- A method for high-throughput screening of enantioselective catalysts
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About 1000 catalytic or stoichiometric asymmetric reactions of racemic compounds or prochiral substrates bearing enantiotopic groups can be analyzed per day. In this highly efficient method the enantioselectivity is determined by electrospray ionization mass spectrometry using isotopically labeled substrates. The picture shows the mass spectrum of the mixture obtained upon hydrolysis of 1 to afford the pseudo-enantiomeric products 2 and 3.
- Reetz, Manfred T.,Becker, Michael H.,Klein, Heinz-Werner,Stoeckigt, Detlef
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Read Online
- Studies towards the total synthesis of an epoxy isoprostane phospholipid, a potent activator of endothelial cells.
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We report studies toward the total synthesis of an epoxy isoprostane, namely the preparation of compound 9 which is an analogue of the elimination product 7 of the naturally occurring epoxy isoprostane 4 by a straightforward route using a three-component coupling, and have shown by several spectroscopic criteria that it closely resembles the natural material.
- Jung, Michael E,Kers, Annika,Subbanagounder, Ganesamoorthy,Berliner, Judith A
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- PALLADIUM-CATALYZED INTRAMOLECULAR OLEFIN ALLYLATIONS: STEREOCONTROLLED SYNTHESES OF BICYCLIC SYSTEMS AND EVIDENCE FOR AN ALLYLPALLADIUM/OLEFIN-CIS-INSERTION
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Pd(0)-catalyzed cyclizations of (1-acetoxy-3-alkenyl)-2-cycloalkenes 3, 6 and 12 provide bicyclic systems in high diastereo- (5, 8) and enantio-meric (14) purity consistent with a predominant allylpalladium/alkene cis- insertion.
- Oppolzer, Wolfgang,Gaudin, Jean-Marc,Birkinshaw, Timothy N.
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- A HIGHLY ENANTIOSELECTIVE HYDROLYSIS OF CIS-3,5-DIACETOXYCYCLOPENT-1-ENE. AN ENZYMATIC PREPARATION OF 3(R)-ACETOXY-5(S)-HYDROXYCYCLOPENT-1-ENE.
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Exposure of cis-3,5-diacetoxycyclopent-1-ene (3) to the hydrolase enzyme acetylcholinesterase (from electric eel) affords in 94percent yield 3(R)-acetoxy-5(S)-hydroxycyclopent-1-ene (2) with an e.e. of 96percent (greater than 99percent e.e. after one recrystallization).
- Deardorff, Donald R.,Matthews, A. J.,McMeekin, D. Scott,Craney, Chris L.
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Read Online
- Acylative desymmetrization of cyclic meso-1,3-diols by chiral DMAP derivatives
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An efficient enantioselective acylative desymmetrization of cyclic meso-1,3-diols was developed by using a chiral DMAP derivative 1e having a 1,1¤-binaphthyl unit. The reactions required only 0.5mol% of the catalyst and showed good to excellent enantioselectivity. With this transformation, 5a, a key building block for the synthesis of natural products, was easily obtained in almost enantiomerically pure form after a single recrystallization. Control experiments revealed that tert-alcohol units on the catalyst were responsible for both the catalytic activity and enantioselectivity.
- Mandai, Hiroki,Hironaka, Tsubasa,Mitsudo, Koichi,Suga, Seiji
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supporting information
p. 471 - 474
(2021/03/15)
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- Total Synthesis of the Alleged Structure of Crenarchaeol Enables Structure Revision**
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Crenarchaeol is a glycerol dialkyl glycerol tetraether lipid produced exclusively in Archaea of the phylum Thaumarchaeota. This membrane-spanning lipid is undoubtedly the structurally most sophisticated of all known archaeal lipids and an iconic molecule in organic geochemistry. The 66-membered macrocycle possesses a unique chemical structure featuring 22 mostly remote stereocenters, and a cyclohexane ring connected by a single bond to a cyclopentane ring. Herein we report the first total synthesis of the proposed structure of crenarchaeol. Comparison with natural crenarchaeol allowed us to propose a revised structure of crenarchaeol, wherein one of the 22 stereocenters is inverted.
- Cunha, Ana V.,Havenith, Remco W. A.,Holzheimer, Mira,Minnaard, Adriaan J.,Schouten, Stefan,Sinninghe Damsté, Jaap S.
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supporting information
p. 17504 - 17513
(2021/07/06)
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- Enantioselective Total Synthesis of (+)-Nordasycarpidone, (+)-Dasycarpidone, and (+)-Uleine
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The structure of uleine type alkaloids is characterized by the presence of a bridged tetracyclic hexahydro-1H-1,5-methanoazocino[4,3-b]indole ring system 1. Various strategies have been developed to access this polycyclic structural motif. We report herein a one-step conversion of appropriately functionalized 1,3,4-trisubstituted cyclopent-1-ene to 1 by way of an integrated oxidation/reduction/cyclization (iORC) process. This domino sequence, initiated by oxidative cleavage of cyclopentene ring, generated subsequently a cyclohexenone, an indole and a 1,3-bridged piperidine ring through formation of one C?C and two C?N bonds. Compound 1 is subsequently converted to nordasycarpidone, dasycarpidone and uleine. The chirality of the molecule was introduced by enzymatic desymmetrization of commercially available meso cis-3,5-diacetoxy-1-cyclopentene.
- Delayre, Bastien,Fung, Cédric,Wang, Qian,Zhu, Jieping
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- Photo-oxidation of Cyclopentadiene Using Continuous Processing: Application to the Synthesis of (1 R,4 S)-4-Hydroxycyclopent-2-en-1-yl Acetate
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(1R,4S)-4-Hydroxycyclopent-2-en-1-yl acetate is a chiral small building block that was requested to advance several Pfizer programs into the clinic. Pfizer and Syncom partnered to develop a photo-oxidation process of cyclopentadiene using a flow approach followed by subsequent bis-acetylation of the meso diol and final biocatalytic desymmetrization. This continuous process was demonstrated on a 6 g·h-1 input and is amenable to larger scale. The optimization and scale-up of this sequence is described therein.
- Allais, Christophe,Herrero-Gomez, Elena,Huck, Lena,Keene, Nandell F.,Li, Bryan,Pouwer, Kees,Rioz-Martínez, Ana,Van Der Loo, Cornelis H. M.
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p. 2304 - 2310
(2020/11/23)
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- TiCl3-Mediated Synthesis of 2,3,3-Trisubstituted Indolenines: Total Synthesis of (+)-1,2-Dehydroaspidospermidine, (+)-Condyfoline, and (?)-Tubifoline
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2,3,3-Trisubstituted indolenine constitutes an integral part of many biologically important monoterpene indole alkaloids. We report herein an unprecedented access to this skeleton by a TiCl3-mediated reductive cyclization of tetrasubstituted alkenes bearing a 2-nitrophenyl substituent. The proof of concept is demonstrated firstly by accomplishing a concise total synthesis of (+)-1,2-dehydroaspidospermidine featuring a late-stage application of this key transformation. A sequence of reduction of nitroarene to nitrosoarene followed by 6π-electron-5-atom electrocyclization and a 1,2-alkyl shift of the resulting nitrone intermediate was proposed to account for the reaction outcome. A subsequent total synthesis of (+)-condyfoline not only illustrates the generality of the reaction, but also provides a mechanistic insight into the nature of the 1,2-alkyl shift. The exclusive formation of (+)-condyfoline indicates that the 1,2-alkyl migration follows a concerted Wagner–Meerwein pathway, rather than a stepwise retro-Mannich/Mannich reaction sequence. Conditions for almost quantitative conversion of (+)-condyfoline to (?)-tubifoline by way of a retro-Mannich/1,3-prototropy/transannular cyclization cascade are also documented.
- Delayre, Bastien,Piemontesi, Cyril,Wang, Qian,Zhu, Jieping
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supporting information
p. 13990 - 13997
(2020/06/10)
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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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- Wolff/Cope Approach to the AB Ring of the Sesterterpenoid Variecolin
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A stereoselective synthesis of the AB ring of the complex sesterterpenoid variecolin is presented. Our strategy features the development of a tandem Wolff/Cope rearrangement of α-diazo cyclobutyl ketones for the construction of fused, 8-membered carbocycles. Preliminary studies revealed a facile Wolff rearrangement but a difficult vinyl ketene cyclobutane Cope rearrangement. We have leveraged an efficient microwave-promoted tandem rearrangement to prepare the desired functionalized cyclooctadienones that we envision as potential key intermediates in the convergent synthesis of variecolin.
- Krout, Michael R.,Henry, Christopher E.,Jensen, Thomas,Wu, Kun-Liang,Virgil, Scott C.,Stoltz, Brian M.
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p. 6995 - 7009
(2018/07/15)
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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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p. 1258 - 1264
(2016/07/23)
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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
(2014/06/11)
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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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p. 2129 - 2134
(2012/11/07)
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- IMPROVED PROCESSES FOR PREPARING PURE (3AR,4S,6R,6AS)-6-AMINO-2,2-DIMETHYLTETRAHDRO-3AH-CYCLOPENTA[D] [1,3]-DIOXOL-4-OL AND ITS KEY STARTING MATERIAL
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Provided herein is an improved, commercially viable and industrially advantageous process for the preparation of a ticagrelor intermediate, (3aR,4S,6R,6aS)-6-amino-2,2- dimethyltetrahydro-3aH-cyclopenta[d][l,3]-dioxol-4-ol, which is useful for preparing ticagrelor or a pharmaceutically acceptable salt thereof in high yield and purity. The present invention further relates to an improved process for the preparation of (lS,4R)-cis-4-acetoxy- 2-cyclopenten-l-ol, which is a key starting material in the preparation of the ticagrelor intermediate.
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- FUSED TRICYCLIC ETHER CARBAMATES AND THEIR USE
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Tricylic ether carbamates that inhibit HIV proteolytic enzymes and processes for preparing the compounds are describes. Methods of using the disclosed compounds for treating patients infected with HIV are also described.
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Page/Page column 27; 28
(2012/03/26)
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- Divergent synthesis and chemical reactivity of bicyclic lactone fragments of complex rearranged spongian diterpenes
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The synthesis and direct comparison of the chemical reactivity of the two highly oxidized bicyclic lactone fragments found in rearranged spongian diterpenes (8-substituted 6-acetoxy-2,7-dioxabicyclo[3.2.1]octan-3-one and 6-substituted 7-acetoxy-2,8-dioxabicyclo[3.3.0]octan-3-one) are reported. Details of the first synthesis of the 6-acetoxy-2,7-dioxabicyclo[3.2.1]octan-3- one ring system, including an examination of several possibilities for the key bridging cyclization reaction, are described. In addition, the first synthesis of 7-acetoxy-2,8-dioxabicyclo[3.3.0]octanones containing quaternary carbon substituents at C6 is disclosed. Aspects of the chemical reactivity and Golgi-modifying properties of these bicyclic lactone analogs of rearranged spongian diterpenes are also reported. Under both acidic and basic conditions, 8-substituted 2,7-dioxabicyclo[3.2.1]octanones are converted to 6-substituted-2,8-dioxabicyclo[3.3.0]octanones. Moreover, these dioxabicyclic lactones react with primary amines and lysine side chains of lysozyme to form substituted pyrroles, a conjugation that could be responsible for the unique biological properties of these compounds. These studies demonstrate that acetoxylation adjacent to the lactone carbonyl group, in either the bridged or fused series, is required to produce fragmented Golgi membranes in the pericentriolar region that is characteristic of macfarlandin E.
- Schnermann, Martin J.,Beaudry, Christopher M.,Genung, Nathan E.,Canham, Stephen M.,Untiedt, Nicholas L.,Karanikolas, Breanne D. W.,Suetterlin, Christine,Overman, Larry E.
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supporting information; experimental part
p. 17494 - 17503
(2011/12/04)
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- Stereoselective synthesis of epi-jasmonic acid, tuberonic acid, and 12-oxo-PDA
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epi-Jasmonic acid (epi-JA) and tuberonic acid (TA) were synthesized from the key aldehyde, all cis-2-(2-hydroxy-5-vinylcyclopentyl)acetaldehyde (14), which was in turn prepared stereoselectively from the (1R)-acetate of 4-cyclopentene-1,3-diol (10) through SN2-type allylic substitution with CH2CHMgBr followed by Mitsunobu inversion, Eschenmoser-Claisen rearrangement, and regioselective Swern oxidation of the corresponding bis-TES ether (13). Wittig reaction of the aldehyde 14 with [Ph3P(CH 2)Me]+Br- followed by oxidation afforded epi-JA (3) stereoselectivity over the trans isomer. Similarly, TA (5) was synthesized. Furthermore, the above findings were applied successfully to improve the total efficiency of the previous synthesis of 12-oxo-PDA (1).
- Nonaka, Hisato,Ogawa, Narihito,Maeda, Noriaki,Wang, Yong-Gang,Kobayashi, Yuichi
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body text
p. 5212 - 5223
(2010/12/25)
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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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(2008/06/13)
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- CYCLOPENTENE DIOL MONOACETATE DERIVATIVES
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A process for the preparation of organic compounds of formula (I), wherein R1is as described herein.
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Page/Page column 9; 12; 14-15
(2008/12/05)
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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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- Pd(0) catalyzed intramolecular alkylation: stereoselective synthesis of furan and isoxazoline-2-oxide analogs
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New optically pure isoxazoline-2-oxide and furan analogs have been synthesized using Pd(0) catalyzed intramolecular cyclizations. Starting from a meso-diol, optically pure compounds were prepared without utilizing chiral ligands at any stage of the synthesis. The stereochemical outcome of the product (>99% ee) was influenced by desymmetrization catalyzed by Pseudomonas cepacia lipase and the stereoselective nature of the palladium catalyzed transformations.
- Khan, Pasha M.,Wu, Ruizhi,Bisht, Kirpal S.
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p. 1116 - 1126
(2007/10/03)
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- Total synthesis of the epoxy isoprostane phospholipids PEIPC and PECPC
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(Chemical Equation Presented) A total synthesis of the naturally occurring hydroxy ketone PEIPC 1, a compound that plays a role in endothelial activation in atherosclerosis, has been completed via a triply convergent preparation of a protected EI derivative 13 from 3,5-diacetoxycyclopentene 7, pentane-1,5-diol, and vinyllithium, using Sharpless epoxidation and enzymatic resolution as key steps. Final coupling with lyso-PC 16 and silyl group deprotection gave PECPC 2 and PEIPC 1, which showed the same activity as natural PECPC and PEIPC.
- Jung, Michael E.,Berliner, Judith A.,Angst, Daniela,Yue, Dawei,Koroniak, Lukasz,Watson, Andrew D.,Li, Rongsong
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p. 3933 - 3935
(2007/10/03)
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- Toward the total syntheses of pepluanin A and euphosalicin: Concise route to a highly oxygenated cyclopentane as a common intermediate
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A substrate controlled asymmetric synthesis is described of a highly functionalized cyclopentanyl vinyl triflate which serves as an advanced intermediate in the total synthesis of the novel multidrug resistance reversing jatrophanes pepluanin A and euphosalicin. Key steps are a Claisen-Eschenmoser rearrangement followed by hydroxy-lactonization, intramolecular trans-lactonization, Davis hydroxylation and regioselective enoltriflate formation.
- Gilbert, Michael W.,Galkina, Anna,Mulzer, Johann
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p. 2558 - 2562
(2007/10/03)
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- A novel approach to bis-isoxazolines using a latent form of cyclopentadienone
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The synthesis of a range of both racemic and homochiral 4-alkyl- and 4-aryl-8-hydroxy-2-oxa-3-azabicyclo[3.3.0]oct-3-en-6-ones (isoxazolines) from the 1,3-dipolar cycloaddition reactions between alky- and aryl-nitrile oxides and 4-alkoxycyclopent-2-enomes was described. Elimination of the 8-hydroxy group and subsequent additional cycloaddition reactions provided 5,9-disubstituted-3,11-dioxa-4,10-diazatricyclo[6.3.01,8.02 ,6]undeca-4,9-dien-7-ones formally derived fromcyclopentadienone. The results showed that in the structures studied the nonhydrogen atoms were included in geometric positions and given thermal parameters equivalent to 1.2 times those of the atoms to which they were attached.
- Basra, Sanjivanjit K.,Drew, Michael G.B.,Mann, John,Kane, Peter D.
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p. 3592 - 3598
(2007/10/03)
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- Nucleosides and nucleotides. 186. Synthesis and biological activities of pyrimidine carbocyclic nucleosides with a hydroxyamino group instead of a hydroxymethyl group at the 4'-position of the sugar moiety
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Pyrimidine carbocyclic nucleosides with a hydroxyamino group instead of a hydroxymethyl group at the 4'-position of the sugar moiety were designed as potential antitumor and/or antiviral agents. Pd (O)-catalyzed reactions of enantiomerically pure (+)-(1R,4S)-4-[(tert-butyldiphenylsilyl)oxy]-1- (ethoxycarbonyloxy)-2-cyclopentene (9) with N3-benzoylthymine and -uracil gave carbocyclic nucleosides 10 and 11. Subsequent Pd (O)-catalyzed reactions of N3-benzoyl-1-[(1R,4S)-4-(ethoxycarbonyloxy)-2-cyclopenten-1-yl]thymine (14) and -uracil (15) with O-benzylhydroxylamine smoothly gave the hydroxyamino-substituted carbocyclic nucleosides 16 and 17. From these nucleosides, the target compounds were prepared after deprotection or further reactions. The 2',3'-didehydro-2',3'-dideoxythymidine (D4T) analogue 20 was the most effective compound, with IC50 values of 27.3 and 34.5 μM against KB and L1210 cells in vitro. Carbocyclic analogues of uridine and cytidine (29 and 32) were less effective than 20 against both cell lines.
- Ogawa, Akira,Shuto, Satoshi,Tanaka, Motohiro,Sasaki, Takuma,Mori, Shuji,Shigeta, Shiro,Matsuda, Akira
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p. 1000 - 1005
(2007/10/03)
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- Preparation of cis-4-O-protected-2-cyclopentenol derivatives
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The present invention relates to a novel process for preparing cis-4-O-protected-substituted-2-cyclopentenol derivatives comprising, a) dissolving a 4-O-protected-2-cyclopentenone in a suitable organic solvent; and b) treating the solution with a suitable Lewis acid and a suitable reducing agent at a temperature of from about -100° C. to about 20° C. The cis-4-O-protected-substituted-2-cyclopentenol derivatives are useful intermediates in the preparation of various cyclopentanyl and cyclopentenyl purine analogs which are useful as immunosuppressants and in the preparation of various prostaglandins.
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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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- 4-Hydroxycyclopent-2-en-1-one and derivatives as chiral synthetic equivalents of cyclopentadienone in asymmetric Diels-Alder reactions
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Endo-tricyclodecadienone 8a and related annelated-cyclopentenones (8b, 20, 21a-c and 22) are synthesized in good chemical yield by a Diels-Alder reaction of 4-hydroxycyclo-pent-2-en-1-one 12a and derivatives 12b-h with an appropriate diene. These additions are considerably accelerated by Lewis catalysts, high pressure and by using water as solvent. Due to opposing steric and electronic effects the diastereofacial selectivity of the asymmetric cycloadditions is moderate. By carefully choosing the substrate and reaction conditions an acceptable π-facial selectivity can be achieved.
- Dols,Klunder,Zwanenburg
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p. 8515 - 8538
(2007/10/02)
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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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- Lipase-Catalyzed Transesterification of meso-Cyclopentane Diols
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The lipase-catalyzed transesterification of the meso-cyclopentane diols 1a - 6a with vinyl acetate in tetrahydrofuran/triethylamine in the presence of lipases of different origin has been investigated.Depending on the structure of the substrate and the origin of the lipase chiral cyclopentane derivatives with high enantiomeric excess could be obtained in good to excellent chemical yields. Key words: Lipase-catalyzed transesterifications; meso-cyclopentane diols; enantioselective acetylation; enzymes in organic solvents
- Theil, Fritz,Schick, Hans,Winter, Gabriele,Reck, Guenter
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p. 7569 - 7582
(2007/10/02)
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- Facile synthesis of (+)-Brefeldin A
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(+)-Brefeldin A (1) was synthesized by using (+)-4-cyanomethylcyclopent-2-en-1-one (2) as a key compound. 4-Hydroxy-2-enoate functionality was built by the reaction of the aldehyde (7) with (S)-ethyl p-chlorophenylsulfinylacetate.
- Nokami,Ohkura,Dan-Oh,Sakamoto
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p. 2409 - 1412
(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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- Vitamin B12, a Catalyst in the Synthesis of Prostaglandins
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A prostaglandin F2α precursor containing all structural features from C6 to C20 with 8R,9S, 11R and 12R chirality is obtained by the one step formation of two C-C bonds in the B12-catalyzed radical cyclization-addition sequence starting from a chiral cyclopentene bromoacetal and 1-octyne-3-one.The B12-catalyzed radical cyclization-elimination sequence of a chiral cyclopentene precursor leads to (-)-(3aR,6aS)-3,3a,6,6a-tetrahydro-2H-cyclopentafuran-2-one.Its (+)-(3aS,6aR)-enantiomer is obtained via B12-catalyzed, enantioselective isomerization of cyclopentene oxide to (R)-2-cyclopentene-1-ol followed by the B12-catalyzed cyclization-elimination sequence of its bromoacetal.
- Busato, Stephan,Tinembart, Olivier,Zhang, Zhong-da,Scheffold, Rolf
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p. 3155 - 3166
(2007/10/02)
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- A Facile Chemoenzymatic Route to Optically Pure Building Blocks for Cyclopentanoid Natural Products
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Compound (1R,4S)-(4a), a central chiral building block for cyclopentanoid natural products, was prepared in high yield and optically pure by enantioselective hydrolysis of (5a) in the presence of several lipases, and was further transformed into (R)-(1a), (1R,5S)- and (1S,5R)-(2), (7), and (8), important synthons for this class of compounds.
- Laumen, Kurt,Schneider, Manfred P.
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p. 1298 - 1299
(2007/10/02)
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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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