- IMMOBILIZED PORCINE LIVER ESTERASE: A CONVENIENT REAGENT FOR THE PREPARATION OF CHIRAL BUILDING BLOCKS
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A simple method for the effective, covalent, immobilization of porcine liver esterase (PLE) is described, and the application of this reagent for the preparation of chiral building blocks on a 50-500 mmol scale is demonstrated.
- Laumen, Kurt,Reimerdes, Ernst H.,Schneider, Manfred,Goerisch, Helmut
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- Selective synthesis of ent-15-epi-F2t-isoprostane and a deuterated derivative
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Isoprostanes are an emerging class of lipid metabolites whose physiological properties are not well understood. The selective synthesis of ent-15-epi-F2t-isoprostane, an isomer active in a preliminary screening assay is described. The synthesis features a regioselective cross-metathesis on an enantiomerically enriched divinyl cyclopentyl intermediate to selectively differentiate the side-chains of the target. The route provides the isoprostane, as well as a d4-labeled analogue, in 14 steps from readily available starting materials. Georg Thieme Verlag Stuttgart.
- Shizuka, Manami,Snapper, Marc L.
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- Resolution of cis-4-O-TBS-2-cyclopenten-1,4-diol
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The resolution of cis-4-O-TBS-2-cyclopenten-1,4-diol with a few different enzymes in organic medium is described. The optical purity and yield of both the alcohol and acetate were moderate to excellent.
- Curran, Timothy T.,Hay, David A.
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- A practical and scalable process for 4-(R)-hydroxycyclopent-2-en-1-(S)- acetate by desymmetrization of meso-cyclopent-2-en-1,4-diacetate catalyzed by Trichosporon beigelii (NCIM 3326), a cheap biocatalyst
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Various yeast and fungal cultures from NCIM, NCL, Pune, India were screened for the hydrolysis of meso-cyclopent-2-en-1,4-diacetate 2 to 4-(R)- hydroxycyclopen-2-en-1-(S)-acetate 1 to provide a cheaper and more effective alternative to PLE which is currently being used for the conversion. Yeast cultures of Trichosporon species were identified as having a pro-R preference in the hydrolysis of 2; but the enantioselectivity was poor. Hence detailed medium-engineering investigations were made for the hydrolysis of 2 to 1 using a culture of Trichosporon beigelii (NCIM 3326) as catalyst. Addition of 10% v/v ethanol was found to enhance the enantioselectivity of the enzyme, affording 1 of 85% optical purity (op) in 83% yield. Further exploration of inherent consecutive kinetic resolutions to the desymmetrization afforded 1 of > 98% op in 74% chemical yield. (C) 2000 Elsevier Science Ltd.
- Kalkote, Uttam R.,Ghorpade, Sandeep R.,Joshi, Rohini R.,Ravindranathan,Bastawade, Kulbhushan B.,Gokhale, Digambar V.
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- Recombinant Pig Liver Esterase-Catalyzed Synthesis of (1S,4R)-4-Hydroxy-2-cyclopentenyl Acetate Combined with Subsequent Enantioselective Crystallization
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The recombinant pig liver esterase catalyzed hydrolysis of cis-1,4-diacetoxy-2-cyclopentene forming (1S,4R)-4-hydroxy-2-cyclopentenyl acetate was investigated and realized at preparative scale. Relevant reaction conditions were examined and optimized to achieve full conversion with an enantiomeric excess of about 86% ee. Enantiopure product was then obtained after enantioselective crystallization, which required further studies of the solid phase behavior, including its binary melting point phase diagram.
- Hinze, Janine,Süss, Philipp,Strohmaier, Silja,Bornscheuer, Uwe T.,Wardenga, Rainer,Von Langermann, Jan
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- Synthesis of tetranor-PGE1: A urinary metabolite of prostaglandins E1 and E2
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Prostaglandin E2 is produced in response to inflammation, often associated with human disease. As prostaglandins are rapidly metabolized, quantification of end urinary metabolites depend on chemical synthesis of isotopically labeled standards to support metabolite quantification. A concise synthesis of tetranor-PGE1 is described including a late stage incorporation of an isotopically labeled side-chain.
- Kimbrough, Jennifer R.,Jana, Somnath,Kim, Kwangho,Allweil, Alexander,Oates, John A.,Milne, Ginger L.,Sulikowski, Gary A.
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- Stereoselective Synthesis for Potential Isomers of Ticagrelor Key Starting Material
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Tartrate salt of carbocyclic amine 2 is one of the key starting materials for the synthesis of Ticagrelor 1. During the synthesis of 1, the isomers of 2 also need to be considered as potential impurities and characterized before establishing the specification of product. In the present work, detailed study has been carried out to synthesize the related substances of 2, and their structure characterization has been discussed.
- Mahender, Madaraboina,Yakambaram,Pandey, Jaya,Chandrashekar,Reddy, L. Amarnath,Jayashree,Bandichhor, Rakeshwar
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p. 2866 - 2872
(2019/08/30)
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- Preparation of (1R,4S)-4-hydroxycyclopent-2-en-1-yl acetate via Novozym-435 catalyzed desymmetrization of cis-3,5-Diacetoxy-1-cyclopentene
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Photooxidation of cyclopentadiene has been carried out in methanol using white light of LED lamp, rose bengal as photo initiator, and compressed air at 0 °C. Under conditions of [thiourea] ? [cyclopentadiene], the consumption of thiourea follows a pseudo-first-order reaction kinetics with half life of 75 ± 10 min; corr. coeff. r = 0.989. Slow addition of the monomer and maintaining excess thiourea concentration in reaction mass improves the yield. cis-3,5-Dihydroxy-1-cyclopentene is acetylated without isolation to obtain cis-3,5-Diacetoxy-1-cyclopentene of high purity (>99%) with overall isolated yield of 30%. Desymmetrization of the diacetate to (1R,4S)-4-hydroxycyclopent-2-en-1-yl acetate has been carried out via enzymatic transesterification with methanol in methyl tert-butyl ether (MTBE) at 5 °C using Novozym-435. The enantiomerically pure monoacetate (e.e. >99%) was obtained in 95% isolated yield. The recovered enzyme was reused for more than 10 times without loss in yield and selectivity. The entire protocol does not require purification of final product by chromatography.
- Putta, Shekhar,Reddy, Annem Mallikarjun,Sheelu, Gurrala,Reddy, B.V. Subba,Kumaraguru, Thenkrishnan
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p. 6673 - 6679
(2018/10/15)
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- Cobalt versus Osmium: Control of Both trans and cis Selectivity in Construction of the EFG Rings of Pectenotoxin 4
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Catalytic oxidative cyclisation reactions have been employed for the synthesis of the E and F rings of the complex natural product target pectenotoxin 4. The choice of metal catalyst (cobalt- or osmium-based) allowed for the formation of THF rings with either trans or cis stereoselectivity. Fragment union using a modified Julia reaction then enabled the synthesis of an advanced synthetic intermediate containing the EF and G rings of the target.
- Roushanbakhti, Ahria,Liu, Yifan,Winship, Paul C. M.,Tucker, Michael J.,Akhtar, Wasim M.,Walter, Daryl S.,Wrigley, Gail,Donohoe, Timothy J.
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supporting information
p. 14883 - 14887
(2017/10/24)
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- Novel Imidazo[4,5-c]Quinoline And Imidazo[4,5-c][1,5]Naphthyridine Derivatives As LRRK2 Inhibitors
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The present invention provides novel imidazo[4,5-c]quinoline and imidazo[4,5-c][1,5]naphthyridine derivatives of Formula (I), and the pharmaceutically acceptable salts thereof wherein R1, R1a, R1b, R2, R4, R5, R6, X and Z are as defined in the specification. The invention is also directed to pharmaceutical compositions comprising the compounds of Formula (I) and to use of the compounds in the treatment of diseases associated with LRRK2, such as neurodegenerative diseases including Parkinson's disease or Alzheimer's disease, cancer, Crohn's disease or leprosy.
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Paragraph 0171
(2017/04/04)
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- Chemoenzymatic routes to cyclopentenols: The role of protecting groups on stereo- and enantioselectivity
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Enantiopure (R)-4-triisopropylsilyloxycyclopent-2-en-1-one was obtained through short sequences including either the enzymatic resolution of racemic cis-4-triisopropylsilyloxycyclopent-2-en-1-ol or the enzymatic desymmetrization of cis-cyclopent-2-en-1,3-diol. Alternatively, the enantiopure (S)-4-triisopropylsilyloxycyclopent-2-en-1-one was very efficiently obtained from diacetate of cis-cyclopent-2-en-1,3-diol using enzymatic desymmetrization with CAL-B. In these sequences, TIPS proved to be the best protecting group.
- Specklin, Simon,Dikova, Anna,Blanc, Aurélien,Weibel, Jean-Marc,Pale, Patrick
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p. 6987 - 6991
(2015/02/02)
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- Enzyme immobilised novel core-shell superparamagnetic nanocomposites for enantioselective formation of 4-(R)-hydroxycyclopent-2-en-1-(S)-acetate
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Lipase immobilized novel high surface area core-shell superparamagnetic nanoparticles have been fabricated and used as efficient reusable catalysts for the selective production of pharmaceutically important chiral isomers from meso-cyclopent-2-en-1,4-diac
- Sharifabad, Maneea Eizadi,Hodgson, Ben,Jellite, Mourad,Mercer, Tim,Sen, Tapas
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supporting information
p. 11185 - 11187
(2014/11/08)
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- PHOSPHONUCLEOSIDES USEFUL IN THE TREATMENT OF VIRAL DISORDERS
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A first aspect of the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt or prodrug thereof, wherein the groups are as defined in the claims. Further aspects of the invention relate to pharmaceutical compositions comprising compounds of formula (I), and the use of compounds of formula (I) in the preparation of a medicament for treating a viral disorder.
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Page/Page column 43; 44
(2014/06/11)
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- PREPARATION OF LUBIPROSTONE
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Aspects of the present application relate to process for the preparation of lubiprostone.
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Paragraph 0109
(2013/07/25)
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- Palladium-catalyzed 1,4-addition of carboxylic acids to butadiene monoxide
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Palladium complexes catalyze the 1,4-addition of acetic acid to butadiene monoxide to give 4-hydroxybut-2-en-1-yl acetate. The highest 1,4-/1,2-addition selectivity of 18.9 was achieved. The reaction seems to proceed via a Wacker-like mechanism. Copyright
- Hamasaki, Akiyuki,Maruta, Shuhei,Nakamura, Aki,Tokunaga, Makoto
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supporting information
p. 2129 - 2134
(2012/11/07)
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- Studies toward the total synthesis of carba analogue of motif C of M. TB cell wall AG complex
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Herein we describe the synthesis of the carba analogue of motif C of arabinogalactan complex present in M. tuberculosis cell wall. Pd(0) catalyzed allylic alkylation and Fraser-Reid's glycosidation are the two key reactions that were employed for the synthesis of central glycosyl accepter unit and the glycosylation respectively.
- Gurjar, Mukund K.,Reddy, Challa Nageswar,Kalkote, Uttam R.,Chorghade, Mukund S.
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scheme or table
p. 909 - 925
(2010/10/20)
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- Method for the Production of a Compound, Comprising a Free Hydroxyl Group and a Hydroxyl Group Which is Protected by an Ester Function by Enzymatic Reaction
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The invention relates to a method for the production of a compound comprising a free hydroxyl group and a hydroxyl group which is protected by an ester function by enzymatic reaction, using a lipase EC 3.1.1.3. The invention also relates to the use of the resultant compound as an intermediate for the production of medicaments and pharmaceutical products.
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Page/Page column 4-5
(2008/06/13)
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- Asymmetric synthesis of cis-3,5-diacetoxycyclopent-1-ene using metagenome-derived hydrolases
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Esterases and lipases originating from the metagenome (environmental DNA) were studied for the asymmetric hydrolysis of cis-3,5-diacetoxycyclopent-1-ene 1. Out of 83 enzymes, 35 were found to be active. Subsequent analytical and laboratory scale reactions identified three enzymes showing excellent (-)-preference and one enzyme with excellent (+)-selectivity exceeding even the performance of recombinant or commercial pig liver esterase, which is known as the best biocatalyst for this compound.
- Bruesehaber, Elke,Boettcher, Dominique,Liebeton, Klaus,Eck, Juergen,Naumer, Christian,Bornscheuer, Uwe T.
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p. 730 - 732
(2008/09/20)
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- Synthesis of enantiomerically pure cyclopentene building blocks
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An efficient synthesis of the enantiomerically pure cis-annulated cyclopentenes 2 and ent-2 was established by the use of an enzymatic transesterification and hydrolysis, respectively, followed by an S N2-type substitution with a benzyloxymethyl cuprate and a sigmatropic rearrangement. The advantage of this approach is the short sequence combined with an excellent overall yield and an enantiomeric excess of 99%. Georg Thieme Verlag Stuttgart.
- Tietze, Lutz F.,Stadler, Christian,B?hnke, Niels,Brasche, Gordon,Grube, Alexander
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p. 485 - 487
(2007/12/27)
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- Synthesis of novel spinosyn a analogues by Pd-mediated transformations
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The concept of modern crop protection demands for a continuous supply of new or modified established pesticides to avoid the development of serious resistances. Recent reports on the insecticidal spinosyns 1 and 2 show that also this class of pest managing agents is increasingly exposed to the formation of resistances. The synthesis of new derivatives is therefore highly desirable. We describe in this paper a convergent approach towards novel enantiopure spinosyn A analogues of type 3, which is based on investigations of structure-activity relationships and employs a twofold Heck reaction as key step for the preparation of the tricyclic backbone assembly.
- Tietze, Lutz F.,Brasche, Gordon,Grube, Alexander,Boehnke, Niels,Stadler, Christian
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p. 8543 - 8563
(2008/04/01)
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- Process for preparing enantiomerically enriched (1S,4R) 1-acetoxy-4-hydroxycyclopent-2-ene
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This invention relates to a process for the synthesis of enantiomerically enriched (1S,4R) 1-acetoxy-4-hydroxycyclopent-2-ene of Formula I, a compound useful as an intermediate in the synthesis of prostaglandins and prostanoids.
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Page/Page column 5
(2008/06/13)
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- Biotransformations in low-boiling hydrofluorocarbon solvents
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Solvent solutions: Low-boiling hydrofluorocarbons (see examples) are excellent solvents for lipase-catalyzed reactions and ideal replacements for conventional organic solvents and supercritical fluids as media for nonaqueous biotransformations. Notably increased rates, yields, and enantioselectivities were observed with the model kinetic resolution of (±)-1-phenylethanol and the desymmetrization of weso-2-cyclopentene-1 ,4-diol.
- Saul, Simon,Corr, Stuart,Micklefield, Jason
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p. 5519 - 5523
(2007/10/03)
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- Desymmetrization of meso-cyclopenten-cis-1,4-diol to 4-(R)- hydroxycyclopent-2-en-1-(S)-acetate by irreversible transesterification using Chirazyme
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The parameter optimization study for the desymmetrization of meso- cyclopenten-1,4-diol 1 through irreversible transesterification using an immobilized lipase from Mucor meihei, i.e., Lipozyme/Chirazyme is presented. The enzyme was studied for the transesterification of 1 in various organic solvents by varying reaction parameters such as the nature of acyl donor, temperature, enzyme quantity etc., to afford optically active 4-(R)- hydroxycyclopent-2-en-1-(S)-acetate 2 of >98% enantiomeric excess in >60% yield.
- Ghorpade, Sandeep R.,Kharul, Rajendra K.,Joshi, Rohini R.,Kalkote, Uttam R.,Ravindranathan
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p. 891 - 899
(2007/10/03)
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- Development of the carbocyclic nucleoside MDL 201449A: A tumor necrosis factor-α inhibitor
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An efficient synthesis of (1S,4R)-(-)-4-tert-butyldimethylsilyloxy-2-cyclopentenyl acetate and (1R,4S)-(-)-4-tert-butyldimethylsilyloxy-2-cyclopentenol is described utilizing a furfuryl alcohol rearrangement, followed by a lithium aluminum hydride reduction with high facial selectivity and an efficient enzymatic resolution with pancreatin. Both of these intermediates were successfully utilized in the preparation of the carbocyclic nucleoside 9N-[(1′R,3′R)-trans-3′-hydroxycyclopentanyl]adenine hydrochloride, an agent which inhibits the formation of tumor necrosis factor-α.
- Watson, Timothy J.N.,Curran, Timothy T.,Hay, David A.,Shah, Ramnik S.,Wenstrup, David L.,Webster, Mark E.
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p. 357 - 365
(2013/09/08)
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- The preparation of optically active 2-cyclopenten-1,4-diol derivatives from furfuryl alcohol
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The preparation and enzymatic resolution of several cis-mono-4-O-protected-2-cyclopenten-1,4-diols are described. The process starts with inexpensive furfuryl alcohol and lends itself to the preparation of multigram quantities of various protected, optically active 2-cyclopenten-1,4-diol derivatives. Stereoselective reduction of 4-O-protected-2-cyclopentenone to the cis-mono-O-protected-2-cyclopenten-1,4-diol using LiAlH4/LiI or Red-Al/NaI is described. Subsequent pancreatin-promoted, stereoselective acylation was conducted on these cis-(+/-)-mono-O-protected-cyclopenten-1,4-diols to afford the corresponding alcohols and acetates in moderate to excellent enantioselectivities.
- Curran, Timothy T.,Hay, David A.,Koegel, Christopher P.,Evans, Jonathan C.
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p. 1983 - 2004
(2007/10/03)
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- Enzymatic Asymmetrization of meso-2-Cycloalken-1,4-diols and Their Diacetates in Organic and Aqueous Media
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meso-2-Cycloalken-1,4-diols or the corresponding diacetates with five-, six-, and seven-membered rings were subjected to enzymatic asymmetrizations utilizing a recombinant version of lipase B from Candida antarctica (Novo SP-435) in organic or aqueous media.
- Johnson, Carl R.,Bis, Scott J.
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p. 7287 - 7290
(2007/10/02)
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- Enzymes in Organic Synthesis. 4. Investigation of the Pancreatin-Catalyzed Acylation of cis-Cyclopent-2-ene-1,4-diol with Various Trichloroethyl and Vinyl Alkanoates
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During the pancreatin-catalyzed acetylation of the meso-diol 1 with 2,2,2-trichloroethyl acetate (2a) in tetrahydrofuran/triethylamine, the enantiomeric monoacetates 3a and ent-3a are formed at nearly equal rates. ent-3a is rapidly acetylated in a second enzyme-catalyzed step, forming 4a, whereas 3a resists further enzymatic acetylation.Thus, the monoacetate 3a can be obtained in 48 percent yield with an enantiomeric excess (e.e.) of more than 99 percent. 2,2,2-Trichloroethyl propanoate and butanoate give the corresponding monoacylation products even in slightly better yields, whereas the octanoate affords the monoacylation product with a lower enantiomeric excess. 2,2,2-Trichloroethyl monochloroacetate provides the monoacylation product in a 40 percent yield with an e.e. of 90 percent.The dichloroacetate, however, affords the diacylation product exclusively in an enzyme-independent chemical reaction.With the 2,2,2-trichloroethyl esters of isobutyric, phenylacetic, and benzoic acid no transesterification could be achieved within 24 hours.The application of vinyl acetate, however, represents a significant improvement in the synthesis of enantiomerically pure monoacetate 3a from meso-diol 1.
- Theil, Fritz,Schick, Hans,Lapitskaya, Margarita A.,Pivnitsky, Kasimir K.
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p. 195 - 200
(2007/10/02)
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- LIPASE-CATALYZED IRREVERSIBLE TRANSESTERIFICATION USING ENOL ESTERS: XAD-8 IMMOBILIZED LIPOPROTEIN LIPASE-CATALYZED RESOLUTION OF SECONDARY ALCOHOLS
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Procedures for preparation of XAD-8 immobilized lipoprotein lipase and the resolution of secondary alcohols of synthetic value in organic solvents using this immobilized enzyme have been developed.
- Hsu, Shu-Hui,Wu, Shihn-Sheng,Wang, Yi-Fong,Wong, Chi-Huey
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p. 6403 - 6406
(2007/10/02)
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- A Novel Asymmetric Synthesis of Chiral Cyclopentanoid Building Blocks by the Use of Chiral Lithium Amide
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Enantioselective deprotonation of meso-epoxides, derived from 3-cyclopenten-1-ol, was examined using chiral lithium amide.Chiral cis-4-t-butyldimethylsiloxy-2-cyclopenten-1-ol, cis-4-tetrahydropyranyloxy-2-cyclopenten-1-ol, and their trans-isomers, which are useful chiral building blocks for the synthesis of cyclopentanoid natural compounds, were obtained with high enantiomeric excesses (72 - 90 percent ee).Both (R)- and (S)-4-hydroxy-2-cyclopenten-1-one were derived from (1S,4R)-4-t-butyldimethylsiloxy)-2-cyclopenten-1-ol stereospecifically.
- Asami, Masatoshi
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p. 1402 - 1408
(2007/10/02)
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- ENANTIOSELECTIVE SYNTHESIS OF 3(S)-ACETOXY-5(R)-HYDROXYCYCLOPENT-1-ENE BY AN ENZYMATIC TRANSESTERIFICATION IN ORGANIC SOLVENTS
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3(S)-acetoxy-5(R)-hydroxycyclopent-1-ene has been obtained in 50percent yield with an enantiomeric excess >/= 99percent by porcine pancreatic lipase-catalysed transacetylation of cis-3,5-dihydroxycyclopent-1-ene in anhydrous pyridine.
- Jommi, Giancarlo,Orsini, Fulvia,Sisti, Massimo,Verotta, Luisella
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p. 863 - 864
(2007/10/02)
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- Synthesis of (1S,4R)-(-)-40Hydroxy-2-cyclopentenyl Acetate by a Highly Enantioselective Enzyme-Catalyzed Transesterification in Organic Solvents
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(1S,4R)-(-)-4-Hydroxy-2-cyclopentenyl acetate (2), a versatile intermediate in prostaglandin syntheses, was readily prepared by an efficient enzyme-catalyzed enantioselective monoacetylation of cis-2-cyclopenten-1,4-diol (1) with 2,2,2-trichloroethyl acetate in the organic solvent system triethylamine/tetrahydrofuran.The chemical yield reached nearly 50percent.The enantiomeric excess of the crude product was 95percent.It could be raised to more than 99percent by a single recrystalization.Commercially available pancreatin, a crude enzyme preparation from porcine pancreas, was used as biocatalyst.
- Theil, Fritz,Ballschuh, Sibylle,Schick, Hans,Haupt, Monika,Haefner, Barbara,Schwarz, Sigfrid
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p. 540 - 541
(2007/10/02)
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- Process for the preparation of (1S, 4R)-4-hydroxy-2-cyclopentenyl esters
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Optically pure (1S, 4R)-4-hydroxy-2-cyclopentyl ester of the formula STR1 in which Ac is an aliphatic acyl radical having 1 to 18 carbon atoms, is produced by contacting a meso such as porcine liver esterase. The products are useful in synthesizing cyclopentanoid products such as brefeldin A, sesquiterpenes and prostaglandins.
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- ENZYMATIC HYDROLYSIS OF PROCHIRAL CIS-1,4-DIACYL-2-CYCLOPENTADIENOLS: PREPARATION OF (1S,4R)- AND (1R,4S)-4-HYDROXY-2-CYCLOPENTENYLDERIVATIVES, VERSATILE BUILDING BLOCKS FOR CYCLOPENTANOID NATURAL PRODUCTS.
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The enzymatic hydrolysis of prochiral diesters 1 was studied in presence of seven enzymatic systems, resulting in the enantioselective preparation of both enantiomeric series of chiral building blocks 2-4 and ent-2-4 on a preparative scale.
- Laumen, Kurt,Schneider, Manfred
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p. 5875 - 5878
(2007/10/02)
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