- Total Synthesis of (+)-Guadinomic Acid via Hydroxyl-Directed Guanidylation
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Protecting-group-free total synthesis of (+)-guadinomic acid is reported using δ-valerolactone as a readily available starting material. The protocol utilizes the recent hydroxyl-directed guanidylation of unactivated alkenes as an approach for direct stereoselective incorporation of the guanidine unit furnishing the natural product in 7 steps.
- Reid, Bradley T.,Mailyan, Artur K.,Zakarian, Armen
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- Molecular design of diene monomers containing an ester functional group for the synthesis of poly(diene sulfone)s by radical alternating copolymerization with sulfur dioxide
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Functional poly(diene sulfone)s are prepared by the radical alternating copolymerization of 1,3-diene monomers containing an ester substituent with sulfur dioxide. Methyl 3,5-hexadienoate (MH) and methyl 5,7-octadienoate (MO) with both an alkylene spacer and a terminal diene structure are suitable to produce a high-molecular-weight copolymer in a high yield, while the copolymerization of 5,7-nonadienoic acid, ethyl 2,4-pentadienoate, and ethyl 4-methyl-2,4-pentadienoate including either an alkylene spacer or a terminal diene structure lead to unsuccessful results. The 13C NMR chemical shift values of MH and MO suggest a high electron density at their reacting α-carbon for exhibiting a high copolymerization reactivity. Fluorene-containing diene monomers, 9-fluorenyl 3,5-hexadienoate (FH) and 9-fluorenyl 5,7-octadienoate (FO), are also prepared and copolymerized with sulfur dioxide. The thermal and optical properties of the poly(diene sulfone)s containing the methyl and fluorenyl ester substituents in the side chain are investigated.
- Matsumoto, Akikazu,Lee, Sungi,Okamura, Haruyuki
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- Structure-activity relationship study of flowering-inducer FN against Lemna paucicostata
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FN1 (1) and FN2 (2), cycloadducts of α-ketol octadecadienoic acid (3) with norepinephrine (NE), induce flowering in Lemna paucicostata. In order to broaden our understanding of structural requirements of FN?for flower induction, nine analogs of 3 (4-12) were synthesized and reacted with NE under basic conditions. These analogs, except for 8, 10, and 12, exhibited significant activity regarding to floral induction in L. paucicostata. Similar experiments were carried out by using 3 and epinephrine, and it was demonstrated that these products also possessed biological activity.
- Kai, Kenji,Takeuchi, Jun,Kataoka, Taichi,Yokoyama, Mineyuki,Watanabe, Naoharu
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- Photocurable hard and porous biomaterials from ROMP precursors cross-linked with diyl radicals
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A combination of (ROMP) ring-opening metathesis polymerization and diradical (diyl) cross-linking provides a new access to hard biomaterials and potential artificial bone replacements. ROMP was used to construct soft and pliable linear polymers bearing photolabile diazene functions. After treatment with light, a nitrogen aerosol is released throughout the polymer to create desirable porosity, cross-linking, and hardening in a single step. Nonpolymeric mechanistic work supporting these studies was also examined.
- Enholm, Eric,Joshi, Aarti,Wright, Dennis L.
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- A convenient and mild procedure for the preparation of hydroxyesters from lactones and hydroxyacids
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An alcoholic solution of lactones and hydroxyacids stored on Amberlyst-15 results in the formation of corresponding hydroxyesters in high yields.
- Anand,Selvapalam
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Read Online
- Catalytic asymmetric synthesis of Leukotriene B4
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Leukotriene B4 1 was prepared from two chiral synthons 8 and 14. The chiral secondary alcohols of 8 and 14 were constructed by BINOL/Ti(OiPr)4 catalyzed enantioselective alkynylzinc addition to aldehydes.
- Yang, Pengfei,Zhong, Jiangchun,Ji, Kaijie,Yin, Jingwei,Li, Shuoning,Wei, Siyuan,Zhou, Yun,Wang, Lifeng,Wang, Min,Bian, Qinghua
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- Mechanism-based inactivation of serine proteases by dichlorocyclopropane fused lactone derivatives
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A dichlorocyclopropane fused lactone derivative was prepared as a novel mechanism-based inactivator of serine protease, α-chymotrypsin. The lactone derivative showed transient irreversible inhibitory activity toward α-chymotrypsin with the value of k(obsd)/[I] = 54 M-1s-1 and the enzyme activity recovered perfectly after 6 hours.
- Ohba, Tsuyoshi,Ikeda, Eitatsu,Tsuchiya, Naoki,Nishimura, Kuniko,Takei, Hisashi
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- Oxidation of cyclic acetals by ozone in ionic liquid media
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The application of ozone-stable pyrrolidinium based ionic liquids as safe reaction media resulted in selective hydroxy ester formation upon ozonation of cyclic acetals without using low temperatures or acetylating reagents.
- Van Doorslaer, Charlie,Peeters, Annelies,Mertens, Pascal,Vinckier, Chris,Binnemans, Koen,De Vos, Dirk
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- Kinetic analysis of terminal and unactivated C-H bond oxyfunctionalization in fatty acid methyl esters by monooxygenase-based whole-cell biocatalysis
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The alkane monooxygenase AlkBGT from Pseudomonas putida GPo1 constitutes a versatile enzyme system for the ω-oxyfunctionalization of medium chain-length alkanes. In this study, recombinant Escherichia coli W3110 expressing alkBGT was investigated as whole-cell catalyst for the regioselective biooxidation of fatty acid methyl esters to terminal alcohols. The ω-functionalized products are of general economic interest, serving as building blocks for polymer synthesis. The whole-cell catalysts proved to functionalize fatty acid methyl esters with a medium length alkyl chain specifically at the ω-position. The highest specific hydroxylation activity of 104 U gCDW-1 was obtained with nonanoic acid methyl ester as substrate using resting cells of E. coli W3110 (pBT10). In an optimized set-up, maximal 9-hydroxynonanoic acid methyl ester yields of 95% were achieved. For this specific substrate, apparent whole-cell kinetic parameters were determined with a Vmax of 204±9 U gCDW -1, a substrate uptake constant (KS) of 142±17 μM, and a specificity constant Vmax/KS of 1.4 U g CDW-1 μM-1 for the formation of the terminal alcohol. The same E. coli strain carrying additional alk genes showed a different substrate selectivity. A comparison of biocatalysis with whole cells and enriched enzyme preparations showed that both substrate availability and enzyme specificity control the efficiency of the whole-cell bioconversion of the longer and more hydrophobic substrate dodecanoic acid methyl ester. The efficient coupling of redox cofactor oxidation and product formation, as determined in vitro, combined with the high in vivo activities make E. coli W3110 (pBT10) a promising biocatalyst for the preparative synthesis of terminally functionalized fatty acid methyl esters. Copyright
- Schrewe, Manfred,Magnusson, Anders O.,Willrodt, Christian,Buehler, Bruno,Schmid, Andreas
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- Enantioselective Total Synthesis of (+)-Heilonine
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Chemical transformations that rapidly and efficiently construct a high level of molecular complexity in a single step are perhaps the most valuable in total synthesis. Among such transformations is the transition metal catalyzed [2 + 2 + 2] cycloisomerization reaction, which forges three new C-C bonds and one or more rings in a single synthetic operation. We report here a strategy that leverages this transformation to open de novo access to the Veratrum family of alkaloids. The highly convergent approach described herein includes (i) the enantioselective synthesis of a diyne fragment containing the steroidal A/B rings, (ii) the asymmetric synthesis of a propargyl-substituted piperidinone (F ring) unit, (iii) the high-yielding union of the above fragments, and (iv) the intramolecular [2 + 2 + 2] cycloisomerization reaction of the resulting carbon framework to construct in a single step the remaining three rings (C/D/E) of the hexacyclic cevanine skeleton. Efficient late-stage maneuvers culminated in the first total synthesis of heilonine (1), achieved in 21 steps starting from ethyl vinyl ketone.
- Cassaidy, Kyle J.,Rawal, Viresh H.
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supporting information
p. 16394 - 16400
(2021/10/20)
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- Site-Selective 1,1-Difunctionalization of Unactivated Alkenes Enabled by Cationic Palladium Catalysis
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A palladium(II)-catalyzed 1,1-difunctionalization of unactivated terminal and internal alkenes via addition of two nucleophiles was developed using a cationic palladium(II) complex. The palladacycle generated in situ as a result of a regioselective addition of a nucleophile to the alkene can readily undergo regioselective β-hydride elimination and migratory insertion with a cationic palladium catalyst. The resulting η3-π-allyl palladium(II) complex is the key intermediate that reacts with a second nucleophile to furnish the desired 1,1-difunctionalization of the alkene. Under the optimized reaction conditions, a wide range of indoles and anilines add to alkene units of 3-butenoic or 4-pentenoic acid derivatives to afford the synthetically useful γ,γ- or δ,δ-difunctionalized products with excellent regiocontrol. Furthermore, by employing internal hydroxyl or acid groups and external carbon nucleophiles, this transformation enables unsymmetric 1,1-difunctionalization to forge challenging and important oxo quaternary carbon centers. Combining experiments and DFT calculations on the mechanism of the reaction is investigated in detail.
- Jeon, Jinwon,Ryu, Ho,Lee, Changseok,Cho, Dasol,Baik, Mu-Hyun,Hong, Sungwoo
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supporting information
(2019/07/03)
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- Site-Selective 1,1-Difunctionalization of Unactivated Alkenes Enabled by Cationic Palladium Catalysis
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A palladium(II)-catalyzed 1,1-difunctionalization of unactivated terminal and internal alkenes via addition of two nucleophiles was developed using a cationic palladium(II) complex. The palladacycle generated in situ as a result of a regioselective addition of a nucleophile to the alkene can readily undergo regioselective β-hydride elimination and migratory insertion with a cationic palladium catalyst. The resulting η 3-π-allyl palladium(II) complex is the key intermediate that reacts with a second nucleophile to furnish the desired 1,1-difunctionalization of the alkene. Under the optimized reaction conditions, a wide range of indoles and anilines add to alkene units of 3-butenoic or 4-pentenoic acid derivatives to afford the synthetically useful γ,γ-or ?,?-difunctionalized products with excellent regiocontrol. Furthermore, by employing internal hydroxyl or acid groups and external carbon nucleophiles, this transformation enables unsymmetric 1,1-difunctionalization to forge challenging and important oxo quaternary carbon centers. Combining experiments and DFT calculations on the mechanism of the reaction is investigated in detail.
- Jeon, Jinwon,Ryu, Ho,Lee, Changseok,Cho, Dasol,Baik, Mu-Hyun,Hong, Sungwoo
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supporting information
p. 10048 - 10059
(2019/07/04)
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- PYRAZOLE DERIVATIVES AS NHIBITORS OF THE WNT SIGNALLING PATHWAY
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The present invention relates to a novel class of compounds as inhibitors of the Wnt signalling pathway. The best compounds showed potencies in the low micromolar range and high efficacies (> 80%) together with good microsomal stability. Furthermore, in v
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Page/Page column 6; 34
(2019/09/18)
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- Selective hydrogenolysis of 2-furancarboxylic acid to 5-hydroxyvaleric acid derivatives over supported platinum catalysts
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The conversion of 2-furancarboxylic acid (FCA), which is produced by oxidation of furfural, to 5-hydroxyvaleric acid (5-HVA) and its ester/lactone derivatives with H2 was investigated. Monometallic Pt catalysts were effective, and other noble metals were not effective due to the formation of ring-hydrogenation products. Supports and solvents had a small effect on the performance; however, Pt/Al2O3 was the best catalyst and short chain alcohols such as methanol were better solvents. The optimum reaction temperature was about 373 K, and at higher temperature the catalyst was drastically deactivated by deposition of organic materials on the catalyst. The highest yield of target products (5-HVA, δ-valerolactone (DVL), and methyl 5-hydroxyvalerate) was 62%, mainly obtained as methyl 5-hydroxyvalerate (55% yield). The byproducts were mainly ring-hydrogenation compounds (tetrahydrofuran-2-carboxylic acid and its ester) and undetected ones (loss of carbon balance). The catalyst was gradually deactivated during reuses even at a reaction temperature of 373 K; however, the catalytic activity was recovered by calcination at 573 K. The reactions of various related substrates were carried out, and it was found that the O-C bond in the O-CC structure (1,2,3-position of the furan ring) is dissociated before CC hydrogenation while the presence and position of the carboxyl group (or methoxy carbonyl group) much affect the reactivity.
- Asano, Takehiro,Takagi, Hiroshi,Nakagawa, Yoshinao,Tamura, Masazumi,Tomishige, Keiichi
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supporting information
p. 6133 - 6145
(2019/11/20)
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- Dynamic kinetic resolution of 2-methyl-2-nitrocyclohexanol: Combining the intramolecular nitroaldol (Henry) reaction & lipase-catalysed resolution
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Efforts to combine the intramolecular nitroaldol reaction with lipase-catalysed resolution of the resulting nitroaldol adduct in a one-pot dynamic kinetic resolution (DKR) are described. Significant challenges were encountered in the combination of the two systems. trans-2-Methyl-2-nitrocyclohexyl acetate (±)-3b was isolated in excellent enantiopurity (>98% ee) via a sequential DKR sequence where the lipase-mediated resolution and base-mediated interconversion of 2-methyl-2-nitrocyclohexanol 2 were effected alternately, demonstrating the feasibility of this approach initially. Further work showed, for the first time, evidence that a DKR-type system is possible for 2. Reaction engineering allowed the design of a sequential one-pot reaction system which furnished the products with excellent enantioselectivity, and good diastereoselectivity.
- Foley, Aoife M.,Gavin, Declan P.,Deasy, Rebecca E.,Milner, Sinéad E.,Moody, Thomas S.,Eccles, Kevin S.,Lawrence, Simon E.,Maguire, Anita R.
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p. 1435 - 1443
(2018/02/23)
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- One-pot chemoenzymatic synthesis of trolline and tetrahydroisoquinoline analogues
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Chemoenzymatic reaction cascades can provide access to chiral compounds from low-cost starting materials in one pot. Here we describe one-pot asymmetric routes to tetrahydroisoquinoline alkaloids (THIAs) using the Pictet-Spenglerase norcoclaurine synthase (NCS) followed by a cyclisation, to give alkaloids with two new heterocyclic rings. These reactions operated with a high atom economy to generate THIAs in high yields.
- Zhao, Jianxiong,Lichman, Benjamin R.,Ward, John M.,Hailes, Helen C.
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supporting information
p. 1323 - 1326
(2018/02/14)
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- Method of utilizing bifunctional catalyst to prepare methyl 5-hydroxypentanoate
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The invention discloses a method of utilizing a bifunctional catalyst to prepare methyl 5-hydroxypentanoate. According to the method, a Zn-Ce-TiO2 catalyst is used to replace precious metals such as Rh, Au, and the like. Two steps of preparing semi-furfural methanol from furfural and preparing methyl furoate from semi-furfural methanol are efficiently carried out in a same reactor in the presenceof a catalyst. The catalyst cost is reduced, at the same time, the intermediate (semi-furfural methanol) is dehydrogenized and converted into methyl furoate, the reaction temperature is reduced, the polymerization side reactions are avoided, and high selectivity of methyl furoate is maintained.
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Paragraph 0032; 0033
(2019/01/05)
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- A process for manufacturing a δ - e lactone method (by machine translation)
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The invention provides a method for manufacturing δ - e lactone of the new method. The method comprises: 1) type (I) acetic acid alkyl esters with epichlorohydrin undergo nucleophilic substitution reaction, of formula (III) 4, 5 - epoxy valeric acid alkyl ester; 2) step 1) of formula (III) of 4, 5 - epoxy valeric acid alkyl ester hydrogenation reaction of formula (IV) 5 - hydroxy valeric acid alkyl ester; 3) steps 2) of formula (IV) of the 5 - hydroxy valeric acid alkyl ester generate the cyclization reaction generating δ - e lactone. The method of the invention total reaction yield up to 95% or more. The method the raw material is cheap, small pollution to the environment, mild reaction conditions, low cost, high yield of products to be easily purified, is suitable for industrial production. (by machine translation)
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Paragraph 0060; 0062-0065; 0086-0089; 0098
(2018/05/30)
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- Preparation method of 5-methyl hydroxyvalerate
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The invention discloses a preparation method of 5-methyl hydroxyvalerate. According to the preparation method, a Cu-La-Al2O3 catalyst is taken as a catalyst for replacing heavy metals of Rh and Au, and the two-step reaction for preparing furfural hemimeth
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Paragraph 0036-0037
(2018/12/02)
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- CYCLIC PHOSPHATE SUBSTITUTED NUCLEOSIDE COMPOUNDS AND METHODS OF USE THEREOF FOR THE TREATMENT OF VIRAL DISEASES
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The present invention relates to Cyclic Phosphate Substituted Nucleoside Compounds of Formula (I), and pharmaceutically acceptable salts thereof, wherein A, B, R1, R2, R3, Q and V are as defined herein. The present invention also relates to compositions comprising a Cyclic Phosphate Substituted Nucleoside Compound, and methods of using the Cyclic Phosphate Substituted Nucleoside Compounds for treating or preventing HCV infection in a patient.
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(2018/04/12)
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- Microwave-Assisted Synthesis of Heterocycles by Rhodium(III)-Catalyzed Annulation of N-Methoxyamides with α-Chloroaldehydes
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α-Chloroaldehydes have been used as alkyne equivalents in rhodium-catalyzed syntheses of isoquinolones and 3,4-dihydroisoquinolins starting from N-methoxyamides. Compared to the existing technology, a complementary regioselectivity is achieved. Mechanistic investigations have been performed, and it was found that steric effects of both substrate and additive determine the product selectivity. Various other heterocycles, such as isoquinolines and lactones, can be prepared by transformation of the obtained products.
- Huang, Ji-Rong,Bolm, Carsten
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supporting information
p. 15921 - 15925
(2017/11/27)
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- Method for preparing methyl 5-hydroxypentanoate
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The invention discloses a method for preparing methyl 5-hydroxypentanoate. The method adopts a brand new technologic route and uses renewable biomass furfural with wide use sources as a raw material, and a reaction of furfural and methanol to generate fur
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Page/Page column 0016; 0048-0057; 0061
(2017/09/02)
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- Asymmetric synthesis of 12-hydroxyheptadecatrienoic acid and its 5,6-dihydro- and 14,15-dehydro-derivatives
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Natural 12-hydroxyheptadecatrienoic acid (12-HHT) with an S configuration was synthesised by a Suzuki-Miyaura coupling of C10-C17 iodo alcohol with C1-C9 vinylborane. The iodo alcohol was synthesised by utilising Sharpless asymmetric epoxidation of the corresponding trimethylsilyl alcohol. The method yielded more than 100 mg of 12-HHT. Similarly, syntheses of 5,6-dihydro- and 14,15-dehydro derivatives of 12-HHT, known as HHD and HHTE, respectively, were completed in a stereoselective manner.
- Kobayashi, Yuichi,Morita, Masao,Ogawa, Narihito,Kondo, Daiki,Tojo, Toshifumi
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p. 10667 - 10673
(2016/11/30)
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- Stereoselective synthesis of epoxyisoprostanes: an organocatalytic and "pot-economy" approach
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An efficient and direct synthetic route to epoxyisoprostane EC methyl ester has been accomplished in 8 steps (10% overall yield) from readily available starting materials using a series of asymmetric organocatalytic reactions and one-pot operations.
- Weng, Jiang,Wang, Sheng,Huang, Lin-Jie,Luo, Zhang-Yi,Lu, Gui
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supporting information
p. 10170 - 10173
(2015/06/22)
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- A Domino Diels-Alder Approach toward the Tetracyclic Nicandrenone Framework
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The tetracarbocyclic framework of the nicandrenone natural products is formed in one step from a linear precursor via a domino intramolecular Diels-Alder/intramolecular furan Diels-Alder/aromatization sequence. The approach represents a new 0 → ABCD strategy for the preparation of aromatic steroids.
- MacKay, Emily G.,N?rret, Marck,Wong, Leon S.-M.,Louis, Ignace,Lawrence, Andrew L.,Willis, Anthony C.,Sherburn, Michael S.
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supporting information
p. 5517 - 5519
(2015/12/23)
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- Chroman-4-one- and chromone-based sirtuin 2 inhibitors with antiproliferative properties in cancer cells
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Sirtuins (SIRTs) catalyze the NAD+-dependent deacetylation of Nε-acetyl lysines on various protein substrates. SIRTs are interesting drug targets as they are considered to be related to important pathologies such as inflammation and aging-associated diseases. We have previously shown that chroman-4-ones act as potent and selective inhibitors of SIRT2. Herein we report novel chroman-4-one and chromone-based SIRT2 inhibitors containing various heterofunctionalities to improve pharmacokinetic properties. The compounds retained both high SIRT2 selectivity and potent inhibitory activity. Two compounds were tested for their antiproliferative effects in breast cancer (MCF-7) and lung carcinoma (A549) cell lines. Both compounds showed antiproliferative effects correlating with their SIRT2 inhibition potency. They also increased the acetylation level of α-tubulin, indicating that SIRT2 is likely to be the target in cancer cells. A binding mode of the inhibitors that is consistent with the SAR data was proposed based on a homology model of SIRT2.
- Seifert, Tina,Malo, Marcus,Kokkola, Tarja,Engen, Karin,Fridén-Saxin, Maria,Wallén, Erik A. A.,Lahtela-Kakkonen, Maija,Jarho, Elina M.,Luthman, Kristina
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p. 9870 - 9888
(2015/02/05)
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- CARBOHYDRATE CONJUGATED RNA AGENTS AND PROCESS FOR THEIR PREPARATION
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This disclosure relates to an improved process for the preparation of carbohydrate conjugates. The disclosure also relates to carbohydrate conjugated iRNA agents comprising these carbohydrate conjugates, which have improved purity and are advantageous for the in vivo delivery of the iRNA agents.
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Page/Page column 42; 43; 63; 64
(2014/03/21)
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- SMALL MOLECULE COMPOUNDS FOR THE CONTROL OF NEMATODES
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The present invention relates to compounds involved in nematode signaling.
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Paragraph 0416; 0417
(2013/03/26)
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- Study of the total synthesis of (-)-exiguolide
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In this article, we disclose the various routes and strategies we had to explore before finally achieving the total synthesis of (-)-exiguolide ((-)-1). Two first types of approaches were set, both relying on the Trost's domino ene-yne coupling/oxa-Michael reaction that we choose for its ability to control the geometry of the methylacrylate-bearing tetrahydropyrane ring B. In our first approach, we expected to assemble the two main fragments (C14-C21 and C1-C13) by creating the C13-C14 bond through a palladium(0)-catalyzed cross-coupling, but this step failed, unfortunately. In the second approach, which was more linear, we created the C16-C17 bond through condensation of a lithium acetylide on a Weinreb amide, and we assembled the C1-C5 and C6-C21 subunits through Trost's domino ene-yne coupling/oxa-Michael reaction. These two approaches served us to design an ameliorated third strategy, which finally led to the total synthesis of (-)-exiguolide.
- Cook, Cyril,Liron, Frederic,Guinchard, Xavier,Roulland, Emmanuel
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experimental part
p. 6728 - 6742
(2012/09/21)
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- Catalysis-based and protecting-group-free total syntheses of the marine oxylipins hybridalactone and the ecklonialactones A, B, and C
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Concise and protecting-group-free total syntheses of the marine oxylipins hybridalactone (1) and three members of the ecklonialactone family (2-4) were developed. They deliver these targets in optically pure form in 14 or 13 steps, respectively, in the longest linear sequence; five of these steps are metal-catalyzed and four others are metal-mediated. The route to either 1 or 2-4 diverges from the common building block 22, which is accessible in 7 steps from 2[5H]furanone by recourse to a rhodium-catalyzed asymmetric 1,4-addition reaction controlled by the carvone-derived diene ligand 35 and a ring-closing alkene metathesis (RCM) catalyzed by the ruthenium indenylidene complex 17 as the key operations. Alternatively, 22 can be made in 10 steps from furfural via a diastereoselective three-component coupling process. The further elaboration of 22 into hybridalactone as the structurally most complex target with seven contiguous chiral centers was based upon a sequence of cyclopropanation followed by a vanadium-catalyzed epoxidation, both of which were directed by the same free hydroxy group at C15. The macrocyclic scaffold was annulated to the headgroup by means of a ring-closing alkyne metathesis reaction (RCAM). In response to the unusually high propensity of the oxirane of the targeted oxylipins for ring opening, this transformation had to be performed with complexes of the type [(Ar3SiO)4Mo≡CPh] [K·OEt2] (43), which represent a new generation of exceedingly tolerant yet remarkably efficient catalysts. Their ancillary triarylsilanolate ligands temper the Lewis acidity of the molybdenum center but are not sufficiently nucleophilic to engage in the opening of the fragile epoxide ring. A final semireduction of the cycloalkyne formed in the RCAM step to the required (Z)-alkene completed the total synthesis of (-)-1. The fact that the route from the common fragment 22 to the ecklonialactones could follow a similar logic showcased the flexibility inherent to the chosen approach.
- Hickmann, Volker,Kondoh, Azusa,Gabor, Barbara,Alcarazo, Manuel,Fuerstner, Alois
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supporting information; experimental part
p. 13471 - 13480
(2011/10/10)
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- Product recovery from ionic liquids by solvent-resistant nanofiltration: Application to ozonation of acetals and methyl oleate
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In this work we tackle the problematic separation of reaction products from ionic liquid media. Solvent-resistant nanofiltration proves to be an attractive technique for the separation of non-volatile polar products from ionic liquids. In view of the high compatibility between ozone and ionic liquids, two ozone-mediated model reactions were chosen: firstly the oxidation of acetals to esters in the presence of ozone and secondly the ozonation of methyl oleate to monomethyl azelate and pelargonic acid. The objective was to retain the ionic liquid phase by means of a solvent-resistant nanofiltration membrane, while the organic reaction products permeate through the polymeric membrane. First, the ozonations were studied in order to know the characteristic product compositions. Next, a screening of membranes was performed on synthetic product mixtures. The second generation polyimide-based DuraMem membranes showed the highest rejection, up to 96%, for the evaluated ionic liquids. These DuraMem membranes also proved suitable for the separation of the products on real reaction mixtures, even in a single filtration step.
- Van Doorslaer, Charlie,Glas, Daan,Peeters, Annelies,Cano Odena, Angels,Vankelecom, Ivo,Binnemans, Koen,Mertens, Pascal,De Vos, Dirk
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experimental part
p. 1726 - 1733
(2011/02/22)
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- Method for preparing largazole analogs and uses thereof
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Analogs of largazole are described herein. Methods of treating cancer and blood disorders using largazole and largazole analogs and pharmaceutical compositions comprising the same are additionally described herein. Methods for preparing largazole analogs are likewise described.
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Page/Page column 38
(2010/03/02)
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- Algal pheromone biosynthesis: Stereochemical analysis and mechanistic implications in gametes of ectocarpus siliculosus
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During sexual reproduction, female gametes or eggs of brown algae release pheromones to attract their male mating partners. The biologically active compounds comprise linear or alicyclic unsaturated hydrocarbons derived from the aliphatic terminus of C20 polyunsaturated fatty acids (PUFAs) by oxidative cleavage. The current study addresses the stereochemical course of the pheromone biosynthesis using female gametes of the marine brown alga E. siliculosus and chiral deuterium-labeled arachidonic acids. The biosynthetic sequence is likely to proceed via an intermediary 9-hydroperoxyarachidonic acid, which is cleaved with loss of the C(16)-HR into the C 11-hydrocarbon dictyopterene C and 9-oxonona-(5Z,7E)-dienoic acid.
- Rui, Fabio,Boland, Wilhelm
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supporting information; experimental part
p. 3958 - 3964
(2010/08/22)
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- Transesterification via Baeyer-Villiger oxidation utilizing potassium peroxydisulfate (K2S2O8) in acidic media
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Baeyer-Villiger oxidation of ketones with potassium peroxydisulfate (K 2S2O8) and sulfuric acid generates the anticipated esters or lactones. These products are transformed into new esters (or hydroxy esters) in the presence of alcohols via transesterification under Baeyer-Villiger reaction conditions in one pot. Springer-Verlag 2010.
- Zarrabi,Mahmoodi,Marvi
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experimental part
p. 889 - 891
(2011/06/27)
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- ORGANIC COMPOUNDS
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The present invention provides a compound of formula (I): wherein the variants R1, R2, R3, R4, R5, R6, R7 are as defined herein, and wherein said compound is an inhibitor of CETP, and thus can be employed for the treatment of a disorder or disease mediated by CETP or responsive to the inhibition of CETP.
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Page/Page column 71
(2009/05/28)
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- Scope and limitations of the Minisci reaction for the synthesis of aza-heterocycles
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Attempts to prepare several classes of aza-heterocycles by application of the Minisci radical cyclisation reaction are described. Competing β-scission, hydrolytic cleavage and lactonisation reactions were found to be major hurdles to adopting this strategy for the synthesis of such targets.
- Burgin, Ryan N.,Jones, Simon,Tarbit
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scheme or table
p. 6772 - 6774
(2010/04/27)
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- Composition of the cloacal gland secretion of tuatara, Sphenodon punctatus
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The lipophilic content of the cloacal gland secretion of the tuatara (Sphenodon punctatus) was investigated. GC/EI-MS Analysis of CH2Cl2 extracts of the secretions revealed triacylglycerols as major glandular constituents. Twelve major medium-chain fatty acids were found to be conjugated to glycerol in different combinations, resulting in complex mixtures. These acids were identified by transesterification and subsequent derivatization of natural samples, and their structures were verified by synthesis. The natural glycerides contain predominantly three of the following acids: octanoic (A), (E)- and (Z)-oct-4-enoic (B and C, resp.), (4E,6Z)-octa-4,6-dienoic (tuataric acid;D), (R)-2,6-dimethylheptanoic (E), (R)-2,6-dimethylhept-5-enoic (F), (Z)-dec-4-enoic (G), (4Z,7Z)-deca-4,7-dienoic (H), (R)-3,7-dimethyloct-6-enoic (I), (R)-4,8-dimethylnon-7-enoic (J), (2R,6S)-2,6,10-trimethylundec-9-enoic (K), and (2R,5E)-2,6,10-trimethylundeca-5,9-dienoic acids (L). Several additional acids, occurring in trace amounts only, were tentatively identified by MS. The elucidation of the absolute configuration of the acids was performed by GC on chiral phases. Individual tuatara show specific mixtures of glycerides with up to 100 components. The individual mixtures may permit individual recognition because the bouquets seem to be stable over years.
- Flachsbarth, Birte,Fritzsche, Matthias,Weldon, Paul J.,Schulz, Stefan
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scheme or table
p. 1 - 37
(2010/04/23)
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- Studies on the mechanism, selectivity, and synthetic utility of lactone reduction using SmI2 and H2O
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Although simple aliphatic esters and lactones have long been thought to lie outside the reducing range of SmI2, activation of the lanthanide reagent by H2O allows some of these substrates to be manipulated in an unprecedented fashion. For example, the SmI2-H2O reducing system shows complete selectivity for the reduction of 6-membered lactones over other classes of lactones and esters. The kinetics of reduction has been studied using stopped-flow spectrophotometry. Experimental and computational studies suggest that the origin of the selectivity lies in the initial electron-transfer to the lactone carbonyl. The radical intermediates formed during lactone reduction with SmI2-H2O can be exploited in cyclizations to give cyclic ketone (or ketal) products with high diastereoselectivity. The cyclizations constitute the first examples of ester-alkene radical cyclizations in which the ester carbonyl acts as an acyl radical equivalent.
- Parmar, Dixit,Duffy, Lorna A.,Sadasivam, Dhandapani V.,Matsubara, Hiroshi,Bradley, Paul A.,Flowers II, Robert A.,Procter, David J.
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supporting information; experimental part
p. 15467 - 15473
(2010/02/16)
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- A chemical switch for the modulation of the functional activity of higher homologues of histamine on the human histamine H3 receptor: Effect of various substitutions at the primary amino function
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In an effort to establish the structural requirements for agonism, neutral antagonism, and inverse agonism at the human histamine H3 receptor (H3R) we have prepared a series of higher homologues of histamine in which the terminal nitrogen of the side chain has been either mono- or disubstituted with several aliphatic, alicyclic, and aromatic moieties or incorporated in cyclic systems. The novel ligands have been pharmacologically investigated in vitro for their affinities on the human H3R and H4R subtypes by radioligand displacement experiments and for their intrinsic H3R activities via a CRE-mediated β-galactosidase reporter gene assay. Subtle changes of the substitution pattern at the side chain nitrogen alter enormously the pharmacological activity of the ligands, resulting in a series of compounds with a wide spectrum of pharmacological activities. Among the several neutral H3R antagonists identified within this series, compounds 2b and 2h display an H3R affinity in the low nanomolar concentration range (pKi values of 8.1 and 8.4, respectively). A very potent and selective H3R agonist (11, pEC 50 = 8.9, α = 0.94) and a very potent, though not highly selective, H3R inverse agonist (2k, pIC50 = 8.9, α = -0.97) have been identified as well.
- Govoni, Marinella,Lim, Herman D.,El-Atmioui, Dris,Menge, Wiro M. P. B.,Timmerman, Henk,Bakker, Remko A.,Leurs, Rob,De Esch, Iwan J. P.
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p. 2549 - 2557
(2007/10/03)
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- Synthesis of docosahexaenoic acid derivatives designed as novel PPARγ agonists and antidiabetic agents
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To discover novel peroxisome proliferator-activated receptor γ (PPARγ) agonists that could be used as antidiabetic agents, we designed docosahexaenoic acid (DHA) derivatives (2 and 3), which have a hydrophilic substituent at the C(4)-position, based on the crystal structure of the ligand-binding pocket of PPARγ. These compounds were synthesized via iodolactone as a key intermediate. We found that both DHA derivatives (2 and 3) showed PPARγ transactivation higher than, or comparable to, that of pioglitazone, which is a TZD derivative used as an antidiabetic agent. DHA derivatives related to these potent compounds 2 and 3 were also synthesized to study structure-activity relationships. Furthermore, 4-OH DHA 2, which shows strong PPARγ transcriptional activity, was separated as an optically pure form.
- Itoh, Toshimasa,Murota, Itsuki,Yoshikai, Kazuyoshi,Yamada, Sachiko,Yamamoto, Keiko
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- METHOD FOR PRODUCING 1,6 HEXANE DIOL
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The invention relates to a method for producing 1,6 hexane diol from a mixture of carboxylic acids containing hexanedioic acid, 6-hydroxy caproic acid and small quantities of 1,4 cyclohexane diol, said mixture being a by-product obtained during the oxidation of cyclohexane to cyclohexanone/cyclohexanol using oxygen or gases containing oxygen by the extraction of water from the reaction mixture, the method including the esterification of the acids and subsequent hydrogenation. According to said method, the alcohol is separated from the mixtures of alcohols and low-boilers obtained after esterification and/or hydrogenation by a membrane system and is returned to the esterification step.
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Page/Page column 13
(2008/06/13)
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- Polycyclic molecules from linear precursors: Stereoselective synthesis of clavolonine and related complex structures
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(Chemical Equation Presented) A clever way to clavolonine: The total synthesis of the lycopodium alkaloid clavolonine (2) from a linear precursor 1 that contains the complete 16-carbon-atom chain is reported (see scheme). Intramolecular and transannular c
- Evans, David A.,Scheerer, Jonathan R.
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p. 6038 - 6042
(2007/10/03)
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- Inhibitors of cholesteryl ester transfer protein
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This invention relates to inhibitors of CETP and methods for producing these inhibitors. The invention also provides pharmaceutical compositions comprising the inhibitors of the invention and methods of utilizing the inhibitors and pharmaceutical compositions in the treatment and prevention of various disorders mediated by CETP.
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Page/Page column 29
(2010/02/15)
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- METHOD FOR THE PRODUCTION OF 1,6-HEXANEDIOL
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The invention relates to a method for producing 1,6-hexanediol and, optionally, e-caprolactone. According to the inventive method, the carboxylic acid obtained by oxidizing cyclohexane is esterified, the esterified mixture is separated into an ester fraction and a bottom fraction, and the ester fraction is hydrated so as to obtain 1,6-hexanediol. The bottom fraction is hydrolyzed with water and is returned into the esterified mixture. Hydrolyzing the bottom fraction with water allows the method to be simplified while preventing metal oxides from being emitted and being deposited on parts of the installation, a phenomenon that occurs during reprocessing of the bottom fraction by means of reesterification.
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Page/Page column 10
(2008/06/13)
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- Synthesis haptens and development of an immunoassay for the olive fruit fly pheromone
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An enzyme-linked immunosorbent assay (ELISA) for the olive fruit fly pheromone, Bactrocera oleae Gmelin, was developed. The assay uses polyclonal antibodies, raised in rabbits, against (±)-β-[3-(1,7-dioxaspiro[5.5] undecane)]propionic acid, 2 (hapten I), conjugated to the KLH (keyhole limpet hemocyanin) by the carbodiimide method. A second hapten, (±)-δ-[3- (1,7-dioxaspiro[5.5]undecane)]-butylamine, 3 (hapten II), after conjugation to a biotin moiety, was used for indirect immobilization onto ELISA microwells precoated with the glycoprotein avidin. The developed ELISA method measures the synthetic olive fruit fly pheromone in concentrations ranging between 0.08 and 10 μg/mL and shows great promise for practical applications for pheromone detection in environmental and biological samples. The results obtained strongly indicate that this technique, to our knowledge the first insect pheromone enzyme-linked immunosorbent assay so far reported, is a fast, sensitive, inexpensive, and highly convenient method for the analysis of a volatile and low molecular weight compound such as 1,7-dioxaspiro[5.5]undecane, 1.
- Neokosmidi, Afroditi,Ragoussis, Valentine,Zikos, Christos,Paravatou-Petsotas, Maria,Livaniou, Evangelia,Ragoussis, Nikitas,Evangelatos, Gregory
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p. 4368 - 4374
(2007/10/03)
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- Synthesis of a tripeptide derivative containing the Gln-Arg hydroxyethylene dipeptide isostere
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(Chemical Equation Presented) The protected hydroxyethylene dipeptide isostere of Gln-Arg and the tripeptide derivative 1 were synthesized as components of potential peptidase inhibitors.
- Brewer, Matthias,James, Clint A.,Rich, Daniel H.
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p. 4779 - 4782
(2007/10/03)
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- METHOD FOR PRODUCING 1,6-HEXANEDIOL WITH A PURITY OF GREATER THAN 99.5 %
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The invention relates to a method for producing 1,6-hexanediol by hydrogenating adipic acid dialkyl ester, 6-hydroxycaproic acid alkyl ester, 1,4-cyclohexanedione and 4-hydroxycyclohexan-1-one as ester mixtures containing impurities. The inventive method is characterized in that the ester mixtures are treated with an acetalizing agent before hydrogenation. The invention also relates to a method for producing 1,6-hexanediol by hydrogenating adipic acid dialkyl ester, 6-hydroxycaproic acid alkyl ester, 1,4-cyclohexanedione and 4-hydroxycyclohexan-1-one as an ester mixture containing impurities. This method is characterized in that during the esterification of a dicarboxylic acid mixture with a low-molecular alcohol, said mixture containing adipic acid, 6-hydroxycaproic acid and small amounts of 1,4-cyclohexanediols and accruing as a byproduct produced during the oxidation of cyclohexane into cyclohexanone/cyclohexanol with oxygen or gases containing oxygen and by extracting water from the reaction mixture, an acetalizing agent is added that is different from said low-molecular alcohol.
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Page/Page column 9-10
(2008/06/13)
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- METHOD FOR PRODUCING HEXANEDIOL
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A process for preparing 1,6-hexanediol from a carboxylic acid mixture comprising adipic acid, 6-hydroxycaproic acid and small amounts of 1,4-cyclohexanediols which is obtained as by-product in the oxidation of cyclohexane to cyclohexanone/cyclohexanol after water extraction of the reaction mixture followed by extraction with aqueous sodium hydroxide solution, by esterification of the acids and hydrogenation comprisesa) liberating the carboxylic acids from the alkaline extract by addition of a mineral acid,b) fractionating the organic phase comprising carboxylic acids to give a distillate comprising the low molecular weight monocarboxylic acids and a residue comprising adipic acid and 6-hydroxycaproic acid,c) reacting the monocarboxylic an dicarboxylic acids present in the aqueous dicarboxylic acid mixture with a low molecular weight alcohol to give the corresponding carboxylic esters,d) freeing the esterification mixture obtained of excess alcohol and low boilers in a first distillation step,e) fractionating the bottom product in a second distillation step to give an ester fraction essentially free of 1,4-cyclohexanediols and a fraction comprising at least the major part of the 1,4-cyclohexanediols,f) catalytically hydrogenating the ester fraction which is essentially free of 1,4-cyclohexanediols andg) isolating 1,6-hexanediol from the hydrogenation product in a manner known per se in a final distillation step.
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- Efficient synthesis of an enantiopure β-lactam as an advanced precursor of thrombin and tryptase inhibitors
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A new and efficient synthesis of a β-lactam that is an advanced precursor of inhibitors of thrombin and tryptase is reported. The reaction sequence is based on the use of an inexpensive enantiomerically pure starting material and is designed to allow acce
- Annunziata, Rita,Benaglia, Maurizio,Cinquini, Mauro,Cozzi, Franco,Maggioni, Francesco,Puglisi, Alessandra
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p. 2952 - 2955
(2007/10/03)
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- Conversion of (Z)-1,4-dihydroxyalk-2-enes into 2,5-dihydrofurans and of alkane-1,4-diols into tetrahydrofurans via acid-catalysed cyclisation of the monoisoureas formed by their copper(I)-mediated reactions with dicyclohexylcarbodiimide
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(Z)-1,4-dihydroxyalk-2-enes were converted into 2,5-dihydrofurans and alkane-1,4-diols were converted into tetrahydrofurans via acid-catalysed cyclisation of the monoisoureas. The reaction involved protonation of the carbodiimide by acidic phenol followed by reaction with alkanol. Pd/CaCo3-quinoline catalyst system was employed in the presence of a little triethylamine to overcome partial hydrogenolysis.
- Duffy, Michael G.,Grayson, David H.
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p. 1555 - 1563
(2007/10/03)
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- Efficient synthesis of B- and C-rings components of phycobilin derivatives for structure/function analysis of phytochrome
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B- and C-Rings components of phycobilin derivatives were efficiently prepared starting from the corresponding lactones. This synthetic method made it possible to prepare not only phycocyanobilin (PCB), but also PCB derivatives having butanoic acid side chain(s) instead of propanoic one(s), regioselectively monoesterified PCB derivatives at C8 or C12, and regioisomers of PCB with respect to methyl and propanoic acid substituents of B- and C-rings for the first time toward the structure/function analysis of phytochrome.
- Ohta, Atsuko,Sawamoto, Daisuke,Jayasundera, Krishanthi Padmarani,Kinoshita, Hideki,Inomata, Katsuhiko
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p. 492 - 493
(2007/10/03)
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- Convenient one pot conversion of acetals into alcohols
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Various acetals are conveniently converted into alcohols using a one pot procedure that combines hydrolysis of an acetal by triflouromethanesulfonic acid in tetrahydrofuran and tert-butylamine borane reduction of the resulting aldehyde.
- Lukin, Kirill A.,Yang, ChengXi,Bellettini, John R.,Narayanan,Leanna, M. Robert,Rasmussen, Michael
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