- INTERMEDIATE USEFUL FOR SYNTHESIZING QUINOLYLPYRROLOPYRIMIDYL FUSED-RING COMPOUND
-
PROBLEM TO BE SOLVED: To provide a method for synthesizing or producing efficiently a quinolylpyrrolopyrimidyl fused-ring compound which has an epidermal growth factor receptor (EGFR)-inhibiting activity. SOLUTION: This invention relates to a compound expressed by formula (1), or its salt. (R1 is H, nitro, amino, hydroxy, ether, alkylthio, arylthio, etc.; R2 is halogen, a hydroxyl group, quinolyl, etc.; R3 is H or a protective group of an amino group; R4 is aldehyde or a carboxyl group when n=0, or is halogen or a hydroxyl group when n=1; R5 is an amino group or a protective group when a bond part is a single bond, or is oxo, imino, or =NRb when the bond part is a double bond; and Rb is aralkyl, acyl, alkyl sulfonyl, etc.). SELECTED DRAWING: None COPYRIGHT: (C)2018,JPOandINPIT
- -
-
Paragraph 0290; 0292-0294
(2018/03/31)
-
- Continuous-Flow Synthesis of (R)-Propylene Carbonate: An Important Intermediate in the Synthesis of Tenofovir
-
(R)-Propylene carbonate is an important intermediate in the synthesis of tenofovir pro-drugs such as tenofovir alafenamide fumarate (TAF) and tenofovir diisoproyl fumarate (TDF). Independent of the pro-drug type, tenofovir presents a chiral secondary hydroxy derivative, which can be obtained directly from (R)-propylene carbonate. Herein, we report our chemo-enzymatic continuous-flow strategy towards (R)-propylene carbonate starting from a very cheap and renewable raw material, glycerol. We were able to synthesize (R)-propylene carbonate in seven continuous-flow steps, starting from glycerol, in good-to-excellent yields (66–93 %) and excellent selectivity (E > 200).
- Suveges, Nicolas S.,Rodriguez, Anderson A.,Diederichs, Carla C.,de Souza, Stefania P.,Le?o, Raquel A. C.,Miranda, Leandro S. M.,Horta, Bruno A. C.,Pedraza, Sérgio F.,de Carvalho, Otavio V.,Pais, Karla C.,Terra, José H. C.,de Souza, Rodrigo O. M. A.
-
supporting information
p. 2931 - 2938
(2018/06/27)
-
- Engineering Homochiral Metal-Organic Frameworks by Spatially Separating 1D Chiral Metal-Peptide Ladders: Tuning the Pore Size for Enantioselective Adsorption
-
The reaction of the chiral dipeptide glycyl-L(S)-glutamate with CoII ions produces chiral ladders that can be used as rigid 1D building units. Spatial separation of these building units with linkers of different lengths allows the engineering of homochiral porous MOFs with enhanced pore sizes, pore volumes, and surface areas. This strategy enables the synthesis of a family of isoreticular MOFs, in which the pore size dictates the enantioselective adsorption of chiral molecules (in terms of their size and enantiomeric excess).
- Stylianou, Kyriakos C.,G?mez, Laura,Imaz, Inhar,Verdugo-Escamilla, Crist?bal,Ribas, Xavi,Maspoch, Daniel
-
supporting information
p. 9964 - 9969
(2015/07/07)
-
- Total Syntheses of Perenniporides
-
The total syntheses of perenniporide A (1) and related compounds have been achieved. Starting from 1,3,5-trifluorobenzene (9), difluorodienone 6 was obtained by oxidative dearomatization, which served as a platform for the high-pressure cycloaddition and for the introduction of the C3-methoxy group. The synthesis allowed access to the natural congeners 2 and 3, enabling assignment of the absolute structures of these natural products.
- Morita, Masao,Ohmori, Ken,Suzuki, Keisuke
-
supporting information
p. 5634 - 5637
(2015/12/01)
-
- Efficient Total Synthesis of Bongkrekic Acid and Apoptosis Inhibitory Activity of Its Analogues
-
Bongkrekic acid (BKA), isolated from the bacterium Burkholderia cocovenenans, is an inhibitor of adenine nucleotide translocator, which inhibits apoptosis, and is thus an important tool for the mechanistic investigation of apoptosis. An efficient total synthesis of BKA has been achieved by employing a three-component convergent strategy based on Kocienski-Julia olefination and Suzuki-Miyaura coupling. It is noteworthy that segment B has been prepared as a new doubly functionalized coupling partner, which contributes to shortening of the number of steps. Torquoselective olefination with an ynolate has also been applied for the efficient construction of an unsaturated ester. Furthermore, it is revealed that 1-methyl-2-azaadamantane N-oxyl is an excellent reagent for final oxidation to afford BKA in high yield. Based on the total synthesis, several BKA analogues were prepared for structure-activity relationship studies, which indicated that the carboxylic acid moieties were essential for the apoptosis inhibitory activity of BKA. More easily available BKA analogues with potent apoptosis inhibitory activity were also developed. Stripped BKA: The highly efficient second-generation total synthesis of bongkrekic acid (BKA), an apoptosis inhibitor, has been developed. The synthesis features a three-component convergent strategy based on a Kocienski-Julia olefination and Suzuki-Miyaura coupling. The structure-activity relationship (SAR) is also examined for the first time (see scheme).
- Matsumoto, Kenji,Suyama, Masaki,Fujita, Satoshi,Moriwaki, Takuya,Sato, Yukiko,Aso, Yoshifumi,Muroshita, Satoshi,Matsuo, Hiroshi,Monda, Keishi,Okuda, Katsuhiro,Abe, Masato,Fukunaga, Hiroyuki,Kano, Arihiro,Shindo, Mitsuru
-
supporting information
p. 11590 - 11602
(2015/08/03)
-
- AMINE SALTS OF A PROSTACYCLIN ANALOG
-
The present invention provides amine salts of the prostacyclin analogue of Formula I and processes for generating these amine salts.
- -
-
Paragraph 0321; 0322
(2015/06/03)
-
- METHODS OF SYNTHESIZING A PROSTACYCLIN ANALOG
-
The present invention provides processes for preparing a prostacyclin analogue of Formula (I) or a pharmaceutically acceptable salt thereof, wherein R10 is a linear or branched C1-6 alkyl. The processes of the present invention comprise steps that generate improved yields and fewer byproducts than traditional methods. The processes of the present invention employ reagents (e.g., the oxidizing reagent) that are less toxic that those used in the traditional methods (e.g., oxalyl chloride). Many of the processes of the present invention generate intermediates with improved e.e. and chemical purity; thereby eliminating the need of additional chromatography steps. And, the processes of the present invention are scalable to generate commercial quantities of the final compound.
- -
-
Paragraph 0340-0341
(2014/06/24)
-
- Lipophilic oligopeptides for chemo- and enantioselective acyl transfer reactions onto alcohols
-
Inspired by the extraordinary selectivities of acylases, we envisioned the use of lipophilic oligopeptidic organocatalysts for the acylative kinetic resolution/desymmetrization of rac- and meso-cycloalkane-1,2-diols. Here we describe in a full account the discovery and development process from the theoretical concept to the final catalyst, including scope and limitations. Competition experiments with various alcohols and electrophiles show the full potential of the employed oligopeptides. Additionally, we utilized NMR and IR-spectroscopic methods as well as computations to shed light on the factors responsible for the selectivity. The catalyst system can be readily modified to a multicatalyst by adding other catalytically active amino acids to the peptide backbone, enabling the stereoselective one-pot synthesis of complex molecules from simple starting materials.
- Mueller, Christian E.,Zell, Daniela,Hrdina, Radim,Wende, Raffael C.,Wanka, Lukas,Schuler, Soeren M. M.,Schreiner, Peter R.
-
p. 8465 - 8484
(2013/09/24)
-
- PROCESS FOR THE PREPARATION OF GLYCIDYL DERIVATIVES
-
There is provided a process for preparing a glycidyl derivative from 3-chloro-1,2-propanediol, comprising i) adding a phosphate salt to a solution into which 3-chloro-1,2-propanediol is dissolved into a solvent to produce glycidol, and ii) adding to the solution of step i) a base capable of releasing a glycidyl group from the glycidol and a substrate susceptible to nucleophilic attack to produce the desired glycidyl derivative by nucleophilic attack of the glycidyl group to the substrate.
- -
-
Page/Page column 6-7
(2008/06/13)
-
- A new dinuclear chiral salen complexes for asymmetric ring opening and closing reactions: Synthesis of valuable chiral intermediates
-
A new dinuclear chiral Co(salen) complexes bearing group 13 metals have been synthesized and characterized. The easily prepared complexes exhibited very high catalytic reactivity and enantioselectivity for the asymmetric ring opening of epoxides with H2O, chloride ions and carboxylic acids and consequently provide enantiomerically enriched terminal epoxides (>99% ee). It also catalyzes the asymmetric cyclization of ring opened product, to prepare optically pure terminal epoxides in one step. The homogeneous dinuclear chiral Co(salen) have been covalently immobilized on MCM-41. The potential benefits of heterogenization include facilitation of catalyst separation and recyclability requiring very simple techniques. The system described is very efficient.
- Thakur, Santosh Singh,Chen, Shu-Wei,Li, Wenji,Shin, Chang-Kyo,Kim, Seong-Jin,Koo, Yoon-Mo,Kim, Geon-Joong
-
p. 1862 - 1872
(2007/10/03)
-
- Synthesis of optically active 2-hydroxy monoesters via-kinetic resolution and asymmetric cyclization catalyzed by heterometallic chiral (salen) Co complex
-
The binuclear chiral (salen) Co complexes bearing Lewis acids of Al and Ga catalyze regio- and enantioselective ring opening of terminal epoxides with carboxylic acids. The ring opened product of epichlorohydrin with carboxylic acids followed by cyclization step in the presence of catalyst and base represent straightforward, efficient methods for the synthesis of enatiomerically enriched (>99% ee) valuable terminal epoxides. Strong synergistic effects of different Lewis acid of Co-Al and Co-Ga were exhibited in the catalytic process.
- Li, Wenji,Thakur, Santosh Singh,Chen, Shu-Wei,Shin, Chang-Kyo,Kawthekar, Rahul B.,Kim, Geon-Joong
-
p. 3453 - 3457
(2007/10/03)
-
- Highly reactive and enantioselective kinetic resolution of terminal epoxides with H2O and HCl catalyzed by new chiral (salen)Co complex linked with Al
-
The asymmetric hydrolytic kinetic resolution (HKR) of racemic terminal epoxides by new easily synthesized dimeric chiral (salen)Co bearing Al, provides a practical and straightforward method for the synthesis of enantiomerically enriched terminal epoxides (>99% ee) and diols. An inorganic acid, HCl is applied first time for the asymmetric ring opening reaction of terminal epoxides. Reactions are conveniently carried out at room temperature under an air atmosphere.
- Thakur, Santosh Singh,Li, Wenji,Kim, Seong-Jin,Kim, Geon-Joong
-
p. 2263 - 2266
(2007/10/03)
-
- Organocatalytic kinetic resolution of racemic primary alcohols using a chiral 1,2-diamine derived from (S)-proline
-
A highly efficient and good enantioselective organocatalytic asymmetric acylation of racemic primary alcohols with acyl chlorides has been achieved catalyzed by a chiral 1,2-diamine derived from (S)-proline.
- Terakado, Dai,Koutaka, Hitomi,Oriyama, Takeshi
-
p. 1157 - 1165
(2007/10/03)
-
- Synthesis of enantiomerically pure glycidol via a fully enantioselective lipase-catalyzed resolution
-
The efficient enzymatic synthesis of enantiopure 2,3-epoxypropanol (glycidol) has been achieved. The racemic glycidyl butyrate was successfully resolved by enzymatic hydrolysis using a strategy that combines different immobilization protocols and different experimental reaction conditions. A new enzyme (25 kDa lipase)-which is a lipase-like enzyme purified from the pancreatic porcine lipase (PPL) extract-immobilized on DEAE-Sepharose was selected as the optimal biocatalyst. The optimal results were obtained at pH 7, 25°C and 10% dioxane using this biocatalyst and a very high enantioselectivity for the enzyme was displayed, obtaining both (R)-(-)-glycidyl butyrate and (R)-(+)-glycidol with enantiomeric excesses >99% (E >100). The hydrolysis of (R)-(-)-glycidyl butyrate produced pure (S)-(-)-glycidol.
- Palomo, Jose M.,Segura, Rosa L.,Mateo, Cesar,Terreni, Marco,Guisan, Jose M.,Fernandez-Lafuente, Roberto
-
p. 869 - 874
(2007/10/03)
-
- Enzymatic resolution of (±)-glycidyl butyrate in aqueous media. Strong modulation of the properties of the lipase from Rhizopus oryzae via immobilization techniques
-
The enantioselectivity of the lipase from Rhizopus oryzae for the small yet highly interesting (±)-glycidyl butyrate have been greatly modulated by the use of different immobilization techniques. Thus, the enzyme immobilized by interfacial adsorption on an octyl-agarose support presented a very low enantioselectivity (E=2). This value could be improved up to an E=17 by covalently immobilizing the enzyme on the cyanogen bromide agarose. However, the best results were achieved by immobilizing the enzyme via ionic adsorption on supports coated with dextran sulfate, with an E value of 51 (ee99% at 55% conversion).
- Palomo, Jose M.,Segura, Rosa L.,Fernandez-Lorente, Gloria,Guisan, Jose M.,Fernandez-Lafuente, Roberto
-
p. 1157 - 1161
(2007/10/03)
-
- Solid oxidation catalysts, in particular for epoxidation of prochiral compounds
-
The invention concerns recyclable solid oxidation catalysts comprising a metal compound of a pentavalent or hexavalent metal M and selected among the group consisting of tantalum, vanadium, niobium, chromium, molybdenum, tungsten, grafted at the surface of a solid oxide with at least one, preferably one, covalent bond between an oxygen atom of the solid oxide and the metal M atom, the grafted metal compound having at least two alkoxy groups bound to the metal by the oxygen atom. Preferably, at least 2 alkoxy groups bound to the metal M belong to a polyol unit, preferably diol. The invention also concerns oxidation methods, in particular epoxidation methods using same.
- -
-
Page/Page column 9
(2008/06/13)
-
- Mapping the substrate selectivity of new hydrolases using colorimetric screening: Lipases from Bacillus thermocatenulatus and Ophiostoma piliferum, esterases from Pseudomonas fluorescens and Streptomyces diastatochromogenes
-
Recent advances in biochemistry and molecular biology have simplified the discovery and preparation of new hydrolases. Although these hydrolases might solve problems in organic synthesis, measuring their selectivity, especially enantioselectivity, remains tedious and time consuming. Recently, we developed a colorimetric screening method to measure the enantioselectivity of hydrolases. Here we apply this rapid screening method to map the substrate selectivity of four new hydrolases: lipases from the thermophilic Bacillus thermocatenulatus (DSM 730, BTL2) and a filamentous fungus Ophiostoma piliferum (NRRL 18917, OPL) and esterases from two bacteria, Pseudomonas fluorescens (SIK-W1, esterase I, PFE) and Streptomyces diastatochromogenes (Tue 20, SDE). We screened a general library of 29 substrates and a chiral library of 23 pairs of enantiomers. All four hydrolases catalysed the hydrolysis of unnatural substrates, but the two lipases accepted a broader range of substrates than the two esterases. As expected, the two lipases favoured more hydrophobic substrates, while the two esterases showed a preference for smaller substrates. Several moderately enantioselective reactions were identified for the solketal esters: BTL2, butyrate, E = 7.9 (R); octanoate, E = 4.9 (R) and 3-bromo-2-methyl propionate methyl esters, PFE, E = 12 (S); SDE, E = 5.6 (S). OPL showed low enantioselectivity toward all substrates tested. The current colorimetric screen could not measure the selectivity for several slow-reacting substrates. Traditional screening identified high enantioselectivity of BTL2 and PFE toward one of these slow substrates, 1-phenylethyl acetate (E>50).
- Liu, Andrew Man Fai,Somers, Neil A.,Kazlauskas, Romas J.,Brush, Terry S.,Zocher, Frank,Enzelberger, Markus M.,Bornscheuer, Uwe T.,Horsman, Geoff P.,Mezzetti, Alessandra,Schmidt-Dannert, Claudia,Schmid, Rolf D.
-
p. 545 - 556
(2007/10/03)
-
- Novel synthesis and enzymatic resolution of (±)-2,3-epoxy propyl esters
-
A novel method of synthesizing glycidyl esters (±) -2,3-epoxy propyl esters has been developed involving reaction of epichlorohydrin with sodium salt of carboxylic acids in the presence of 15-crown-5 as catalyst with excellent yields. Enzymatic resolution of these glycidyl esters by lipasePS- C has been achieved with remarkable substrate selectivity.
- Nair, Ranjeet V.,Patil, Prashant N.,Salunkhe, Manikrao M.
-
p. 2559 - 2566
(2007/10/03)
-
- Silica-supported tantalum catalysts for asymmetric epoxidations of allyl alcohols
-
Tantalum good, titanium bad: This appears to be the case for silica- supported catalysts for the asymmetric epoxidation of allyl alcohols. Complexes such as [SiO-Ta(OEt)4] were prepared from silica and [Ta(=CHCMe3)(CH2CMe3)3], and in the presence of a tartrate and an alkyl hydroperoxide, these surface tantalum compounds lead to efficient and convenient catalysts for the asymmetric epoxidation of 2-propen-1-ol (R = H) and trans-2-hexen-1-ol (R = nPr; see reaction).
- Meunier, Damien,Piechaczyk, Arnaud,De Mallmann, Aimery,Basset, Jean-Marie
-
p. 3540 - 3542
(2007/10/03)
-
- Migration of aryl groups from silicon to carbon in α,β-epoxysilanes. A new model for hypervalent silicon study
-
The reaction of (2R,3R)-3-(triphenylsilyl)glycidol (1) with n-Bu4NF·3H2O in THF, followed by treatment of the product with p-nitrobenzoyl chloride yields (2S)-glycidol p-nitrobenzoate (4) and trans-cinnamyl p-nitrobenzoate (6) in a ratio of 1:1.5. The reaction of (R)Si-(2R,3R)- or (R)Si-(2S,3S)-3-[(methyl)(phenyl)(1-naphthyl)silyl]-glycidols, 7 or 8 respectively, with n-Bu4NF·3H2O affords mixtures of the respective glycidol, trans-cinnamyl alcohol and 3-(1-naphthyl)allyl alcohol. No significant difference in the product distribution in reaction of these two diasteromers was observed.
- Achmatowicz, Barbara,Jankowski, Pawel,Wicha, Jerzy,Zarecki, Andrzej
-
p. 227 - 230
(2007/10/03)
-
- A New Aspect of Phosphorylation of Glycidol with Four-coordinate Phosphorus Dichlorides. Tandem Formation of 2-R-4-Chloromethyl-1,3,2-dioxaphospholane 2-Oxides
-
In reaction of glycidol with an equimolar amount of RP(O)Cl2 in the presence of a base, the hydroxy and epoxy groups are involved in a tandem process yielding in the first stage monoglycidyl esters of corresponding phosphorus acids and in the second stage the dioxaphospholane ring. The final stage is regio-specific and occurs without racemization of the chiral center present in the glycidyl moiety.
- Bredikhin,Lazarev,Bredikhina
-
p. 1699 - 1703
(2007/10/03)
-
- A formal synthesis of (+)-α-allokainic acid via sulfanyl radical addition-cyclization reaction
-
Sulfanyl radical addition-cyclization of the diallylamines in the presence of thiophenol and AIBN gave the 2,3,4-trisubstituted pyrrolidines which were effectively converted into the known key intermediate for the synthesis of (+)-α-allokainic acid via conversion of the phenylsulfanylmethyl group into the isopropenyl group at the 4-position.
- Miyata, Okiko,Ozawa, Yoshiki,Ninomiya, Ichiya,Aoe, Keiichi,Hiramatsu, Hajime,Naito, Takeaki
-
p. 321 - 333
(2007/10/03)
-
- A direct HPLC method for the determination of enantiomeric excess of some highly enantiomerically enriched derivatives of chiral glycidols
-
A newly developed HPLC method which requires no derivatization is used to determine accurately the enantiomeric purity of some glycidol-based derivatives that have been enantiomerically enriched by recrystallization or lipase-catalyzed kinetic resolution after the Sharpless Asymmetric Epoxidation.
- Chen, Jian
-
p. 7663 - 7666
(2007/10/02)
-
- A convenient gas chromatographic method for the optical purity determination of chiral epoxy alcohols
-
Short-chain aliphatic epoxy alcohols can be readily resolved without derivatization on a capillary gc column coated with permethylated hydroxypropyl derivative of α-cyclodextrin.
- Dougherty,Liotta,Mondimore,Shum
-
p. 4389 - 4390
(2007/10/02)
-
- Catalytic asymmetric epoxidation
-
Improved method for epoxidation of ethylenic alcohols is provided employing catalytic amounts of a titanium-glycol catalyst and a peroxide under mild conditions which provide for the continuous maintenance of an anhydrous medium during catalyst formation and during the course of the reaction. Conveniently, molecular sieves may be employed.
- -
-
-
- SUBSTRATE SPECIFICITY AND ENANTIOSELECTIVITY OF PENICILLINACYLASE CATALYZED HYDROLYSIS OF PHENACETYL ESTERS OF SYNTHETICALLY USEFUL CARBINOLS
-
Penicillinacylase from E. coli, immobilized on Eupergit C beads catalyzes the hydrolysis in water/CH3CN 10:1, at pH 7.5 and 23 deg C, of a set of O-phenylacetate esters of primary carbinols.The highest enantioselectivity is observed in the case of the 2,2-dimethyl-1,3-dioxolane-4-methanols structurally related to the penicillin (1) framework.Minor modifications of this basic structure are not altering the acceptability by the enzyme, but significantly decrease the enantioselectivity of the hydrolysis, as does the use of benzene as solvent and Sepharose-bound enzyme.
- Fuganti, Claudio,Grasselli, Piero,Servi, Stefano,Lazzarini, Ameriga,Casati, Paolo
-
p. 2575 - 2582
(2007/10/02)
-
- Catalytic Asymmetric Epoxidation and Kinetic Resolution: Modified Procedures Including in Situ Derivatization
-
The use of 3A or 4A molecular sieves ( zeoiltes ) substantially increases the scope of the titanium(IV)-catalyzed asymmetric epoxidation of primary allylic alcohols.Whereas without molecular sieves epoxidations employing only 5 to 10 mol percent Ti(O-i-Pr)4 generally led to low conversion or low enantioselectivity, in the presence of molecular sieves such reactions generally led to high conversion (>95percent) and high enantioselectivity (90-95percent ee).The epoxidations of 20 primary allylic alcohols are described.Especially noteworthy are the epoxidations of cinnamyl alcohol, 2-tetradecyl-2-propen-1-ol, allyl alcohol, and crotyl alcohol-compounds which heretofore had been considered difficult substrates for asymmetric epoxidation.In the case of allylic alcohol, the use of cumene hydroperoxide substantially increases both the reaction rate and the conversion, even in the absence of molecular sieves.In general, enantioselectivities are slightly depressed (by 1-5percent ee) relative to reactions employing 50-100 mol percent Ti(O-i-Pr)4.The epoxidation of low molecular weight allylic alcohols is especially facilitated and, in conjuction with in situ derivatization, provides for the synthesis of many epoxy alcohol synthons which were previously difficult to obtain.The kinetic resolution of four secondary allylic alcohols with 10 mol percent Ti(O-i-Pr)4 is also described.The role of molecular sieves in the reaction and the effects of variation in reaction stoichiometry, oxidant, and tartrate are discussed.
- Gao, Yun,Hanson, Robert M.,Klunder, Janice M.,Ko, Soo Y.,Masamune, Hiroko,Sharpless, K. Barry
-
p. 5765 - 5780
(2007/10/02)
-