- Highly Reactive and Tracelessly Cleavable Cysteine-Specific Modification of Proteins via 4-Substituted Cyclopentenone
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A rapid and cysteine-specific modification of proteins using 4-substituted cyclopentenone via a Michael addition tandem elimination reaction was developed. Compared to the classical method, this reaction featured fast kinetics with a stable product. More importantly, this conjugation could be tracelessly removed by exchange with a Michael addition donor. The conjugation and regeneration process not only exhibited little change to the structures or conformations of the proteins but also exhibited little disturbance to their biological functions, such as their enzymatic activities.
- Yu, Jian,Yang, Xiaoyue,Sun, Yang,Yin, Zheng
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supporting information
p. 11598 - 11602
(2018/09/10)
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- Synthesis of 6-Substituted 2-Pyrones Starting from Renewable Resources: Total Synthesis of Sibirinone, (E)-6-(Pent-1-en-1-yl)-2H-pyran-2-one, and (E)-6-(Hept-1-en-1-yl)-2H-pyran-2-one
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An atom-economic reaction sequence to 6-substituted 2-pyrones was developed starting from furfuryl alcohol, a renewable resource made from bran or bagasse, and aldehydes, utilizing a thermal rearrangement of cyclopentadienone epoxides as key step. Derivatives bearing a hydroxyalkyl side chain could be enzymatically resolved, providing access to enantiomerically pure 2-pyrones, or converted to alkenyl-substituted 2-pyrones such as naturally occurring sibirinone, (E)-6-(pent-1-en-1-yl)-2H-pyran-2-one, and (E)-6-(hept-1-en-1-yl)-2H-pyran-2-one.
- Dobler, Daniel,Reiser, Oliver
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p. 10357 - 10365
(2016/11/17)
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- 4-Heterosubstituted Cyclopentenone Antiviral Compounds: Synthesis, Mechanism, and Antiviral Evaluation
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Racemic 4-oxocyclopent-2-en-1-yl acetate was used in a short synthesis of nucleoside analogues with pyrimidine and purine heterobases. The protocol is based on a typical nucleophilic substitution process. Uracil, thymine, 6-chloropurine, and some adenines gave the expected 4-heterosubstituted products along with the isomeric 2-heterosubstituted compounds as minor components. Samples of selected products were evaluated for their antiviral activity in a primary screening against a variety of viruses belonging to different classes. One of the compounds was found to be highly active against human papilloma virus (HPV).
- Mantione, Daniele,Aizpuru, Olatz Olaizola,Memeo, Misal Giuseppe,Bovio, Bruna,Quadrelli, Paolo
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p. 983 - 991
(2016/03/01)
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- The thio-adduct facilitated, enzymatic kinetic resolution of 4-hydroxycyclopentenone and 4-hydroxycyclohexenone
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The addition of 3,4-dimethoxybenzyl thiol 8, as a benzyl thiol surrogate, to racemic 4-hydroxycyclopent-2-enone 2 and 4-hydroxycyclohex-2-enone 15 gave the corresponding cis-adducts (±)-3-(3,4-dimethoxybenzylthio)-4- hydroxycyclopentanone 4b and (±)-3-(3,4-dimethoxybenzylthio)-4- hydroxycyclohexanone 16 with good diastereocontrol. In both cases, subsequent treatment with vinyl acetate, in the presence of a lipase enabled enantiomer resolution. Thus, (+)-16 and the acetate of its enantiomer, (-)-(1R,2S)-2-(3,4- dimethoxybenzylthio)-4-oxocyclohexyl acetate, (-)-17 were isolated in 98% enantiomeric excess. Based on the 1,4-dioxygenation pattern, (-)-17 can be used to prepare both enantiomers of 4-(tert-butyldimethylsilyloxy)cyclohex-2-enone 19. Firstly, saponification, with a sub-stoichiometric amount of NaOMe, followed by a one-pot silyl ether formation-sulfide elimination sequence gave (+)-19. Then using the same starting material a 6-step sequence, featuring a diastereoselective NaBH4 reduction and a Cope-type sulfoxide elimination, gave (-)-19.
- O'Byrne, Aisling,Murray, Cian,Keegan, Dearbhla,Palacio, Carole,Evans, Paul,Morgan, Ben S.
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scheme or table
p. 539 - 545
(2010/05/11)
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- Enzymatic kinetic resolution studies of racemic 4-hydroxycyclopent-2-en- 1-one using Lipozyme IM
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Enzymatic kinetic resolution studies of (±)-4-hydroxycyclopent-2-en-1- one 2 were taken up in organic solvents by transesterification with vinyl acetate and alcoholysis of its acetate 3 as an alternative to the desymmetrization of meso-cyclopentenediol to provide faster and economic access to enantiomerically pure 4-(R)-tert-butyldimethylsilyloxycyclopent-2- en-1-one 1. Parameters were screened using Lipozyme IM as catalyst. Although enantioselectivity observed was moderate (E=24, by alcoholysis of 3 with 2-butanol), trends in the effect of solvent, water content and alcohol structure showed useful directions for screening of other enzymes for optimization of the method to useful levels of efficiency.
- Ghorpade, Sandeep R.,Bastawade, Kulbhushan B.,Gokhale, Digambar V.,Shinde, Popat D.,Mahajan, Vishal A.,Kalkote, Uttam R.,Ravindranathan
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p. 4115 - 4122
(2007/10/03)
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- Organic reactions in the solid state: Reactions of enclathrated 3,4- epoxycyclopentanone (= 6-oxobicyclo[3.1.0]hexan-3-one) in Tri-othymotide and absolute configuration of 4-hydroxy- and 4-chlorocyclopent-2-en-1-one
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Several aspects of the heterogeneous actions of aqueous and gaseous HCl on the chemical behavior of 3,4-epoxycyclopentanone (=6- oxablcyclo[3.1.0]hexan-3-one; 1) included in the asymmetric cages of tri-o- thymotide (TOT) clathrates belonging to space groups P3121 are described, showing specific features strikingly at variance with those observed in liquid solutions. In a first step, the substrate underwent an acid-promoted allylic isomerization, as already observed in our previous investigations, to give optically active 4-hydroxycydopent-2-en-1-one (2). In a Consecutive step, a displacement of the OH group was accomplished by the Cl- anion to afford the corresponding chloro compound 3. Polymorphism was encountered in the preparation of TOT/1 clathrates. Recrystallization of TOT in the pure guest 1 yielded micro-twinned crystals belonging to the P31 space group (host/guest ratio 1: 1), whereas the expected P3121 lattice grew from a mixture of TOT, 1 and MeOH. The structural determination of TOT/1 was carried out by X-ray diffraction (Fig. 1). Kinetic measurements were achieved that shed light on some striking features of this type of heterogeneous reactions for solid-liquid and solid-gas systems. Several reactions of pure clathrate antipodes (+)-TOT/1 with gaseous HCl were carried out under various conditions; concentration and enantiomer-excess(ee) determinations of the products 2 and 3 allowed to establish a larger ee for 3, thus demonstrating the influence of the host-guest diastereomeric association on the progression of the reaction. The correlation of optical activities of the host and products for the global reaction disclosed the sequence (+)-(M)-TOT/1 → (- )-2 → (-)-3. A new way for the preparation of 2 was devised. It was further demonstrated that the X-ray structure analysis of the chiral clathrate (M)- TOT/(+)-2 (Fig. 4) associated with chitoptical measurements was an efficient and straightforward method to determine the absolute (+)-(R)-configuration of the guest. The enantioselectivity of the TOT clathrate for 2 was established by two different methods which allowed the appraisal of an accurate revised value of the specific rotation of 2. The enclathration of 3 occurred exclusively in the orthorhombic centrosymmetric host lattice Pbca, thus prohibiting the X-ray structural determination of the guest absolute configuration. The problem of finding a pathway to the intended enantiomer enrichment of 3 was worked out through the action of aqueous HCI on microcrystalline (+)-TOT/(-)-(S)-2 that gave an optically active mixture of unreacted 2 with 3 as sole product. The pure optically active 3 was isolated by Subsequent TLC. The resolution of 3 was achieved by GC over a chiral column and its (unknown) specific rotation measured. The absolute configuration of 3 was established by the measurement of the enantiomer purity of the optically active mixture 3 obtained after the total conversion of (-)-(S)-2 in the presence of thionyl chloride in Et2O, dioxane, and benzene. It was deduced that the (-)-3 enantiomer had the (S)-configuration.
- Gerdil, Raymond,Liu, Huiyou,Bernardinelli, Gerald
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p. 418 - 434
(2007/10/03)
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- An Efficient Synthesis of 4(S)-Hydroxycyclopent-2-enone
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An efficient synthesis of 4(S)-hydroxycyclopent-2-enone of high optical purity, a key synthon used in natural product synthesis, is described.The method is suitable for large-scale synthesis.
- Khanapure, Subhash P.,Najafi, Nahid,Manna, Sukumar,Yang, Jing-Jing,Rokach, Joshua
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p. 7548 - 7551
(2007/10/03)
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- A New Resolution Procedure for the Preparation of Both (R)-(+)- and (S)-(-)-4-tert-Butoxycyclopent-2-enone from Racemic 4-tert-Butoxycyclopent-2-enone and Conversion of (R)-(+)-Butoxycyclopent-2-enone into (R)-(+)-4-Acetoxycyclopent-2-enone. A New Method for the Determination of the ...
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(1S)-(-)-10-Mercaptoisoborneol undergoes conjugate addition to (+/-)-4-tert-butoxycyclopent-2-enone in methanol containing N,N,N',N'-tetramethylethylenediamine to give a 1:1 mixture of diastereomers of 3-tert-butoxy-4-heptanyl)methyl>thio>cyclopentanone in 93-95percent yield.The mixture is converted by m-chloroperbenzoic acid into the corresponding sulfoxide mixture.The (3R,4R,RS)-sulfoxide isomer, whose absolute configuration has been determined by X-ray crystallography, crystallizes cleanly from this mixture in an enantiomeric yield of 76percent from the corresponding sulfide.It is decomposed on silica gel to generate (R)-(+)-4-tert-butoxycyclopent-2-enone, with an enantiomeric purity of >/- 99.9percent in 92percent yield from the sulfoxide, and 10-thiodiisobornyl 10'-sulfoxide.Similarly, the (S)-(-)-enone is prepared from (1R)-(+)-10-mercaptoisoborneol.The (+/-) and the (R)-(+)-enone, respectively, are converted by a catalytic amount of FeCl3 in acetic anhydride into (+/-) and (R)-(+)-4-acetoxycyclopent-2-enone (with an enantiomeric purity of >/- 99.9percent) in 80percent yield.The enantiomeric purity of the products was assessed through their treatment with (-)-10-mercaptoisoborneol and analysis of the adducts by HPLC and 400-MHz 1H NMR spectroscopy.
- Eschler, Bart M.,Haynes, Richard K.,Ironside, Michael D.,Kremmydas, Steve,Ridley, Damon D.,Hambley, Trevor W.
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p. 4760 - 4766
(2007/10/02)
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- SYNTHESIS OF PUNAGLANDIN 4 BY MEANS OF ENZYMATIC RESOLUTION OF THE KEY CHLOROCYCLOPENTENE DERIVATIVE
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Punaglandin 4, a chlorinated marine prostanoid, was synthesized starting from two chiral building blocks, (+)-tartaric acid and (1S, 4R)-(-)-4-t-butyldimethylsilyloxy-3-chloro-2-cyclopenten-1-ol, which was prepared by asymmetric hydrolysis of the correspo
- Mori, Kenji,Takeuchi, Tadashi
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p. 333 - 342
(2007/10/02)
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- Process for the preparation of 4-hydroxycyclopent-2-en-1-one derivatives
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Novel optically active compounds of 4-protected hydroxy-cyclopent-2-en-1-ones of the formula STR1 wherein R is a splittable protective group for an alcoholic hydroxyl group, and a process for preparing the 4-protected hydroxycyclopent-2-en-1-ones by oxidizing monohydroxy-protected derivatives of cyclopent-1-ene-3,5-diol expressed by the following formula STR2 wherein R is the same as defined above. Optically active 4-hydroxycyclopent-2-en-1-one which is an optically active isomer of the compound of formula (2); or optically active cyclopent-1-en-3,5-diol (R-isomer) and a novel diacyl derivative of the diol, a novel monoacylmonosilyl-derivative of the diol and a novel monoacylmonotetrahydropyranol-derivative of the diol, which are intermediates for the protective derivative of formula (1). Processes are also provided for preparing the protective derivatives of formula (1) by converting these intermediates by esterification, hydrolysis, enzymatic processes, etc. The optically active compounds of formula (2) are useful as precursors for the preparation of prostaglandin or its analogues.
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