- Diastereoselective Synthesis of Functionalized 9-Ring Ethers (Oxonins).
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In response to the challenge of preparing medium ring ethers of the Laurencia class, a simple synthesis of functionalized, acyclic α,α'-chiral disecondary ethers has been developed.Stereocontrolled cyclization to 9-membered rings was effected in overall h
- Brandes, Arndt,Hoffmann, H. M. R.
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Read Online
- HYDROXAMATE COMPOUNDS AS ANTAGONISTS OF THE ADENOSINE A2A RECEPTOR
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The present invention relates to compounds of formula I shown below: (I) wherein R1, R2 and R3 are each as defined in the application. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of diseases or conditions in which adenosine A2a receptor activity is implicated, such as, for example, cancer.
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Paragraph 00544
(2021/01/23)
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- Enzyme-mediated enantioselective hydrolysis of 1,2-diol monotosylate derivatives bearing an unsaturated substituent
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We have succeeded in the easy preparation of optically active 1,2-diol monotosylates bearing an unsaturated substituent via enzymatic hydrolysis. Lipase PS quickly catalyzes the hydrolyses of 2-acetoxybut-3-enyl tosylate, which has a double bond, and 2-acetoxybut-3-ynyl tosylate, which has a triple bond, with excellent enantioselectivity to afford the corresponding optically active compounds. The reaction is also applicable to acetates with a longer chain, which has a double bond at the terminus. To demonstrate the applicability of this method, enantiomerically pure (R)-massoialactone, a natural coconut flavor, has been synthesized from racemic 2-acetoxypent-4-enyl tosylate in several steps. Furthermore, the enzyme can recognize the stereochemistry of olefins, and the (Z)-alkenyl structure is more suitable for the enantioselective hydrolysis than the (E)-isomer.
- Matsumoto,Oohana,Hashimoto,Usuda,Shimoda,Ohshima,Suzuki,Togawa
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p. 3981 - 3988
(2018/06/15)
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- COMPOSITIONS, SYNTHESIS, AND METHODS OF USING PHENYLCYCLOALKYLMETHYLAMINE DERIVATIVES
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The present invention provides novel phenylcycloalkylmethylamme derivatives, and methods of preparing phenylcycloalkylmethylamme derivatives. The present invention also provides methods of using phenylcycloalkylmethylamme derivatives and compositions of phenylcycloalkylmethylamme derivatives. The pharmaceutical compositions of the compounds of the present invention can be used for treating and/or preventing obesity and obesity related co- morbid indications and depression and depression related co-morbid indications.
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Page/Page column 53-54
(2013/07/19)
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- NOVEL 6-ARYLAMINO PYRIDONE CARBOXAMIDE AS MEK INHIBITORS
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The invention provides novel substituted 6-arylamino pyridone carboxamides represented by Formula I, or a pharmaceutically acceptable salt, solvate, poly- morph, ester, tautomer or prodrug thereof, and a composition comprising these compounds. The compounds provided can be used as inhibitors of MEK and are useful in the treatment of inflammatory diseases, cancer and other hyperproliferative diseases. The invention further provides a method of treatment for inflammatory diseases, cancer and other hyperproliferative diseases in mammals, especially humans.
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Page/Page column 45
(2012/05/20)
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- Copper(I)-catalyzed asymmetric desymmetrization: Synthesis of five-membered-ring compounds containing all-carbon quaternary stereocenters
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A highly stereoselective catalytic alkylation sequence for the synthesis of highly functionalized and versatile five-membered-ring compounds bearing all-carbon quaternary stereocenters was developed. Enantioselective desymmetrization of achiral cyclopentene-1,3-diones was thus executed by chiral Cu-phosphoramidite catalysts. A variety of complicated cyclopentane derivatives can be synthesized with excellent stereoselectivities using a low catalyst loading in a one-pot operation.
- Aikawa, Kohsuke,Okamoto, Tatsuya,Mikami, Koichi
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supporting information; experimental part
p. 10329 - 10332
(2012/07/30)
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- An alternate synthesis of enantiomerically pure levetiracetam (Keppra)
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A simple and efficient synthesis of levetiracetam has been achieved with high enantiopurity (>99%) starting from commercially available benzyl glycidyl ether. The method is amenable for industrial scale-up.
- Mujahid, M.,Mujumdar, P.,Sasikumar, M.,Kunte, S. S.,Muthukrishnan, M.
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p. 1512 - 1515,4
(2012/12/12)
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- An alternate synthesis of enantiomerically pure levetiracetam (Keppra)
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A simple and efficient synthesis of levetiracetam has been achieved with high enantiopurity (>99%) starting from commercially available benzyl glycidyl ether. The method is amenable for industrial scale-up.
- Mujahid,Mujumdar,Sasikumar,Kunte,Muthukrishnan
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p. 1512 - 1515
(2013/01/15)
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- THERAPEUTIC COMPOUNDS
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The invention relates to novel resolvin compounds and pharmaceutical preparations thereof. The invention further relates to methods of treatment using the novel resolvin compounds of the invention.
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Page/Page column 112
(2010/04/27)
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- N-Pyridylmethylephedrine derivatives in the catalytic asymmetric addition of diethylzinc to aldehydes and diphenylphosphinoylimines
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N-Pyridylmethyl-substituted Ephedra derivatives were synthesized by either direct alkylation or reductive alkylation of (1R,2S)-norephedrine, (1S,2S)-pseudo norephedrine, and (1R,2S)-ephedrine. These derivatives were then employed in asymmetric addition reactions with diethylzinc and aldehydes and diphenylphosphinoylimines. The use of the diastereomers from the Ephedra family allowed for a systematic evaluation of the contribution of the N-pyridylmethyl.
- Banerjee, Sucharita,Groeper, Jonathan A.,Standard, Jean M.,Hitchcock, Shawn R.
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experimental part
p. 2154 - 2161
(2010/03/03)
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- A short enantioselective synthesis of the antiepileptic agent, levetiracetam based on proline-catalyzed asymmetric α-aminooxylation
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An efficient enantioselective synthesis of a new antiepileptic drug, levetiracetam is described, in high optical purity (>99.5% ee), using proline-catalyzed α-aminooxylation of n-butyraldehyde as the key step.
- Kotkar, Shriram P.,Sudalai, Arumugam
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p. 6813 - 6815
(2007/10/03)
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- SILINANE COMPOUNDS AS CYSTEINE PROTEASE INHIBITORS
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The present invention is directed to compounds that are inhibitors of cysteine proteases, in particular, cathepsins B, K, L, F, and S and are therefore useful in treating diseases mediated by these proteases. The present invention is also directed to pharmaceutical compositions comprising these compounds and processes for preparing them. The present invention is also directed to the use of these inhibitors in combination with a therapy that causes a deleterious immune response in patients receiving the therapy.
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Page/Page column 76
(2008/06/13)
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- Synthesis of the marine compound (2R,5Z,9Z)-2-methoxyhexacosa-5,9-dienoic acid via a lipase-catalyzed resolution and a novel O-alkylation protocol
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The title compound has been synthesized by a facile route starting from 4-pentyn-1-ol. The enantioselectivity was attained by a strategy involving a lipase-catalyzed acetylation of a solid-phase immobilized long chain α-hydroxy acid. Another important feature of the synthesis was the formulation of an efficient HgO-catalyzed O-methylation of the α-hydroxy acids which proceeded without any racemization. The alkylation protocol was also highly efficient for selective mono-methylation/benzylation of symmetrical diols.
- Kulkarni, Bheemashankar A.,Sharma, Anubha,Gamre, Sunita,Chattopadhyay, Subrata
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p. 595 - 599
(2007/10/03)
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- Total synthesis of crambescidin 359.
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[structure: see text] Crambescidin 359 (4), which is the "vessel part" of the pentacyclic guanidine alkaloid ptilomycalin A (1), was synthesized for the first time based upon successive 1,3-dipolar cycloaddition reaction. This synthesis established the ab
- Nagasawa, Kazuo,Georgieva, Angelina,Koshino, Hiroyuki,Nakata, Tadashi,Kita, Tetsuya,Hashimoto, Yuichi
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p. 177 - 180
(2007/10/03)
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- Ring closing metathesis for the formation of medium ring ethers: The total synthesis of (-)-isolaurallene
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The total synthesis of the marine metabolite (-)-isolaurallene is described. Two approaches to the core nine-membered ether are presented both of which are based on a ring closing metathesis to close the cyclic ether.
- Crimmins, Michael T,Emmitte, Kyle A,Choy, Allison L
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p. 1817 - 1834
(2007/10/03)
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- Antifungal macrolides and their synthesis
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There are disclosed novel antifungal macrolides of the formula STR1 compositions containing said compounds, methods of using said compounds and a method for synthesizing the compounds.
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- Redesigning the active-site of an acyl-CoA dehydrogenase: New evidence supporting a one-base mechanism
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The acyl-CoA dehydrogenases are a family of related enzymes that share high structural homolog and a common catalytic mechanism which involves abstraction of an α-proton from the substrate by an active site glutamate residue. Several lines of investigation have shown that the position of the catalytic glutamate is conserved in most of these dehydrogenases (the E2 site), but is in a different location in two other family members (the E1 site). Using site specific in vitro mutagenesis, a double mutant rat short chain acyl-CoA dehydrogenase (rSCAD) has been constructed in which the catalytic glutamate is moved from the E2 to the E1 site (Glu368Gly/Gly247Glu). This mutant enzyme is catalytically active, but utilizes substrate less efficiently than the native enzyme (K(m) = 0.6 and 2.0 μM, and V(max) = 2.8 and 0.3 s-1 for native and mutant enzyme respectively)). In this study we show that both the wild-type and mutant rSCADs display identical stereochemical preference for catalysis-abstraction of the α-H(R) from the substrate followed by transfer of the β-H(R) to the FAD coenzyme. These results, in conjunction with molecular modeling of the native and double mutant SCAD indicate that the catalytic base in the E1 and E2 sites are topologically similar and catalytically competent. However, analysis of the 1H NMR spectra of the incubation products of these two enzymes revealed that, in contrast to the wild-type rSCAD, the Gly368Glu/Gly247Glu rSCAD could not perform γ-proton exchange of the product with the solvent, a property inherent to most acyl-CoA dehydrogenases. It is evident that the base in the mutant enzyme has access to the α-H(R) but is far removed from the γ-Hs. These findings provide further support for a one base mechanism of α- and γ-reprotonation/deprotonation catalysis by acyl-CoA dehydrogenases.
- Dakoji, Srikanth,Shin, Injae,Battaile, Kevin P.,Vockley, Jerry,Liu, Hung-Wen
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p. 2157 - 2164
(2007/10/03)
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- Synthesis of (+)-Homononactic Acid via Iodoetherification
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(+)-Homononactic acid, one of the monomers of polynactin, and its 8-epimer were synthesized. The key step was cis-selective iodoetherification of the enone or the α-silyloxyolefin intermediates constructed with Wittig-Horner or Julia coupling reactions, r
- Kiyota, Hiromasa,Abe, Masaki,Ono, Yukie,Oritani, Takayuki
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p. 1093 - 1095
(2007/10/03)
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- Total synthesis of (-)-galbonolide B and the determination of its absolute stereochemistry
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Through a trans-lactonization reaction, galbonolide B (1) was converted to 3 with the chiral secondary alcohol at C13 exposed for derivatization. Two independent methods were employed to determine the absolute chirality at C13. Both of these methods established S chirality at C13. Since the relative stereochemistry of galbonolide B had been determined from the X-ray structure, the absolute stereochemistry of galbonolide B was therefore formally established to be structure 1, which contradicted earlier speculations in the literature. A total synthesis of galbonolide B has been completed. A highly selective method was developed for the assembly of the peculiar diene unit using Martin's sulfurane reagent for the dehydration of the preceding tertiary alcohol 20. The chiral center at C4 was installed by 'contra-steric' enolate chemistry. A novel macro-Dieckmann cyclization was employed to generate the macrocycle. The desired configuration at C2 was obtained from the kinetic protonation of the corresponding enolate. Finally, a seldom used protecting group, 2,4,6-trimethylbenzylidene acetal, was employed for the glycol unit. It exhibited extremely facile hydrolysis under mildly acidic conditions without causing any decomposition of synthetic intermediates.
- Tse, Bruno
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p. 7094 - 7100
(2007/10/03)
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- 1',2'-seco-dideoxynucleosides as potential anti-HIV agents
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1',2'-seco-2',3'-Dideoxycytidine (12), -guanosine (14), -adenosine (16), and -inosine (18) were prepared from (R)-benzylglycidol as potential anti-HIV agents. When compared to ddAdo in protecting ATH8 cells, they were found to be inactive.
- Abushanab,Sarma
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- Process for preparing α-aminoalcohols
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Process for preparing an α-aminoalcohol of formula EQU1 wherein R represents hydrogen or alkyl of from 1 to 5 carbon atoms, which comprises contacting a compound of formula EQU2 wherein R has the same meaning as above, with an alcohol of formula R'-OH wherein R' represents benzyl or the group EQU3 in which R" and R"' are independently selected from hydrogen and alkyl of from 1 to 4 carbon atoms in an organic solvent, in the presence of a basic catalyst, at from about 140° to about 170°C., treating the obtained product of formula EQU4 wherein R and R' have the above meanings, with at least an equimolecular amount of a p-toluene-sulfonyl halide, at from about -5° to about 20°C. in the presence of a tertiary organic nitrogen-containing base and reacting in a closed system the resulting compound of formula EQU5 wherein R and R' are as above defined, with an excess of gaseous ammonia, in the presence of an inert organic solvent, at from about 95° to about 120°C. and recovering the resulting product as its acid addition salt.
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