. Incorporation of three deuteriums was achieved by alkylation of chromanone 15 with C2H3MgI followed by dehydration with C2H3CO22H/2H2O. After chemical resolution and salt neutralisation, [2H3]acolbifene 19 was obtained with 99.4% enantiomeric purity and >98% isotopic purity. Copyright © 2007 John Wiley & Sons, Ltd. [source] Synthesis and herbicidal activity of phenyl-substituted benzoylpyrazolesPEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 12 2002Thomas L Siddall Abstract A novel series of substituted 3-phenyl benzoylpyrazoles were prepared and tested as potential grass herbicides. The targeted materials were prepared by three newly developed synthetic routes, which allowed a comprehensive study of the SAR (structure,activity relationships) of this series. The best combination of grass weed activity (Avena fatua L, Setaria viridis (L) Beauv and Alopecurus myosuroides Huds) and wheat selectivity was obtained with an alkoxy group in the 4-position of the phenyl ring. Activity was further enhanced by the presence of tert -butyl on the pyrazole and a methyl group at the C-2 position of the benzoyl moiety. The alkoxy-substituted 3-phenylbenzoylpyrazoles are a novel class of herbicides with potential utility for control of important grass weeds in cereals. © 2002 Society of Chemical Industry [source] Characterization of New PPAR, Agonists: Analysis of Telmisartan's Structural ComponentsCHEMMEDCHEM, Issue 3 2009Matthias Goebel Abstract Telmisartan was originally designed as an AT1 antagonist but was later also characterized as a selective PPAR, modulator. This study focused on the identification of the essential structural motifs of telmisartan for PPAR, activation activity, elucidating the individual SAR of each different component (shown). In addition to a proven efficacy in lowering blood pressure, the AT1 receptor blocker telmisartan has recently been shown to exert pleiotropic effects as a partial agonist of the nuclear peroxisome proliferator-activated receptor gamma (PPAR,). Based on these findings and an excellent side-effect profile, telmisartan may serve as a lead structure for the development of new PPAR, ligands. Therefore, we analyzed the structural components of telmisartan to identify those necessary for PPAR, activation. Synthesized compounds were tested in a differentiation assay using 3T3-L1 preadipocytes and a luciferase assay with COS-7 cells transiently transfected with pGal4-hPPAR,DEF, pGal5-TK-pGL3 and pRL-CMV. The data obtained in this structure,activity relationship (SAR) study provide the basis for the development of new PPAR, ligands, which could lead to active compounds with a distinct, beneficial pharmacological profile compared with the existing full agonists. The basic 1-(biphenyl-4-ylmethyl)-1H -benzimidazole scaffold of telmisartan was identified as an essential moiety with either a carboxylic acid or tetrazole group at the C-2 position of the biphenyl. For maximum potency and activity, the alkyl chain in position 2 requires a minimum length of at least two C atoms (ethyl group), while the methyl group at position 4 of the benzimidazole core seems to contribute to partial activity. An additional benzimidazole at position 6 appears to be a further determinant of potency. Similar conclusions can be drawn for the methyl group in position 1. [source] Exploring the Biocatalytic Scope of Alditol Oxidase from Streptomyces coelicolorADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 10 2009W. van Hellemond Abstract The substrate scope of the flavoprotein alditol oxidase (AldO) from Streptomyces coelicolor A3(2), recombinantly produced in Escherichia coli, was explored. While it has been established that AldO efficiently oxidizes alditols to D -aldoses, this study revealed that the enzyme is also active with a broad range of aliphatic and aromatic alcohols. Alcohols containing hydroxy groups at the C-1 and C-2 positions like 1,2,4-butanetriol (Km=170,mM, kcat=4.4,s,1), 1,2-pentanediol (Km=52,mM, kcat=0.85,s,1) and 1,2-hexanediol (Km=97,mM, kcat=2.0,s,1) were readily accepted by AldO. Furthermore, the enzyme was highly enantioselective for the oxidation of 1,2-diols [e.g., for 1-phenyl-1,2-ethanediol the (R)-enantiomer was preferred with an E -value of 74]. For several diols the oxidation products were determined by GC-MS and NMR. Interestingly, for all tested 1,2-diols the products were found to be the ,-hydroxy acids instead of the expected ,-hydroxy aldehydes. Incubation of (R)-1-phenyl-1,2-ethanediol with 18O-labelled water (H218O) revealed that a second enzymatic oxidation step occurs via the hydrate product intermediate. The relaxed substrate specificity, excellent enantioselectivity, and independence of coenzymes make AldO an attractive enzyme for the preparation of optically pure 1,2-diols and ,-hydroxy acids. [source] Bioconversion of 3,-acetoxypregna-5,16-diene-20-one to androsta-1,4-diene-3,17-dione by mixed bacterial cultureLETTERS IN APPLIED MICROBIOLOGY, Issue 2 2002S. Patil Aims:,To isolate a bacterium capable of degrading 3,-acetoxypregna-5,16-diene-20-one (16-DPA) to androsta-1,4-diene-3,17-dione (ADD) and to decipher the biodegradation pathway. Methods and Results:,Isolation on mineral salt agar containing 16-DPA as sole carbon source yielded two bacteria identified as Pseudomonas diminuta and Comamonas acidovorons. These bacteria failed to degrade 16-DPA individually in pure cultures but converted 16-DPA to ADD in a mixed culture. The intermediates accumulated during the bioconversion were identified as pregna-4,16-diene-3,20-dione and pregna-1,4,16-triene-3,20-dione. Conclusions:,The degradation pattern of 16-DPA by mixed bacterial culture revealed the reaction sequence as (i) cleavage of C-3 acetyl function, (ii) dehydrogenation at C-1 and C-2 positions and (iii) cleavage of C-17 side-chain. Significance and Impact of the Study:,The present work opens a new approach towards the production of a female sex hormone precursor and elucidates the biodegradation pathway of 16-DPA by mixed bacterial culture. [source] | ||||||||||