- A BULKY LIGAND AND ITS ORGANOMETALLIC COMPOUND: SYNTHESIS OF HEPTAMETHYLINDENE AND A FERROCENE-TYPE COMPLEX, Fe(η5-C9Me7)2
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A bulky new indene, 1-H-1,2,3,4,5,6,7-heptamethylindene, has been synthesized and its application to organometallic chemistry is suggested.
- Miyamoto, T. Ken,Tsutsui, Minoru,Chen, Li-Ban
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- An expeditious synthesis of (±)-desepoxy-4,5-didehydromethylenomycin A methyl ester
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A total synthesis of the racemic methyl ester of desepoxy-4,5-didehydromethylenomycin A has been achieved in six steps with an overall yield of 31% starting from diethyl methanephosphonate. The key steps include the Nazarov cyclization of the dienone 7 leading to the α-phosphoryl cyclopentenone 8 and the Horner-Wittig reaction of the latter employed for the introduction of the exocyclic methylene moiety.
- Balczewski, Piotr,Mikolajczyk, Marian
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- Chemo- and Regioselective Functionalization of Nortrilobolide: Application for Semisynthesis of the Natural Product 2-Acetoxytrilobolide
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The difference in reactivity of the hexaoxygenated natural product thapsigargin (1) and the pentaoxygenated nortrilobolide (3) was compared in order to develop a chemo- and regioselective method for the conversion of nortrilobolide (3) into the natural product 2-acetoxytrilobolide (4). For the first time, a stereoselective synthesis of 2-acetoxytrilobolide (4) is described, which involves two key reactions: the first chemical step was a one-pot substitution-oxidation reaction of an allylic ester into its corresponding α,β-unsaturated ketone. The second process consisted of a stereoselective α′-acyloxylation of the key intermediate α,β-unsaturated ketone to afford its corresponding acetoxyketone, which was converted into 2-acetoxytrilobolide (4) in a few steps. This innovative approach would allow the synthesis of a broad library of novel and valuable penta- and hexaoxygenated guaianolides as potential anticancer agents.
- Doan, Nhu Thi Quynh,Crestey, Fran?ois,Olsen, Carl Erik,Christensen, S?ren Br?gger
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- Chemistry of renieramycins. Part 13: Isolation and structure of stabilized renieramycin type derivatives, renieramycins W-Y, from Philippine blue sponge Xestospongia sp., pretreated with potassium cyanide
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Three new bistetrahydroisoquinoline marine natural products, renieramycins W (1w), X (1x), and Y (1y), along with two known renieramycins M (1m) and T (1t), were isolated from the pretreated Philippine blue sponge Xestospongia sp. with KCN and their structures were elucidated by comparing their spectral data with those of 1m, 1t, and N-acetylsafracin B (11). Renieramycins W (1w) and X (1x) are the first examples of tiglic acid ester derivatives at the C-1 side chain. Renieramycin Y (1y) possesses a characteristic substitution pattern in A-ring and isolation of it from marine organism strongly evidences to link the possible precursor 3-hydroxy-5-methyl-O-methyltyrosine with both renieramycin and ecteinascidin marine natural products.
- Tatsukawa, Mari,Punzalan, Louvy Lynn C.,Magpantay, Hilbert D.S.,Villase?or, Irene M.,Concepcion, Gisela P.,Suwanborirux, Khanit,Yokoya, Masashi,Saito, Naoki
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- Synthesis, characterisation, and polymerisation studies of hexamethylindenyl zirconocenes and hafnocenes
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Abstract A family of group 4 metallocene complexes based on the hexamethylindenyl ligand (C9Me6H; Ind#) have been prepared and fully characterised. The complexes rac-Ind#2ZrCl2 (rac-1), meso-Ind#2ZrCl2 (meso-1), rac-Ind#2HfCl2 (rac-2), meso-Ind#2HfCl2 (meso-2) were prepared by the reaction of Ind#Li with the corresponding MCl4 (where M = Zr, Hf); and rac-Ind#2Zr(CH2Ph)2 (rac-3) was derived from rac-1 using two equivalents of potassium benzyl (KCH2Ph). All five species were characterised by NMR spectroscopy, single crystal X-ray diffraction and studied using density functional theory. The zirconocenes were tested for their activity as solution-phase ethylene polymerisation catalysts and rac-1 was found to outperform the meso-1 at most temperatures. The benzyl analogue, rac-3, peaked at more than double the activity reported for the dihalide species.
- Arnold, Thomas A.Q.,Buffet, Jean-Charles,Turner, Zo? R.,O'Hare, Dermot
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- Stereoselective Total Synthesis of (-)-Renieramycin T
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A stereoselective total synthesis of (-)-Renieramycin T (1t) from a key tetrahydroisoquinoline intermediate previously utilized in our formal total synthesis of Ecteinascidin 743 is described. The synthesis features a concise approach for construction of the pentacyclic framework using a Pictet-Spengler cyclization of bromo-substituted carbinolamine 17, which obviates the regioselectivity problem of the Pictet-Spengler cyclization. The results of cytotoxicity studies are also presented.
- Yokoya, Masashi,Toyoshima, Ryoko,Suzuki, Toshihiro,Le, Vy H.,Williams, Robert M.,Saito, Naoki
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- Chemistry of renieramycins. Part 14: Total synthesis of renieramycin i and practical synthesis of cribrostatin 4 (renieramycin H)
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The first total synthesis of (±)-renieramycin I, which was isolated from the Indian bright blue sponge Haliclona cribricutis, is described. The key step is the selenium oxide oxidation of pentacyclic bis-p-quinone derivative (3) stereo- and regioselectively. We also report a large-scale synthesis of cribrostatin 4 (renieramycin H) via the C3-C4 double bond formation in an early stage based on the Avenda?o's protocol, from readily available 1-acetyl-3-(3-methyl-2,4,5-trimethylphenyl)methyl-piperazine-2,5-dione (8) in 18 steps (8.3% overall yield). The synthesis provides unambiguous evidence supporting the original structure of renieramycin I.
- Yokoya, Masashi,Kobayashi, Keiichiro,Sato, Mitsuhiro,Saito, Naoki
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- Chemistry of renieramycins. Part 11: Total synthesis of (±)-cribrostatin 4
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A 19-step synthesis of (±)-cribrostatin 4 (1) from readily available piperazine-2,5-dione derivative 6 is described. The synthesis features the concise construction of a pentacyclic framework, followed by the base-catalyzed epimerization of the C-1 stereo center of aldehyde (11). The results of cytotoxicity studies are also presented.
- Yokoya, Masashi,Ito, Hiroshi,Saito, Naoki
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- RhIII-Catalyzed C-H (Het)arylation/Vinylation of N-2,6-Difluoroaryl Acrylamides
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RhIII-catalyzed sp2 C-H cross-coupling of acrylamides with organoboron reactants has been accomplished using a commercially available N-2,6-difluoroaryl acrylamide auxiliary. A broad range of aryl and vinyl boronates as well as a variety of heterocyclic boronates with strong coordinating ability can serve as the coupling partners. This transformation proceeds under moderate reaction conditions with excellent functional group tolerance and high regioselectivity.
- Wang, Huai-Wei,Qiao, Yu-Han,Wu, Jia-Xue,Wang, Qiu-Ping,Tian, Meng-Xin,Li, Yong-Fei,Yao, Qing-Xia,Li, Da-Cheng,Dou, Jian-Min,Lu, Yi
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supporting information
p. 656 - 662
(2021/02/01)
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- Synthetic Studies on Selective, Proapoptotic Isomalabaricane Triterpenoids Aided by Computational Techniques
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The isomalabaricanes comprise a large family of marine triterpenoids with fascinating structures that have been shown to be selective and potent apoptosis inducers in certain cancer cell lines. In this article, we describe the successful total syntheses of the isomalabaricanes stelletin A, stelletin E, and rhabdastrellic acid A, as well as the development of a general strategy to access other natural products within this unique family. High-throughput experimentation and computational chemistry methods were used in this endeavor. A preliminary structure-activity relationship study of stelletin A revealed the trans-syn-trans core motif of the isomalabaricanes to be critical for their cytotoxic activity.
- Boyko, Yaroslav D.,Huck, Christopher J.,Ning, Shang,Shved, Alexander S.,Yang, Cheng,Chu, Tiffany,Tonogai, Emily J.,Hergenrother, Paul J.,Sarlah, David
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supporting information
p. 2138 - 2155
(2021/02/09)
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- Erratum: Synthetic Studies on Selective, Proapoptotic Isomalabaricane Triterpenoids Aided by Computational Techniques (J. Am. Chem. Soc. (2021) 143:4 (2138-2155) DOI: 10.1021/jacs.0c12569)
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Figure 2c and the accompanying text on page 2140, as well as the SI, mistakenly stated the use of AD-mix-a. AD-mix- ? was used for the transformation from 11 to (+)-13. All structures drawn are correct, and all conclusions remain the same. A revised Supporting Information document that reflects this correction is also available.
- Boyko, Yaroslav D.,Chu, Tiffany,Hergenrother, Paul J.,Huck, Christopher J.,Ning, Shang,Sarlah, David,Shved, Alexander S.,Tonogai, Emily J.,Yang, Cheng
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supporting information
p. 12418 - 12418
(2021/08/30)
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- Bromo Radical-Mediated Photoredox Aldehyde Decarbonylation towards Transition-Metal-Free Hydroalkylation of Acrylamides at Room Temperature
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Herein, we report a visible-light-mediated hydroalkylation reaction of alkenes using easily available aldehydes as alkyl sources via bromo radical-promoted photoredox decarbonylation. This protocol provides an alternative entry to C(sp3)?C(sp3) bond formation and features considerable advantages including mild and clean reaction conditions, obviation for transition-metal catalyst, and good functional group compatibility.
- Deng, Guo-Jun,Huang, Huawen,Sun, Zhaozhao,Wang, Qiaolin
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supporting information
(2021/12/03)
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- Stereospecific Electrophilic Fluorocyclization of α,β-Unsaturated Amides with Selectfluor
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An efficient fluorocyclization of α,β-unsaturated amides through a formal halocyclization process is developed. The reaction proceeds under transition-metal-free conditions and leads to the formation of fluorinated oxazolidine-2,4-diones with excellent regio- and diastereoselectivity. The evaluation of the reaction mechanism based on preliminary experiments and density functional theory calculations suggests that a synergetic syn-oxo-fluorination occurs and is followed by an anti-oxo substitution reaction. The reaction opens a new window in the field of stereospecific fluorofunctionalization.
- Fei, Haiyang,Fu, Yao,Jalani, Hitesh B.,Li, Guigen,Lu, Hongjian,Wu, Hongmiao,Xu, Zheyuan,Zhu, Lin
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supporting information
(2020/03/30)
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- Formal Lossen Rearrangement/[3+2] Annulation Cascade Catalyzed by a Modified Cyclopentadienyl RhIII Complex
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It has been established that a cyclopentadienyl RhIII complex with two phenyl groups and a pendant amide moiety catalyzes the formal Lossen rearrangement/[3+2] annulation cascade of N-pivaloyl benzamides and acrylamides with alkynes leading to substituted indoles and pyrroles. Mechanistic studies revealed that this cascade reaction proceeds via not the Lossen rearrangement to form anilides or enamides but C?H bond cleavage, alkyne insertion, and the formal Lossen rearrangement.
- Yamada, Takayuki,Shibata, Yu,Kawauchi, Susumu,Yoshizaki, Soichi,Tanaka, Ken
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supporting information
p. 5723 - 5727
(2018/04/11)
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- Nickel-Catalyzed Intramolecular Arylcyanation for the Synthesis of 3,3-Disubstituted Oxindoles
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A nickel-catalyzed arylcyanation reaction for the synthesis of 3,3-disubstituted oxindoles has been developed. This method features a bench-stable precatalyst system and serves as an economical alternative to the existing palladium-catalyzed arylcyanations described to date. A wide scope of oxindole products were accessible in moderate to good yields, and the rich chemistry of the newly installed nitrile functional group was demonstrated in the synthesis of various oxindole derivatives.
- Yen, Andy,Lautens, Mark
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supporting information
p. 4323 - 4327
(2018/07/29)
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- A natural product scurfpea and its enantiomer asymmetric synthetic method
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The invention discloses a natural product fructus psoraleae phenol and an asymmetric synthesis method of an enantiomer thereof, belongs to the field of chemical synthesis, relates to a chemical synthesis technology, and particularly relates to a natural product Bakuchoil with optical activity and a preparation method of the enantiomer ent-Bakuchoil of the natural product. According to the method disclosed by the invention, tiglic acid and tert-butyl acetate which are easily available industrially are taken as initial raw materials to synthesize a key midbody compound 11, subsequently based of the key midbody, the natural product Bakuchoil with optical activity and the enantiomer ent-Bakuchoil thereof can be respectively synthesized by two short synthesis strategies. The method disclosed by the invention is simple to operate, convenient in separation operation, high in yield and good in selectivity, and the used reagents are all common reagents.
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Paragraph 0050-0052
(2017/10/22)
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- Iron-Catalyzed C?H Alkynylation through Triazole Assistance: Expedient Access to Bioactive Heterocycles
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Triazole assistance enabled the first iron-catalyzed C?H alkynylation of arenes, heteroarenes, and alkenes. The modular TAM directing group set the stage for a sequential C?H alkynylation/annulation strategy with ample scope, enabling the iron-catalyzed assembly of isoquinolones, pyridones, pyrrolones, and isoindolinones with high levels of chemo-, site-, and regioselectivity.
- Cera, Gianpiero,Haven, Tobias,Ackermann, Lutz
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supporting information
p. 3577 - 3582
(2017/03/20)
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- Copper-Promoted Thiolation of C(sp2)–H Bonds Using a 2-Amino Alkylbenzimidazole Directing Group
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A copper-promoted thiolation of C(sp2)–H bonds with disulfides was achieved by using 2-amino alkylbenzimidazole (MBIP amine) as a new and removable N,N-bidentate directing group. This strategy gives a variety of functionalized thioethers in moderate to excellent yields in a simple and efficient way. Importantly, the substrate scope is not limited to aromatic amides; diverse alkenyl amides are also compatible. Furthermore, this synthetic approach provides a potentially feasible way to achieve structural modification of related benzimidazole-containing compounds through direct C–H activation.
- Liu, Shuang-Liang,Li, Xue-Hong,Shi, Tan-Hao,Yang, Guang-Chao,Wang, Hai-Li,Gong, Jun-Fang,Song, Mao-Ping
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supporting information
p. 2280 - 2289
(2017/05/01)
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- Nickel-Catalyzed Sulfonylation of C(sp2)–H Bonds with Sodium Sulfinates
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The first nickel-catalyzed ortho-sulfonylation of C(sp2)–H bonds with sodium sulfinates directed by (pyridin-2-yl)isopropylamine (PIP-amine) is described. This strategy exhibits a broad substrate scope and good functional group tolerance with high monosulfonylation selectivity. Besides arenes and heteroarenes, the reaction can also be extended to alkenes, providing diverse diaryl and alkyl aryl sulfones in high yields. Furthermore, a plausible Ni(I)/Ni(III) mechanism is outlined based on our experimental results and related precedents. (Figure presented.).
- Liu, Shuang-Liang,Li, Xue-Hong,Zhang, Shu-Sheng,Hou, Sheng-Kai,Yang, Guang-Chao,Gong, Jun-Fang,Song, Mao-Ping
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supporting information
p. 2241 - 2246
(2017/07/07)
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- Intramolecular Nitrofuran Diels-Alder Reactions: Extremely Substituent-Tolerant Cycloadditions via Asynchronous Transition States
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Nitrofurans undergo intramolecular Diels-Alder reactions with tethered electron-poor dienophiles more rapidly and in higher yield than non-nitrated furans. Computational studies indicate that increased stabilization of a partial positive charge on the nitro-substituted carbon in both transition state and product is the driving force for these reactions. Frontier molecular orbital energy differences indicate a switch from normal to inverse electron demand upon nitration. There does not appear to be a contribution from any differences in aromatic stabilization energy between furans and nitrofurans. Calculations show that the nitrofuran reactions proceed via a highly asynchronous transition state allowing easier bond formation between two sterically hindered carbons.
- Cowie, Thomas Y.,Veguillas, Marcos,Rae, Robert L.,Rougé, Mathilde,Zurek, Justyna M.,Prentice, Andrew W.,Paterson, Martin J.,Bebbington, Magnus W. P.
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p. 6656 - 6670
(2017/07/15)
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- Tuning the Reactivity of Functionalized Diallylic Alcohols: Br?nsted versus Lewis Acid Catalysis
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The chemodivergent reactivity of bifunctional, enol thioether-containing diallylic alcohols in acidic medium is disclosed, highlighting the difference between strong Lewis acid and mild Br?nsted acid catalysis. In the presence of bismuth(III) triflate, allylic alcohol activation affords diversely substituted cyclopentenones in a Nazarov-type electrocyclization, whereas activation of the thioenol ether by p-toluenesulfonic acid provides an entry to α-sulfenylated β,γ-unsaturated ketones. Both methods represent a facile access to the corresponding products under mild conditions, using inexpensive and non-toxic catalytic systems.
- Lempenauer, Luisa,Du?ach, Elisabet,Lemière, Gilles
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supporting information
p. 10285 - 10288
(2017/08/07)
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- Catalytic Enantioselective Nazarov Cyclization
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A detailed account of an asymmetric Nazarov cyclization that leads to α-hydroxycyclopentenones bearing either vicinal, all-carbon quaternary centers, or vicinal quaternary and tertiary centers is given. The all-aliphatic examples represent the greatest challenge, as the dienone starting materials are not activated toward cyclization by an aryl group. The rational design and optimization of the substrates in parallel with optimization of the chiral Br?nsted acid catalyst is also described, as well as a series of diastereoselective transformations of a fully substituted cyclopentenone product.
- Jolit, Anais,Dickinson, Cody F.,Kitamura, Kei,Walleser, Patrick M.,Yap, Glenn P. A.,Tius, Marcus A.
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supporting information
p. 6067 - 6076
(2017/11/14)
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- Stereoselective Synthesis of 1-Tuberculosinyl Adenosine; A Virulence Factor of Mycobacterium tuberculosis
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Despite its status as one of the world's most prevalent and deadly bacterial pathogens, Mycobacterium tuberculosis (Mtb) infection is not routinely diagnosed by rapid and highly reliable tests. A program to discover Mtb-specific biomarkers recently identified two natural compounds, 1-tuberculosinyl adenosine (1-TbAd) and N6-tuberculosinyl adenosine (N6-TbAd). Based on their association with virulence, the lack of similar compounds in nature, the presence of multiple stereocenters, and the need for abundant products to develop diagnostic tests, synthesis of these compounds was considered to be of high value but challenging. Here, a multigram-scale stereoselective synthesis of 1-TbAd and N6-TbAd is described. As a key-step, a chiral auxiliary-mediated Diels-Alder cycloaddition was developed, introducing the three stereocenters with a high exo endo ratio (10:1) and excellent enantioselectivity (>98% ee). This constitutes the first entry into the stereoselective synthesis of diterpenes with the halimane skeleton. Computational studies explain the observed stereochemical outcome.
- Buter, Jeffrey,Heijnen, Dorus,Wan, Ieng Chim,Bickelhaupt, F. Matthias,Young, David C.,Otten, Edwin,Moody, D. Branch,Minnaard, Adriaan J.
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p. 6686 - 6696
(2016/08/16)
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- Δ3 Asymmetric synthesis method -2 - hydroxyl psoralen and analogue compound
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The invention belongs to the field of chemical synthesis, provides a novel method for synthesizing delta3-2-hydroxybakuchiol and particularly relates to an asymmetric synthesis method for delta3-2-hydroxybakuchiol and analog compounds. The delta3-2-hydroxybakuchiol and the analog compounds, the general formula of which is (I), are synthesized by an asymmetric synthesis route. Problems in the prior art, that the content of the delta3-2-hydroxybakuchiol obtained by extraction and separation from plants is very low, an extraction rate is very low, the delta3-2-hydroxybakuchiol is prone to oxidative deterioration in extraction and separation processes, and the like, are overcome by the method. The method can provide sufficient samples for related pharmaceutical research, and provides good foundations for pharmaceutical research on antibiosis, infection resistance, oxidation resistance, pigment deposition resistance, reduction of bone loss, immunosuppression, liver damage, sedation and hypnosis, and the like. In the formula (I), R1 is selected from 4-hydroxy, 3-hydroxy, 2-hydroxy, hydrogen, 4-methyl, 4-methoxy, 4-trifluoromethyl, 3,4-[d][1,3]dioxole, and 3,4-phenyl; R2 is selected from methyl, ethyl, and butyl; and R3 is selected from vinyl, ethyl and cyclopropyl.
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Paragraph 0026-0028
(2016/11/07)
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- Expedient Iron-Catalyzed C-H Allylation/Alkylation by Triazole Assistance with Ample Scope
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Triazole assistance set the stage for a unified strategy for the iron-catalyzed C-H allylation of arenes, heteroarenes, and alkenes with ample scope. The versatile catalyst also proved competent for site-selective methylation, benzylation, and alkylation with challenging primary and secondary halides. Triazole-assisted C-H activation proceeded chemo-, site-, and diastereo-selectively, and the modular TAM directing group was readily removed in a traceless fashion under exceedingly mild reaction conditions. One for all: A unified strategy for iron-catalyzed C-H allylation and alkylation was developed by the use of a triazole directing group that could be cleaved under exceedingly mild conditions.
- Cera, Gianpiero,Haven, Tobias,Ackermann, Lutz
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supporting information
p. 1484 - 1488
(2016/02/12)
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- Pd-Catalyzed α-Selective C-H Functionalization of Olefins: En Route to 4-Imino-β-Lactams
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Pd-catalyzed α-olefinic C-H activation of simple α,β-unsaturated olefins has been developed. 4-imino-β-lactam derivatives were readily synthesized via activation of α-olefinic C-H bonds with excellent cis stereoselectivity. A wide range of heterocycles at the β-position are compatible with this reaction. The product of 4-imino-β-lactam derivatives can be readily converted to 2-aminoquinoline which exists extensively in pharmaceutical drugs and natural products.
- Kong, Wei-Jun,Liu, Yue-Jin,Xu, Hui,Chen, Yan-Qiao,Dai, Hui-Xiong,Yu, Jin-Quan
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supporting information
p. 2146 - 2149
(2016/03/05)
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- Asymmetric dihydroxylation of esters and amides of methacrylic, tiglic, and angelic acid: No exception to the sharpless mnemonic!
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Literature findings on the facial selectivity of the Sharpless asymmetric dihydroxylation (SAD) of isobutyl angelate are contradictory and partly in conflict with the Sharpless mnemonic. We systematically screened the SAD of esters and amides of angelic, tiglic, and methacrylic acid. Enantiocontrol arose in 14 of the 15 reactions, culminating at 99 % ee for the Weinreb amide of tiglic acid. The absolute configurations of all the nonracemic products were established by (stereo)chemical correlations. Without exception, they conform to the Sharpless mnemonic.
- Weber, Fabian,Brückner, Reinhard
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supporting information
p. 2428 - 2449
(2015/04/22)
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- Enantioselective palladium(0)-catalyzed nazarov-type cyclization
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A Pd0-catalyzed asymmetric Nazarov-type cyclization is described. The optimized ligand for the reaction incorporates a weakly coordinating pyridine ring into a TADDOL-derived phosphoramidite (TADDOL=α,α,α,α-tetraaryl-1,3-dioxolane-4,5-dimethanol). The reaction leads to the formation of cyclopentenones as single diastereoisomers that incorporate two contiguous asymmetric centers, one tertiary and one an all-carbon-atom quaternary stereocenter, in high yield and optical purity. It is noteworthy that the reaction does not require that substrates should be activated by aryl substituents.
- Kitamura, Kei,Shimada, Naoyuki,Stewart, Craig,Atesin, Abdurrahman C.,Atein, Tülay A.,Tius, Marcus A.
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supporting information
p. 6288 - 6291
(2015/05/20)
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- An LC-MS/MS method to quantify acylcarnitine species including isomeric and odd-numbered forms in plasma and tissues
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Acylcarnitines are intermediates of fatty acid and amino acid oxidation found in tissues and body fluids. They are important diagnostic markers for inherited diseases of peroxisomal and mitochondrial oxidation processes and were recently described as biomarkers of complex diseases like the metabolic syndrome. Quantification of acylcarnitine species can become challenging because various species occur as isomers and/or have very low concentrations. Here we describe a new LC-MS/MS method for quantification of 56 acylcarnitine species with acyl-chain lengths from C2 to C18. Our method includes amino acid-derived positional isomers, like methacrylyl-carnitine (2-M-C3:1-CN) and crotonyl-carnitine (C4:1-CN), and odd-numbered carbon species, like pentadecanoyl-carnitine (C15:0-CN) and heptadecanoyl-carnitine (C17:0-CN), occurring at very low concentrations in plasma and tissues. Method validation in plasma and liver samples showed high sensitivity and excellent accuracy and precision. In an application to samples from streptozotocin-treated diabetic mice, we identified significantly increased concentrations of acylcarnitines derived from branched-chain amino acid degradation and of odd-numbered straight-chain species, recently proposed as potential biomarkers for the metabolic syndrome. In conclusion, the LC-MS/MS method presented here allows robust quantification of isomeric acylcarnitine species and extends the palette of acylcarnitines with diagnostic potential derived from fatty acid and amino acid metabolism.
- Giesbertz, Pieter,Ecker, Josef,Haag, Alexander,Spanier, Britta,Daniel, Hannelore
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p. 2029 - 2039
(2015/11/17)
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- Preparation of renieramycin left-half model compounds
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Model compounds of the left-half of renieramycins, which are anticancer marine natural products having an α-aminonitrile functionality, were prepared from phenylalanine derivatives. The key step of the transformation is the stereospecific construction of 1,3-cis stereochemistry via an exomethylene intermediate. The stereoselective α-aminonitrile formation under kinetically controlled conditions is also discussed. The initial cytotoxicity profiles are presented.
- Nakai, Keiyo,Kubo, Keiji,Yokoya, Masashi,Saito, Naoki
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p. 6529 - 6545
(2015/03/30)
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- Direct allylation of aromatic and α,β-unsaturated carboxamides under ruthenium catalysis
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The ruthenium-catalyzed oxidative allylation of aromatic and α,β-unsaturated carboxamides with allylic carbonates is described. These transformations proceed readily with complete linear γ-selectivity of substituted allylic carbonates. the Partner Organisations 2014.
- Kim, Mirim,Sharma, Satyasheel,Mishra, Neeraj Kumar,Han, Sangil,Park, Jihye,Kim, Minyoung,Shin, Youngmi,Kwak, Jong Hwan,Han, Sang Hoon,Kim, In Su
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supporting information
p. 11303 - 11306
(2014/11/07)
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- Ligand-promoted alkylation of C(sp3)-H and C(sp2)-H bonds
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9-Methylacridine was identified as a generally effective ligand to promote a Pd(II)-catalyzed C(sp3) - H and C(sp2) - H alkylation of simple amides with various alkyl iodides. This alkylation reaction was applied to the preparation of unnatural amino acids and geometrically controlled tri- and tetrasubstituted acrylic acids.
- Zhu, Ru-Yi,He, Jian,Wang, Xiao-Chen,Yu, Jin-Quan
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supporting information
p. 13194 - 13197
(2015/03/30)
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- Iron-catalyzed directed alkylation of aromatic and olefinic carboxamides with primary and secondary alkyl tosylates, mesylates, and halides
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Alkenes, arenes, and heteroarenes possessing an 8-quinolylamide group as the directing group are alkylated with primary and secondary alkyl tosylates, mesylate, and halides in the presence of Fe(acac) 3/ diphosphine as a catalyst and ArZnBr as a base. The reaction proceeds stereospeci fically for alkene substrates and takes place without loss of regiochemical integrity of the starting secondary tosylate, but with loss of the stereochemistry of the chiral center.
- Ilies, Laurean,Matsubara, Tatsuaki,Ichikawa, Saki,Asako, Sobi,Nakamura, Eiichi
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supporting information
p. 13126 - 13129
(2015/03/30)
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- Convenient synthesis of various substituted homotaurines from alk-2-enamides
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Various substituted homotaurines (=3-aminopropane-1-sulfonic acids) 6 were readily synthesized in satisfactory to good yields via the Michael addition of thioacetic acid to alk-2-enamides 3 (→4), followed by LiAlH4 reduction (→5) and performic acid oxidation (Scheme 1). The configuration of 'anti'-disubstituted homotaurine 'anti'-6h was deduced from the 3-(acetylthio)alkanamide (=S-(3-amino-1,2-dimethyl-3-oxopropyl) ethanethioate)'anti'-4h formed in the Michael addition, which was identified via the Karplus equation analysis, and confirmed by X-ray diffraction analysis. The current route is an efficient method to synthesize diverse substituted homotaurines, including 1-, 2-, and N-monosubstituted, as well as 1,2-, 1,N-, 2,N-, and N,N-disubstituted homotaurines (Table). Copyright
- Nai, Youfeng,Xu, Jiaxi
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p. 1355 - 1365
(2013/08/23)
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- Ir(III)-catalyzed mild C-H amidation of arenes and alkenes: An efficient usage of acyl azides as the nitrogen source
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Reported herein is the development of the Ir(III)-catalyzed direct C-H amidation of arenes and alkenes using acyl azides as the nitrogen source. This procedure utilizes an in situ generated cationic half-sandwich iridium complex as a catalyst. The reaction takes place under very mild conditions, and a broad range of sp2 C-H bonds of chelate group-containing arenes and olefins are smoothly amidated with acyl azides without the intervention of the Curtius rearrangement. Significantly, a wide range of reactants of aryl-, aliphatic-, and olefinic acyl azides were all efficiently amidated with high functional group tolerance. Using the developed approach, Z-enamides were readily accessed with a complete control of regio- and stereoselectivity. The developed direct amidation proceeds in the absence of external oxidants and releases molecular nitrogen as a single byproduct, thus offering an environmentally benign process with wide potential applications in organic synthesis and medicinal chemistry.
- Ryu, Jaeyune,Kwak, Jaesung,Shin, Kwangmin,Lee, Donggun,Chang, Sukbok
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supporting information
p. 12861 - 12868
(2013/09/23)
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- A facile asymmetric synthesis of Δ3-2-Hydroxybakuchiol, Bakuchiol and ent-Bakuchiol
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A facile asymmetric synthesis of Δ3-2-Hydroxybakuchiol, Bakuchiol, and ent-Bakuchiol is described through one common intermediate bearing a chiral all-carbon quaternary carbon center, which involves stereoselectively unconjugated alkylation of the α,β-unsaturated imide bearing Evans' auxiliary, Takai-Utimoto reaction, Negishi reaction, and Heck reaction as key steps.
- Xu, Qian-Qian,Zhao, Qun,Shan, Guang-Sheng,Yang, Xi-Cheng,Shi, Qi-Yuan,Lei, Xinsheng
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p. 10739 - 10746
(2013/12/04)
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- Chemistry of renieramycins. Part 12: An improved total synthesis of (±)-renieramycin G
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An improved total synthesis of (±)-renieramycin G (1g) from readily available 2-hydroxy-3-methyl-4,5-dimethoxybenzaldehyde (7) in 21 steps (6.3% overall yield) is described. The synthesis features the concise construction of a pentacyclic framework using the stereoselective Pictet-Spengler type cyclization reaction of lactam (25) with ethyl diethoxyacetate, followed by the base-catalyzed epimerization of the C-1 stereo center of aldehyde (30a). The results of cytotoxicity studies are also presented.
- Yokoya, Masashi,Shinada-Fujino, Kimiko,Yoshida, Saiko,Mimura, Masahiro,Takada, Hiroki,Saito, Naoki
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experimental part
p. 4166 - 4181
(2012/07/28)
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- Aerobic palladium(II)-catalyzed 5-endo-trig cyclization: An entry into the diastereoselective C-2 alkenylation of indoles with tri- and tetrasubstituted double bonds
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The endo trick: An endo ring closure onto the trigonal β carbon atom of α,β-unsaturated acceptors that are tethered to the indole nitrogen atom followed by amide cleavage enables the diastereoselective C-2 alkenylation of indoles with fully substituted double bonds. The carboxy group functions as a synthetically useful temporary tether (see scheme). Copyright
- Kandukuri, Sandeep R.,Schiffner, Julia A.,Oestreich, Martin
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supporting information; experimental part
p. 1265 - 1269
(2012/03/08)
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- Undirected arene and chelate-assisted olefin C-H bond activation: [Rh IIICp*]-catalyzed dehydrogenative alkene-arene coupling as a new pathway for the selective synthesis of highly substituted Z olefins
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Undirected/Directed Cross-Coupling: A new dehydrogenative Rh III-catalyzed cross-coupling reaction between bromoarenes bearing no directing group and vinylic substrates substituted by a chelating group is reported. An original reaction mechanism enables the use of internal alkenes in a Z-selective coupling. The application of 1,3-disubstituted or 1,2-homodisubstituted arenes leads to the formation of highly functionalized, complex, and valuable olefins as one single isomer. Copyright
- Wencel-Delord, Joanna,Nimphius, Corinna,Patureau, Frederic W.,Glorius, Frank
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supporting information; experimental part
p. 1208 - 1212
(2012/07/28)
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- RhIII-catalyzed oxidative olefination of vinylic C-H bonds: Efficient and selective access to Di-unsaturated α-amino acid derivatives and other linear 1,3-butadienes
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Olefin(s) get-together! A RhIII-catalyzed oxidative cross-coupling of different olefins was developed, resulting in the formation of valuable linear butadiene products and especially di-unsaturated α-amino acid derivatives. 1,1-Di-, 1,2-di-, and 1,1,2-trisubstituted olefins could be coupled with styrenes and acrylates. In these reactions, remarkably high levels of chemo-, regio-, and stereoselectivity were obtained, rendering this a valuable synthetic tool. Copyright
- Besset, Tatiana,Kuhl, Nadine,Patureau, Frederic W.,Glorius, Frank
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experimental part
p. 7167 - 7171
(2011/07/31)
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- BETA-AMINO ACIDS AND METHODS AND INTERMEDIATES FOR MAKING SAME
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Disclosed are β-amino acids that are unsubstituted in the β position; that are substituted in the β position with an aryl group; that are substituted in the α position with an aryl group; that bear two substituents in the α position; and/or that are substituted in the α and β positions with groups which, together with the carbon atoms at the α and β positions, form a ring. Also disclosed are methods for making the above-mentioned β-amino acids and other β-amino acids which involve providing an α,β-unsaturated imide; converting the α,β-unsaturated imide to a 2-substituted-isoxazolidin-5-one; and converting the 2-substituted-isoxazolidin-5-one to a β-amino acid.
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Page/Page column 13
(2011/10/02)
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- Antinociceptive effect of extracts and compounds from Hofmeisteria schaffneri
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Ethnopharmacological relevance: Hofmeisteria schaffneri (Asteraceae) is a medicinal plant widely commercialized in the most important Markets of Mexico City for the treatment of gastro-intestinal complaints and skin afflictions. Aim of the study: The main goals of this study were to establish the potential acute toxicity and the antinociceptive activity in animal models of several preparations and compounds from Hofmeisteria schaffneri. Materials and methods: The aqueous and organic extracts as well as the essential oil of Hofmeisteria schaffneri were prepared by infusion, maceration and hydrodistillation, respectively. Investigation of the acute toxicity was accomplished by the Lorke method. The antinociceptive effect was assessed using the writhing and the hot plate tests. Natural compounds were isolated by standard phytochemical procedures. In addition, a few thymol esters were prepared by chemical synthesis. The stability of natural and synthetic esters was qualitatively analyzed by measuring their susceptibility to hydrolysis by pig liver estearase and mouse plasma at 37°C. Results: The LD50 for each preparation tested was higher than 5000mg/kg revealing that they were not toxic to mice after exposure for short space of time. On the other hand, the extracts showed significant antinociceptive effect when tested in the hot plate model. The most active natural product as antinociceptive agent was hofmeisterin III (1) which also was the most stable in the stability study. Its pharmacological effect seems to be partially mediated by an opioid mechanism since naloxone inhibits its action. Using compound 1 as a lead molecule, several synthetic thymol esters were prepared and only compounds 13, 15 and 17 were antinoceptive at the dose of 1mg/kg. Conclusions: The present investigation provided evidence of the efficacy of several preparations of Hofmeisteria schaffneri as antinociceptive agents. The most active preparation was the essential oil which contained large amount of hofmeisterin III (1) and other thymol derivatives. Some novel synthetic analogs of hofmeisterin III with antinociceptive properties were discovered. The nature of the ester chain of these analogs did not have a clear impact on the antinociceptive activity. The phyto-preparations analyzed in this study were not toxic to mice according to the Lorke's test; therefore considering their long term use of the plant they might be secure for human consumption.
- Angeles-Lopez, Guadalupe,Perez-Vasquez, Araceli,Hernandez-Luis, Francisco,Deciga-Campos, Myrna,Bye, Robert,Linares, Edelmira,Mata, Rachel
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experimental part
p. 425 - 432
(2011/11/14)
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- New cyclopentadienyl, indenyl or fluorenyl substituted phosphine compounds and their use in catalytic reactions
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The invention is directed to a phosphine compound represented by general formula (1) wherein R' and R" independently are selected from alkyl, cycloalkyl and 2-furyl radicals, or R' and R" are joined together to form with the phosphorous atom a carbon-phosphorous monocycle comprising at least 3 carbon atoms or a carbon-phosphorous bicycle; the alkyl radicals, cycloalkyl radicals, and carbon-phosphorous monocycle being unsubstituted or substituted by at least one radical selected from the group of alkyl, cycloalkyl, aryl, alkoxy, and aryloxy radicals; Cps is a partially substituted or completely substituted cyclopentadien-1-yl group, including substitutions resulting in a fused ring system, and wherein a substitution at the 1-position of the cyclopentadien-1-yl group is mandatory when the cyclopentadien-1-yl group is not part of a fused ring system or is part of an indenyl group. Also claimed is the use of these phosphines as ligands in catalytic reactions and the preparation of these phosphines.
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Page/Page column 26
(2008/06/13)
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- Diastereoselective nickel-catalyzed reductive Aldol cyclizations using diethylzinc as the stoichiometric reductant: Scope and mechanistic insight
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In the presence of diethylzinc as a stoichiometric reductant, Ni(acac) 2 functions as an efficient precatalyst for the reductive aldol cyclization of α,β-unsaturated carbonyl compounds tethered to a ketone electrophile through an amide or an ester linkage. The reactions are tolerant of a wide range of substitution at both α,β-unsaturated carbonyl and ketone components and proceed smoothly to furnish β-hydroxylactams and β-hydroxylactones with generally high diastereoselectivities. A series of experiments, including deuterium-labeling studies, was carried out in an attempt to gain some insight into the possible reaction mechanisms that might be operative.
- Joensuu, Pekka M.,Murray, Gordon J.,Fordyce, Euan A. F.,Luebbers, Thomas,Hon, Wai Lam
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p. 7328 - 7338
(2008/12/22)
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- Asymmetric total synthesis of (-)-cribrostatin 4 (renieramycin H)
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(Chemical Equation Presented) Out of the blue: The convergent asymmetric total synthesis of the antitumor antibiotic (-)-cribrostatin 4 from the blue sponge Cribrochalina features asymmetric Staudinger and Pictet-Spengler reactions to form the tetrahydroisoquinoline moiety. These reactions were followed by a reductive opening/elimination of a tricyclic β-lactam and a Pictet-Spengler cyclization to access the unsaturated pentacyclic core.
- Vincent, Guillaume,Williams, Robert M.
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p. 1517 - 1520
(2008/04/05)
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- A catalytic asymmetric vinylogous mukaiyama aldol reaction
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A vinylogous Mukaiyama aldol reaction, conducted using 10 mol % of a BITIP catalyst and B(OMe)3 as an additive, effects an enantioselective four-carbon chain extension to give versatile Eαβ-unsaturated thiol esters.
- Heumann, Lars V.,Keck, Gary E.
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p. 4275 - 4278
(2008/02/13)
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- Enantioselective 1,3-dipolar cycloadditions of diazoacetates with electron-deficient olefins
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Equation presented A general strategy for highly enantioselective 1,3-dipolar cycloaddition of diazoesters to β-substituted, α-substituted, and α,β-disubstituted α,β-unsaturated pyrazolidinone imides is described. Cycloadditions utilizing less reactive α,β-disubstituted dipolarophiles require elevated reaction temperatures, but still provide the corresponding pyrazolines with excellent enantioselectivities. Finally, an efficient synthesis of (-)-manzacidin A employing this cycloaddition methodology as a key step is illustrated.
- Sibi, Mukund P.,Stanley, Levi M.,Soeta, Takahiro
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p. 1553 - 1556
(2008/02/04)
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- Elucidating the mechanism of the asymmetric aza-Michael reaction
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The mechanism of the palladium-catalysed asymmetric aza-Michael addition of aniline to α,β-unsaturated N-imide was examined from several aspects using a combination of techniques, including X-ray crystallography, mass spectrometry, NMR, UV/Vis spectroscopy, and kinetic studies. The binding of aniline to the dicationic palladium(II) metal centre was found to occur in two consecutive steps: The binding of the first aniline is fast and reversible, whereas the binding of the second aniline is slower and irreversible. This occurs in competition with the binding of the N-imide, which forms a planar six-membered chelate ring with the metal centre; coordinating through the 1,3-dicarbonyl moiety. Isotopic labelling revealed that the addition of N-H occurs in a highly stereoselective manner, allowing the synthesis of optically active β2- and β2.3-amino acid derivatives. The stereochemistry of the addition is postulated to be syn. In situ kinetic studies provided evidence for product inhibition. The binding of the N-imide to the catalyst was found to be the rate-limiting step. Aniline was found to be an inhibitor of the pre-catalyst. The study culminated in the design of a new reaction protocol. By maintaining a low concentration of the aniline substrate during the course of the reaction, significant enhancement of yield and enantioselectivity can be achieved.
- Phua, Pim Huat,Mathew, Suju P.,White, Andrew J. P.,De Vries, Johannes G.,Blackmond, Donna G.,Hii, King Kuok
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p. 4602 - 4613
(2008/02/09)
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- Asymmetric hydrogenation routes to deoxypolyketide chirons
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Asymmetric hydrogenations of monoenes and dienes were performed to obtain terminal deoxypolyketide fragments A and the corresponding internal Chirons B and C. The chiral N-heterocyclic carbene catalyst 1 was used throughout. Modest selectivities for hydrogenations of simple monoenes relayed into high selectivities for preparations of the terminal deoxypolyketide fragments in which either two hydrogenations or one and an optically pure starting material were used. Curiously, the face selectivities for hydrogenation of α,β-unsaturated esters were consistently opposite to those that had been observed for styrene and stilbene derivatives in previous work, and to closely related allylic alcohol and ether derivatives in this work. Plausible mechanisms for this differing behavior were deduced by using DFT calculations. It appears that the origin of the unusual stereoselectivity for the ester derivatives is transient metal-coordination of the ester carbonyl whereas there is no evidence that the allylic alcohol or ethers coordinate. The routes developed to α,ω-functionalized internal deoxypolyketide fragments are extremely practical. These begin with the Roche ester being converted into alkene and, in one case, diene derivatives. Catalyst control prevails in the hydrogenations of these substrates, but there is a significant "substrate vector" (a term we used to describe the influence of the substrate on a catalyst-controlled reaction). This is determined by minimization of 1,3-allylic strain and, in some cases, syn pentane interactions. This substrate vector can be constructively paired with the (dominant) catalyst vector by use of the appropriate enantiomer of 1. In the hydrogenation of a diene derivative, two chiral centers could be formed simultaneously with overall 11:1.0 selectivity; this is the first time this has been achieved in any asymmetric synthesis of a deoxypolyketide fragment. Throughout, diastereo-selectivities of the crude material in the syntheses of α,ω-functionalized internal deoxypolyketide fragments were in excess of 11:1.0 and chromatographically purified samples could be isolated in high yields with dr (dr = diastereomeric ratio) values consistently in excess of 40:1.0.
- Zhou, Jianguang,Ogle, James W.,Fan, Yubo,Banphavichit, Yorawit,Zhu, Ye,Burgess, Kevin
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p. 7162 - 7170
(2008/03/12)
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- Aromatic borylation/amidation/oxidation: A rapid route to 5-substituted 3-amidophenols
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5-Substituted 3-amidophenols are prepared by subjecting 3-substituted halobenzenes to an Ir-catalyzed aromatic borylation, followed by a Pd-catalyzed amidation, and finally an oxidation of the boronic ester intermediate. The entire C-H activation borylation/amidation/oxidation sequence can be accomplished without isolation of any intermediate arenes. Usefully, amide partners can include lactams, carbamates, and ureas.
- Shi, Feng,Smith III, Milton R.,Maleczka Jr., Robert E.
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p. 1411 - 1414
(2007/10/03)
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- Enantioselective 1,3-dipolar cycloaddition of nitrile imines to α-substituted and α,β-disubstituted α,β-unsaturated carbonyl substrates: A method for synthesizing dihydropyrazoles bearing a chiral quaternary center
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Dihydropyrazoles bearing a chiral quaternary center at the 5-position have been prepared by enantioselective 1,3-dipolar cycloaddition of nitrile imines to α-substituted- and α,β-disubstituted-α,β- unsaturated carbonyl substrates. Use of α,β-unsaturated carbonyl substrates with a l-benzyl-5,5-dimethylpyrazolidin-3-one auxiliary in conjunction with MgI2 and a bisoxazoline ligand derived from (1R,2S)-(+)-cis-1-amino-2-indanol 6 proved optimal to obtain chiral dihydropyrazoles with high enantio-selectivity (up to 99% ee).
- Sibi, Mukund P.,Stanley, Levi M.,Soeta, Takahiro
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p. 2371 - 2375
(2007/10/03)
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