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Synthetic Intermediates (synthetic + intermediate)
Selected AbstractsChemoenzymatic Route to Both Enantiomers of a 1-Isopropyl-3a-methyloctahydroinden-4-one Derivative: A Synthetic Intermediate for Sesqui- and DiterpenoidsADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 7-8 2005Shigeo Fujieda Abstract On the way to a chemoenzymatic synthesis of a key intermediate for sesquiterpenoids and diterpenoids, 2-methyl-2-(4-methyl-3-oxopentyl)-1,3-cyclohexanedione was reduced with the whole cells of yeast biocatalysts. Torulaspora delbrueckii NBRC10921 reduced a cyclic ketone of three carbonyl groups in an enantiofacially selective manner (re -face attack), but there was poor enantiotopic group selectivity between two carbonyl groups on the cyclohexane ring to yield a mixture of diastereomeric products. Candida floricola IAM13115 reduced mainly the pro -(R) carbonyl group. In contrast, the reduction proceeded in an enantiofacially poorly selective manner to give another set of diastereomeric products. In both cases, another carbonyl group on the side chain worked as a ,trapping arm' of the resulting secondary alcohol. The diastereomeric products were effectively separated as the ,syn' or ,cis' isomer exclusively exist in the intramolecular hemiacetal structure, while ,anti' or ,trans' isomer being an equilibrated mixture of cyclic hemiacetal and open-chain hydroxyketone (ca. 0.7,:,1). Starting separately from the enantiomerically enriched products as above, both enantiomers of the target compound, a key intermediate for terpenoids, were efficiently prepared via stereoselective ring closure under pinacol coupling reaction conditions. Furthermore, a daucane sesquiterpene intermediate, a hydroazulene derivative, was provided after one-carbon homologation of the six-membered ring. [source] ChemInform Abstract: A Facile Synthesis of Fluorine-Containing Heterocycles , Use of 1,1,1-Trifluoro-2-alkanones as a Convenient Synthetic Intermediate.CHEMINFORM, Issue 44 2001Yasuhiro Kamitori Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] Synthesis and Properties of Oligodeoxynucleotide Analogs with Bis(methylene) Sulfone BridgesHELVETICA CHIMICA ACTA, Issue 9 2003Bernd Eschgfäller A convergent, solution-phase synthesis was developed for the bis(methylene) sulfone-bridged oligodeoxynucleotide analogs (SNA) 5,-d(HOCH2 -Tso2Tso2Tso2Cso2Tso2Tso2Tso2T-CH2SO)-3, (35b) and 5,-d(HOCH2 -Tso2Tso2Tso2Tso2Tso2Tso2Tso2T-CH2SO)-3, (34c) (SO2 corresponds to CH2SO2CH2 instead of OP(O)(O,)(O). In these, the phosphodiester linkages are replaced by non-ionic bis(methylene) sulfone linkers. The general strategy involved convergent coupling of 3,,5,-bishomo- , - D -deoxyribonucleotide analogs functionalized at the 6,-end (CH2C(5,)) as bromides or mesylates and at the CH2C(3,) position as thiols, with the resulting thioether being oxidized to the corresponding sulfone. A single charge was introduced at the terminal CH2C(3,) position of the octamers to increase their solubility in water. During the synthesis, it became apparent that the key intermediates generated secondary structures through either folding or aggregation in a variety of solvents. This generated unusual reactivity and was unique for very similar structures. For example, although the dimeric thiol d(BzOCH2 -Tso2C-CH2SH) (14b) was a well-behaved synthetic intermediate, the tetrameric thiol d(TrOCH2 -Tso2Tso2Tso2toC-CH2SH) derived from the corresponding thioacetate was rapidly converted to a disulfide by very small amounts of oxidant (28,29, Scheme,6), while the analogous tetrameric thiol d(BzOCH2 -Tso2TsTso2T-CH2SH) (26), differing only by a single heterocycle, was oxidized much more slowly (Bz=PhCO, Tr=Ph3C, to=2-MeC6H4CO (at N4 of dc)). The sequence-dependent reactivity, well known in many classes of natural products (including polypeptides), is not prominent in natural oligonucleotides. These results are discussed in light of the proposal that the repeating negative charge in nucleic acids is key to their ability to serve as genetic molecules, in particular, their capability to support Darwinian evolution. The ability of 5,-d(HOCH2 -Tso2Tso2Tso2Cso2Tso2Tso2Tso2T-CH2SO)-3, (35b) to bind as a third strand to duplex DNA was also examined. No triple-helix-forming propensity was detected in this molecule. [source] Synthesis of Scopin Acetate and 6,7-Didehydrohyoscyamin.HELVETICA CHIMICA ACTA, Issue 9 2003Intramolecular Phenylsulfenylation of a Nonactivated Methylene Group of Ethyl N -Demethyl-3- O -(phenylthio)tropine- N -carboxylate The synthesis of scopin acetate (6b) and 6,7-didehydrohyoscyamine (17) was achieved by using tropine (5) as the starting compound. Formal (phenylthio)-radical transfer to the nonactivated 6-position of ethyl N -demethyl-3- O -(phenylthio)tropine- N -carboxylate (9) by irradiation in the presence of hexabutyldistannane is a key step of this synthetic approach, involving ethyl 6,7-didehydro- N -demethyltropine- N -carboxylate (15) as a synthetic intermediate (Schemes,3 and 5). The reaction of 9 with tributylstannane in the presence of ethyl acrylate, as a radicophilic olefin, involves Michael -type alkylation at C(6) of the tropine skeleton affording ethyl N -demethyl- N -(ethoxycarbonyl)tropine-6-propanoate (18) (Scheme,6). [source] An Efficient Total Synthesis of Optically Active Tetrodotoxin,from,LevoglucosenoneCHEMISTRY - AN ASIAN JOURNAL, Issue 1-2 2006Daisuke Urabe Abstract Tetrodotoxin, a toxic principal of puffer-fish poisoning, is one of the most famous marine natural products, and has been known as a formidable synthetic target in synthesis owing to its multifunctional structure and unusual chemical properties. From the perspective of supplying tetrodotoxin derivatives such as labeled molecules for biochemical research, we have completed our second total synthesis of tetrodotoxin from a synthetic intermediate for 11-deoxytetrodotoxin, which was previously prepared from levoglucosenone as a chiral starting material in this laboratory. This paper discloses the details of the total synthesis with special reference to significant influences on the neighboring functional groups found in the installation of guanidine. The established route should allow us to prepare the tetrodotoxin-related compounds required for biochemical studies. [source] Alkoxy-5-nitrosopyrimidines: Useful Building Block for the Generation of Biologically Active CompoundsEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 20 2010Antonio Marchal Abstract Several alkoxy-5-nitrosopyrimidines were synthesised and high regioselective and sequential nucleophilic aromatic substitution of methoxy groups in 2-amino-4,6-dimethoxy-5-nitrosopyrimidine was observed. The approach was applied to the synthesis of valuable polyfunctionalised aminopyrimidines capable of mimicking fused heterobicyclic derivatives of biological interest. In addition, new compounds were evaluated as antivirals and their usefulness as synthetic intermediates was demonstrated. [source] Regioselective Mo-Catalyzed Hydrostannations as Key Steps in the Synthesis of Functionalized Amino Alcohols and Heterocycles,EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 17 2007Hechun Lin Abstract Molybdenum catalyzed hydrostannation of suitable protected propargylic amino alcohols provides the corresponding functionalized vinyl stannanes, which are useful synthetic intermediates for the combinatorial synthesis of amino alcohols and heterocycles. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source] Conformationally Biased Selective Alkylation of trans -Cyclohexane-1,2-bis(sulfonamide) Assisted by Solvent-Tuned Protecting Groups: Applications to the Synthesis of a Large Optically Active Polyazamacrocycle,EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 17 2006Carmen Peña Abstract The selective alkylation of (R,R)-cyclohexane-1,2-bis(sulfonamide) with trityl bromoalkyl ethers has been studied in detail. The major formation of either mono- or dialkylated compounds clearly depends on the right combination of protecting groups and the reaction solvent. An exhaustive study suggests that this effect can be reasonably explained by the conformational preferences of the monoalkylated compounds, which also depend on the reaction medium, solvophobic effects and weak intramolecular interactions. Structural analysis by NOE measurements showed the presence of folded conformations in solution for all the tested examples. Monte Carlo conformational searches supported this proposal, showing a very good correlation between the fraction of folded species and the selectivity towards monoalkylation. Finally, tuning of the reaction conditions, leading to either extended or folded conformations of the monoalkylated synthetic intermediates, was exploited for the efficient synthesis of a large optically active polyazamacrocycle. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) [source] Identification of stemonamide synthetic intermediates as a novel potent anticancer drug with an apoptosis-inducing abilityINTERNATIONAL JOURNAL OF CANCER, Issue 2 2010Ying-Yi Li Abstract We previously demonstrated that Pim-3, a protooncogene with serine/threonine kinase activity, was aberrantly expressed in malignant lesions but not in normal tissues of endoderm-derived organs, including pancreas, liver, colon and stomach. Moreover, aberrantly expressed Pim-3 can prevent tumor cell apoptosis by inactivating a proapoptotic molecule, Bad, and enhancing the expression of an antiapoptotic molecule, Bcl-XL. These observations prompted us to speculate that a chemical targeting Pim-3 kinase may be a good candidate for a novel type of anticancer drug. Hence, we screened various low-molecule compounds by examining their capacity to inhibit Pim-3 kinase activity in vitro. We observed that some synthetic intermediates of stemonamide can inhibit in vitro activities of Pim-3 kinase and its related kinases, such as Pim-1 and Pim-2. Moreover, these compounds inhibit in vitro cell proliferation of various human pancreatic, hepatocellular and colon cancer cell lines. Furthermore, the compounds can induce apoptosis of human pancreatic cancer cell lines in vitro by reducing the amount of phospho-Ser112 -Bad, but not total amounts of Bad and Pim-3. Finally, when the compound was administered to nude mice injected with a human pancreatic cancer cell line, it retarded tumor growth by increasing apoptotic cell numbers and decreasing proliferating cell numbers without causing serious adverse effects on blood counts. These observations indicate that the chemicals and its related compounds may be effective for the treatment of tumors of endoderm-derived organs, particularly the pancreas. [source] Structure elucidation and reaction monitoring of synthetic intermediates using an automated accurate mass GC-TOF mass spectrometer in drug discoveryJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 10 2005Chris Petucci [source] Stability studies of oxazolidine-based compounds using 1H NMR spectroscopyJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 8 2010Gerard P. Moloney Abstract A series of oxazolidine-based compounds with a variety of substituents in positions 2 and 3 was synthesized and their stability studied. Ring opened intermediates formed on addition of limiting amounts of D2O to oxazolidine solutions, as observed by NMR. As the hydrolysis reactions proceeded, a series of novel dimeric ,-amino alcohol compounds formed via an internal reaction between ephedrine and the ring opened intermediates. 2-Phenyl substituted oxazolidine compounds containing electron withdrawing nitro substituents were more rapidly hydrolyzed than the unsubstituted derivative and methoxy substituted compounds, with the nitro substituents appearing to stabilize the ring opened intermediates. Two oxazolidine derivatives, with a methyl and proton at position 2, were found to be more stable to oxazolidine hydrolysis than the 2-phenyl substituted compounds. Oxazolidines incorporating phenyl substituents at position 3 were synthesized and found to be less stable than those incorporating a methyl substituent at position 3. These fundamental structure,activity relationships may be useful when choosing oxazolidine derivatives as synthetic intermediates and as prodrugs for the delivery of compounds containing either ,-amino alcohol or aldehyde components. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:3362,3371, 2010 [source] Enaminones: Exploring additional therapeutic activitiesJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 10 2007Ivan O. Edafiogho Abstract Enaminones, enamines of ,-dicarbonyl compounds, have been known for many years. Their early use has been relegated to serving as synthetic intermediates in organic synthesis and of late, in pharmaceutical development. Recently, the therapeutic potential of these entities has been realized. This review provides the background and current research in this area with emphasis of these agents as potential anticonvulsants, their proposed mechanisms of action, and as potential modulators of multidrug resistance (MDR). © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 2509,2531, 2007 [source] Enantioselective HPLC resolution of synthetic intermediates of armodafinil and related substancesJOURNAL OF SEPARATION SCIENCE, JSS, Issue 6-7 2008Ramisetti Nageswara Rao Abstract Armodafinil is a unique psychostimulant recently approved by the US Food and Drug Administration for the treatment of narcolepsy. The chromatographic resolution of its chiral intermediates including related substances in the total synthesis of armodafinil was studied on polysaccharide-based stationary phases, viz. cellulose tris-(3,5-dimethylphenylcarbamate) (Chiralcel OD-H) and amylose tris-(3,5-dimethylphenylcarbamate) (Chiralpak AD-H) by HPLC. The effects of 1-propanol, 2-propanol, ethanol, and trifluoroacetic acid added to the mobile phase and of column temperature on resolution were studied. A good separation was achieved on cellulose-based Chiralcel OD-H column compared to amylose-based Chiralpak AD-H. The effects of structural features of the solutes and solvents on discrimination between the enantiomers were examined. Baseline separation with Rs >1.38 was obtained using a mobile phase containing n -hexane,ethanol,TFA (75:25:0.15 v/v/v). Detection was carried out at 225 nm with photodiode array detector while identification of enantiomers was accomplished by a polarimetric detector connected in series. The method was found to be suitable not only for process development of armodafinil but also for determination of the enantiomeric purity of bulk drugs and pharmaceuticals. [source] Analysis of triacetone triperoxide (TATP) and TATP synthetic intermediates by electrospray ionization mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 2 2008Michael E. Sigman The explosive triacetone triperoxide (TATP) has been analyzed by electrospray ionization mass spectrometry (ESI-MS) on a linear quadrupole instrument, giving a 62.5,ng limit of detection in full scan positive ion mode. In the ESI interface with no applied fragmentor voltage the m/z 245 [TATP,+,Na]+ ion was observed along with m/z 215 [TATP,+,Na , C2H6]+ and 81 [(CH3)2CO,+,Na]+. When TATP was ionized by ESI with an applied fragmentor voltage of 75,V, ions at m/z 141 [C4H6O4,+,Na]+ and 172 [C5H9O5,+,Na]+ were also observed. When the precipitates formed in the synthesis of TATP were analyzed before the reaction was complete, a new series of ions was observed in which the ions were separated by 74,m/z units, with ions occurring at m/z 205, 279, 353, 427, 501, 575, 649 and 723. The series of evenly spaced ions is accounted for as oligomeric acetone carbonyl oxides terminated as hydroperoxides, [HOOC(CH3)2{OOC(CH3)2}nOOH,+,Na]+ (n,=,1, 2,,,8). The ESI-MS spectra for this homologous series of oligoperoxides have previously been observed from the ozonolysis of tetramethylethylene at low temperatures. Precipitates from the incomplete reaction mixture, under an applied fragmentor voltage of 100,V in ESI, produced an additional ion observed at m/z 99 [C2H4O3,+,Na]+, and a set of ions separated by 74,m/z units occurring at m/z 173, 247, 321, 395, 469 and 543, proposed to correspond to [CH3CO{OOC(CH3)2}nOOH,+,Na]+ (n,=,1,2,,,5). Support for the assigned structures was obtained through the analysis of both protiated and perdeuterated TATP samples. Copyright © 2007 John Wiley & Sons, Ltd. [source] Cell line-specific control of recombinant monoclonal antibody production by CHO cells,BIOTECHNOLOGY & BIOENGINEERING, Issue 6 2010Peter M. O'Callaghan Abstract In this study we compare the cellular control of recombinant human IgG4 monoclonal antibody (Mab) synthesis in different CHO cell lines. Based on comprehensive empirical analyses of mRNA and polypeptide synthetic intermediates we constructed cell line-specific mathematical models of recombinant Mab manufacture in seven GS-CHO cell lines varying in specific production rate (qMab) over 350-fold. This comparative analysis revealed that control of qMab involved both genetic construct and cell line-specific factors. With respect to the former, all cell lines exhibited excess production of light chain (LC) mRNA and polypeptide relative to heavy chain (HC) mediated by more rapid LC transcription and enhanced LC mRNA stability. Downstream of this, cell lines differed markedly in their relative rates of recombinant mRNA translation, Mab assembly and secretion although HC mRNA abundance and the rate of HC translation generally exerted most control over qMab,the latter being directly proportional to qMab. This study shows that (i) cell lines capable of high qMab exceed a threshold functional competency in all synthetic processes, (ii) the majority of cells in parental and transfected cell populations are functionally limited and (iii) cell engineering strategies to increase Mab production should be cell line specific. Biotechnol. Bioeng. 2010;106: 938,951. © 2010 Wiley Periodicals, Inc. [source] Total Synthesis, Characterization, and Conformational Analysis of the Naturally Occurring Hexadecapeptide Integramide,A and a DiastereomerCHEMISTRY - A EUROPEAN JOURNAL, Issue 1 2010Marta De, Zotti Dr. Abstract Integramide,A is a 16-amino acid peptide inhibitor of the enzyme HIV-1 integrase. We have recently reported that the absolute stereochemistries of the dipeptide sequence near the C terminus are L -Iva14 - D -Iva15. Herein, we describe the syntheses of the natural compound and its D -Iva14 - L -Iva15 diastereomer, and the results of their chromatographic/mass spectrometric analyses. We present the conformational analysis of the two compounds and some of their synthetic intermediates of different main-chain length in the crystal state (by X-ray diffraction) and in solvents of different polarities (using circular dichroism, FTIR absorption, and 2D NMR techniques). These data shed light on the mechanism of inhibition of HIV-1 integrase, which is an important target for anti-HIV therapy. [source] Macrocyclic Hexaureas: Synthesis, Conformation, and Anion BindingCHEMISTRY - A EUROPEAN JOURNAL, Issue 19 2009Denys Meshcheryakov Dr. Abstract Varied flexibility: Cyclic oligoureas are formed by using anions as templates. Linking of six xanthene and/or diphenyl ether fragments by urea groups leads to the formation of five macrocyclic compounds with a 48-membered ring with variable flexibility (see picture). Their interaction with anions shows a strong influence of acetate and chloride ions on the cyclization from four precursor molecules. Five macrocylic compounds XXXXXX, XXDXXD, XDXDXD, XDDXDD, and DDDDDD with 48-membered rings, in which six xanthene and/or diphenyl ether fragments are linked through six urea (-NH-C(O)-NH-) groups, have been synthesized. In the cyclization step, a linear diamine was allowed to react with the appropriate diisocyanate by using a [5+1] (i.e., "XDXDX+D" for XDXDXD), [4+2] (DDDDDD), or [3+3] (XDDXDD) procedure. Compounds XXXXXX and XXDXXD were prepared from two molecules of the dimeric amine XX and two molecules of the respective monomeric diisocyanate (X or D) in a [2+1+2+1] (or 2×[2+1]) reaction. The (nonoptimized) yields in the cyclization step ranged from 45 to 80,%. The linear precursor diamines or diisocyanates were obtained by analogous condensation reactions by using partial protection with a tert -butoxycarbonyl group. All the macrocyclic compounds and synthetic intermediates were characterized by 1H,NMR and mass spectra. Three different crystal structures were obtained for XDDXDD, which show the molecule in a more or less strongly folded conformation determined by intramolecular hydrogen bonding. The interaction of the hexaureas with selected anions was studied by 1H,NMR spectroscopy and UV absorption spectrophotometry. [source] Neuroprotective Effects of N -Alkyl-1,2,4-oxadiazolidine-3,5-diones and Their Corresponding Synthetic Intermediates N -Alkylhydroxylamines and N -1-Alkyl-3-carbonyl-1-hydroxyureas against in,vitro Cerebral IschemiaCHEMMEDCHEM, Issue 1 2010Alain, Cesar Biraboneye Abstract Herein we report the synthesis and neuroprotective effects of new N -alkyl-1,2,4-oxadiazolidine-3,5-diones and their corresponding synthetic intermediates, N -alkylhydroxylamines and N -1-alkyl-3-carbonyl-1-hydroxyureas, in an in,vitro model of ischemia. We found five analogues that protect HT22 cells from death in the concentration range of 1,5,,M. Because members of the MAP kinase family are known to be key players in nerve cell survival and death, we characterized the role of these kinases in the neuroprotective mechanisms of the newly synthesized analogues. The results indicate that these compounds provide neuroprotection through distinct mechanisms of action. [source] Unlocking the Chemotherapeutic Potential of ,-Aminovinyl Ketones and Related CompoundsCHEMMEDCHEM, Issue 7 2009Hatem Abstract The role of ,-aminovinyl ketones as synthetic intermediates has been well categorised, but recent developments have shown an interesting array of applications and new chemotherapeutic potential, both in the preparation of biologically active heterocycles and as pharmacophores in their own right. Medicinal chemists are accustomed to using the products of Knoevenagel-type condensations as auxiliaries for the synthesis of N-containing heteroaromatic compounds. One such example of these chemical building blocks are ,-aminovinyl ketones,valuable synthetic intermediates that have been used in the preparation of pyridines, pyrimidines, pyrazoles, and many other heterocyclic motifs. This review highlights their recent use in the synthesis of biologically active targets as part of drug discovery programmes and in natural product synthesis. However, it is becoming increasingly evident that the enaminone motif may serve as a therapeutic pharmacophore in its own right. This review highlights the range of biological responses that ,-aminovinyl ketones elicit, including as antitumour, antibacterial, and anticonvulsant agents. Thus, with a broad spectrum of biological properties and as versatile chemical intermediates, it is clear that ,-aminovinyl ketones offer great potential in the search for new chemotherapeutic agents. [source] Synthesis of Cyclopropane-containing Building Blocks via Ir-Catalyzed Enantioselective Allylic Substitution Reaction,CHINESE JOURNAL OF CHEMISTRY, Issue 9 2010Jibao Xia Abstract Chiral cyclopropane-containing building blocks, which are very important synthetic intermediates for natural products or pharmaceuticals, were easily synthesized via Ir-catalyzed enantioselective allylic substitution reaction. [source] Enantiomeric separation of mineralocorticoid receptor (hMR) antagonists using the Chiralcel® OJ-H HPLC column with novel polar cosolvent eluent systemsCHIRALITY, Issue 6 2006V. Scott Sharp Abstract This study demonstrates the increased versatility of the Chiralcel® OJ-H stationary phase when using various alcohol/acetonitrile mobile phases. This chiral stationary phase has traditionally been employed in the normal phase mode and more recently with neat alcohols as eluents. Selected isomeric human mineralocorticoid receptor (hMR) antagonist pharmaceutical candidates and synthetic intermediates were separated using the Chiralcel® OJ-H HPLC column with novel polar cosolvent eluent systems. The capacity factors, resolution, and selectivity of the chiral separations were assessed while varying the alcohol/acetonitrile composition and alcohol identity. The mixed polar eluents provide separations that are nearly always superior to both the traditional hexane-rich and single-alcohol "polar organic" eluents for the compounds tested in this article. Chirality, 2006. © 2006 Wiley-Liss, Inc. [source] | ||||||||||||||||||||||