- Synthesis, radiolabeling, and preliminary in vivo evaluation of [68ga] ipcat-nota as an imaging agent for dopamine transporter
-
Introduction: Novel radiotracer development for imaging dopamine transporters is a subject of interest because although [99mTc]TRODAT-1, [123I]β-CIT, and [123I]FP-CIT are commercially available;99Mo/99mTc generator is in short supply and123I production is highly dependent on compact cyclotron. Therefore, we designed a novel positron emission tomography (PET) tracer based on a tropane derivative through C-2 modification to conjugate NOTA for chelating68Ga, a radioisotope derived from a68Ge/68Ga generator. Methods: IPCAT-NOTA 22 was synthesized and labeled with [68Ga]GaCl4 ? at room tem-perature. Biological studies on serum stability, LogP, and in vitro autoradiography (binding assay and competitive assay) were performed. Furthermore, ex vivo autoradiography, biodis-tribution, and dynamic PET imaging studies were performed in Sprague Dawley rats. Results: [68Ga]IPCAT-NOTA 24 obtained had a radiochemical yield of ≥90% and a specific activity of 4.25 MBq/nmol. [68Ga]IPCAT-NOTA 24 of 85% radiochemical purity (RCP%) was stable at 37°C for up to 60 minutes in serum with a lipophilicity of 0.88. The specific binding ratio (SBR%) reached 15.8 ± 6.7 at 60 minutes, and the 85% specific uptake could be blocked through co-injection at 100-and 1000-fold of the cold precursor in in vitro binding studies. Tissue regional distribution studies in rats with [68Ga]IPCAT-NOTA 24 showed striatal uptake (0.02% at 5 minutes and 0.007% at 60 minutes) with SBR% of 6%, 25%, and 62% at 5–15, 30–40, and 60–70 minutes, respectively, in NanoPET studies. The RCP% of [68Ga]IPCAT-NOTA 24 at 30 minutes in vivo remained 67.65%. Conclusion: Data described here provide new information on the design of PET probe of conjugate/pendent approach for DAT imaging. Another chelator or another direct method of intracranial injection must be used to prove the relation between [68Ga]IPCAT-NOTA 24 uptake and transporter localization.
- Farn, Shiou-Shiow,Chang, Kang-Wei,Lin, Wan-Chi,Yu, Hung-Man,Lin, Kun-Liang,Tseng, Yu-Chin,Chang, Yu,Yu, Chung-Shan,Lin, Wuu-Jyh
-
p. 2577 - 2591
(2021/07/06)
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- Unified Approach to Furan Natural Products via Phosphine-Palladium Catalysis
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Polyalkyl furans are widespread in nature, often performing important biological roles. Despite a plethora of methods for the synthesis of tetrasubstituted furans, the construction of tetraalkyl furans remains non-trivial. The prevalence of alkyl groups in bioactive furan natural products, combined with the desirable bioactivities of tetraalkyl furans, calls for a general synthetic protocol for polyalkyl furans. This paper describes a Michael–Heck approach, using sequential phosphine-palladium catalysis, for the preparation of various polyalkyl furans from readily available precursors. The versatility of this method is illustrated by the total syntheses of nine distinct polyalkylated furan natural products belonging to different classes, namely the furanoterpenes rosefuran, sesquirosefuran, and mikanifuran; the marine natural products plakorsins A, B, and D and plakorsin D methyl ester; and the furan fatty acids 3D5 and hydromumiamicin.
- Chen, Violet Yijang,Kwon, Ohyun
-
supporting information
p. 8874 - 8881
(2021/03/17)
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- Palladium-catalysed regio- And stereoselective arylative substitution of γ,δ-epoxy-α,β-unsaturated esters and amides by sodium tetraaryl borates
-
Palladium-catalysed reactions of γ,δ-epoxy-α,β-unsaturated esters and amides with NaBAr4 reagents proceeded regio- and stereoselectively, producing allylic homoallyl alcohols with aryl-substituents in the allylic position for a wide range of substrates. A
- Artok, Levent,Bilgi, Yasemin,Ku?, Melih
-
supporting information
p. 6378 - 6383
(2020/09/07)
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- Intramolecular Diels-Alder Approaches to the Decalin Core of Verongidolide: The Origin of the exo-Selectivity, a DFT Analysis
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Verongidolide is a natural macrolactone recently isolated from a New Caledonia sponge, Verongidolae. The structure of this natural product is similar to the structure of superstolides, also isolated from a New Caledonian sponge, Neosiphonia superstes. From a biological point of view, verongidolide and superstolides A and B present potent cytotoxicity against human oral carcinoma KB (0.3 nM). By comparing the 1H NMR chemical shifts as well as the coupling constants, we conclude that verongidolide possesses a cis-decalin core and we hypothesize that the relative configuration of the cis-decalin core is similar to the one of superstolide A. To verify this hypothesis, intramolecular and transannular Diels-Alder reactions were attempted to construct the decalin core. Unexpectedly, the selectivity of the Diels-Alder reactions was exo and an in-depth DFT calculation of the key reaction mechanism was achieved in order to understand the factors controlling this unexpected selectivity.
- Maiga-Wandiam, Baba,Corbu, Andrei,Massiot, Georges,Sautel, Fran?ois,Yu, Peiyuan,Lin, Bernice Wan-Yi,Houk, Kendall N.,Cossy, Janine
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p. 5975 - 5985
(2018/05/14)
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- SYNTHESIS OF DISORAZOLES AND ANALOGS THEREOF AS POTENT ANTICANCER AGENTS
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In one aspect, the present disclosure provides disorazole analogs of the formula: Formula (I) wherein the variables are as defined herein. In another aspect, the present disclosure also provides methods of preparing the compounds disclosed herein. In another aspect, the present disclosure also provides pharmaceutical compositions and methods of use of the compounds disclosed herein. Additionally, drug conjugates with cell targeting moieties of the compounds are also provided.
- -
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Page/Page column 89; 94; 95
(2019/01/11)
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- Flow synthesis of (3R)- and (3S)-(E)-1-iodohexa-1,5-dien-3-ol: Chiral building blocks for natural product synthesis
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A concise procedure to prepare optically active (3R)- and (3S)-(E)-1-iodohexa-1,5-dien-3-ol was developed. Ethyl (E)-3-iodoacrylate was converted to racemic (E)-1-iodohexa-1,5-dien-3-ol under flow and batch conditions via successive half reduction followed by Grignard reaction. Kinetic resolution of the racemic alcohol was achieved under flow conditions by using lipase packed in a column to afford (3S)-(E)-1-iodohexa-1,5-dien-3-ol and corresponding (3R)-acetate. Removal of the acetyl group was also carried out under flow conditions by using ion exchange resin packed in a column and (3R)-(E)-1-iodohexa-1,5-dien-3-ol was obtained after simple evaporation of the eluent.
- Katayama, Sota,Koge, Tomoyuki,Katsuragi, Satoko,Akai, Shuji,Oishi, Tohru
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supporting information
p. 1116 - 1118
(2018/09/06)
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- Intramolecular cascade rearrangements of enynamine derived ketenimines: Access to acyclic and cyclic amidines
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Copper-catalyzed reaction of enynamines with sulfonylazides provides acyclic and cyclic amidines. Nucleophilic addition of the tethered amino group on the in situ generated ketenimine forms a six-membered cyclic zwitterionic intermediate which facilitates
- Chauhan, Dinesh Pratapsinh,Varma, Sreejith J.,Gudem, Mahesh,Panigrahi, Nihar,Singh, Khushboo,Hazra, Anirban,Talukdar, Pinaki
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supporting information
p. 4822 - 4830
(2017/07/10)
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- Enantioselective Allylation of β-Haloacrylaldehydes: Formal Total Syntheses of Pteroenone and Antillatoxin
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A comparative study of the catalytic allylations and crotylations of (E)- and (Z)-haloacrylaldehydes by Lewis bases (chiral N,N′-dioxides) and Br?nsted acids (chiral phosphoric acids) was undertaken. The reactions proceeded with high enantio- and diastereoselectivities with slightly better asymmetric induction observed in the case of N,N′-dioxide catalysis. The formed enantioenriched chiral unsaturated haloalcohols could be considered general building blocks, as they could be used in the syntheses of more complex natural products possessing substituted 1,3-diene fragments. This was exemplified by the formal total syntheses of pteronenone and antillatoxin. A comparative study of allylations and crotylations of (E)- and (Z)-haloacrylaldehydes is undertaken under Lewis base and Br?nsted acid catalysis. The reactions proceed in both cases with high enantio- and diastereoselectivities. The formed chiral unsaturated haloalcohols can be considered as general building blocks, as exemplified by the formal total syntheses of pteronenone and antillatoxin; HBPin = pinacolborane.
- Koukal, Petr,Ul?, Jan,Ne?as, David,Kotora, Martin
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supporting information
p. 2110 - 2114
(2016/05/09)
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- ANTIDIABETIC COMPOUNDS
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Novel compounds of the structural formula (I), and the pharmaceutically acceptable salts thereof, are agonists of G-protein coupled receptor 40 (GPR40) and may be useful in the treatment, prevention and suppression of diseases mediated by the G-protein-coupled receptor 40. The compounds of the present invention may be useful in the treatment of Type 2 diabetes mellitus, and of conditions that are often associated with this disease, including obesity and lipid disorders, such as mixed or diabetic dyslipidemia, hyperlipidemia, hypercholesterolemia, and hypertriglyceridemia.
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Page/Page column 110
(2015/09/23)
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- Cycloaddition of 1,3-dienes by visible light photocatalysis
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[2+2] Photocycloadditions of 1,3-dienes represent a powerful yet synthetically underutilized class of reactions. We report that visible light absorbing transition metal complexes enable the [2+2] cycloaddition of a diverse range of 1,3-dienes. The ability to use long-wavelength visible light is attractive because these reaction conditions tolerate the presence of sensitive functional groups that might be readily decomposed by the high-energy UVC radiation required for direct photoexcitation of 1,3-dienes. The resulting vinylcyclobutane products are poised for a variety of further diversification reactions, and this method is consequently expected to be powerfully enabling in the synthesis of complex organic targets.
- Hurtley, Anna E.,Lu, Zhan,Yoon, Tehshik P.
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supporting information
p. 8991 - 8994
(2014/09/16)
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- Practical methods for the synthesis of trifluoromethylated alkynes: Oxidative trifluoromethylation of copper acetylides and alkynes
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Two practical and complementary methods are reported for the synthesis of trifluoromethylated alkynes. The first one, a mix-and-stir process, is based on the oxidative trifluoromethylation of readily available and bench-stable copper acetylides while the second one, which displays a broad substrate scope and has several advantages over existing procedures, is based on the oxidative copper-catalyzed direct trifluoromethylation of terminal alkynes. Both reactions provide user-friendly processes for the synthesis of trifluoromethylated acetylenes which can be easily obtained from readily available starting materials.
- Tresse, Cedric,Guissart, Celine,Schweizer, Stephane,Bouhoute, Yassine,Chany, Anne-Caroline,Goddard, Mary-Lorene,Blanchard, Nicolas,Evano, Gwilherm
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supporting information
p. 2051 - 2060
(2014/07/07)
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- Palladium-catalyzed stereoretentive olefination of unactivated C(sp3)-H bonds with vinyl iodides at room temperature: Synthesis of β-vinyl α-amino acids
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A method is reported for palladium-catalyzed N-quinolyl carboxamide-directed olefination of the unactivated C(sp3)-H bonds of phthaloyl alanine with a broad range of vinyl iodides at room temperature. This reaction represents the first example of the stereoretentive installation of multisubstituted terminal and internal olefins onto unactivated C(sp3)-H bonds. These methods enable access to a wide range of challenging β-vinyl α-amino acid products in a streamlined and controllable fashion, beginning from simple precursors.
- Wang, Bo,Lu, Chengxi,Zhang, Shu-Yu,He, Gang,Nack, William A.,Chen, Gong
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supporting information
p. 6260 - 6263
(2015/02/19)
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- Palladium-catalyzed cyclization of vinyl iodide-tethered allensulfonamide
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This Letter describes a palladium-catalyzed cyclization of vinyl iodide-tethered allensulfonamide in the presence of alkylol, which provides a facile access to 2-alkoxy-3-methylene-tetrahydropyridine. The asymmetric version of this reaction has also been preliminarily realized with up to 81% enantioselectivity when chiral bisphosphine ligands were used.
- Xie, Zheng,Wu, Pan,Cai, Liangzhen,Tong, Xiaofeng
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supporting information
p. 2160 - 2162
(2014/04/03)
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- Search for highly efficient, stereoselective, and practical synthesis of complex organic compounds of medicinal importance as exemplified by the synthesis of the C21-C37 fragment of amphotericinb
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Highly stereoselective: A highly efficient, stereoselective and practical synthesis of the C21-C37 fragment of amphotericinB was realized in 25 % overall yield in eight longest linear steps from commercially available ethyl (S)-3-hydroxybutyrate by using Fráter-Seebach alkylation, Brown crotylboration, Negishi coupling, Heck reaction, and Horner-Wadsworth-Emmons (HWE) olefination as key steps (see diagram). Copyright
- Wang, Guangwei,Xu, Shiqing,Hu, Qian,Zeng, Fanxing,Negishi, Ei-Ichi
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supporting information
p. 12938 - 12942
(2013/10/01)
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- TRICYCLIC HETEROAROMATIC COMPOUNDS AS ALPHA-SYNUCLEIN LIGANDS
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Derivatives of phenothiazine, phenoxazine, and phenazine compounds and their use as α-synuclein ligands are described. Also described are methods of using these compounds and their radiolabeled analogs for the detection, monitoring, and treatment of synucleinopathies, including Parkinson's disease.
- -
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Paragraph 0159
(2013/12/04)
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- Synthesis, radiosynthesis and first in vitro evaluation of novel PET-tracers for the dopamine transporter: [11C]IPCIT and [ 18F]FE@IPCIT
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Introduction Present data indicate that merging beneficial structural elements from previously published DAT-ligands highest DAT affinity, selectivity and a suitable metabolic profile should be achieved. This combination led to the development of IPCIT and FE@IPCIT. Methods Precursor synthesis was done starting from cocaine in a six step reaction. O-[11C]-methylation was established using [11C]methyl iodide, optimized and subsequently automated. Small scale 18F-fluroroethylation as well as optimization of reaction parameters and automation were performed. Affinity and selectivity of the candidate substances were tested in standard binding experiments on human membranes. Metabolic stability and blood-brain-barrier (BBB) penetration were determined. Results Precursor compound, IPCITacid, and reference compounds, IPCIT and FE@IPCIT, were obtained in 4.9%, 12.7% and 4.1% yield, respectively. Automated radiosynthesis of [11C]IPCIT yielded 1.9 ± 0.7 GBq (12.5 ± 4%, corrected for decay). Optimum parameters for 18F-fluoroethylation were 110 C for 15 min under TBAH catalysis, yielding 67 ± 16% radiochemical incorporation. Affinity was determined as 1.7 ± 0.6 nM for IPCIT, 1.3 ± 0.2 nM for FE@IPCIT and 37 ± 13 nM for the precursor molecule, IPCIT-acid. Results from in vitro and in silico evaluations revealed high stability but also high lipophilicity. Conclusion Present data indicate high affinity and stability of both IPCIT and FE@IPCIT. Radiolabelling, optimization of reaction parameters and automation succeeded. On the other hand, data concerning BBB-penetration are not promising.
- Rami-Mark, Christina,Bornatowicz, Birgit,Fink, Cornel,Otter, Paul,Ungersboeck, Johanna,Vraka, Chrysoula,Haeusler, Daniela,Nics, Lukas,Spreitzer, Helmut,Hacker, Marcus,Mitterhauser, Markus,Wadsak, Wolfgang
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p. 7562 - 7569
(2014/01/06)
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- Synthesis and in vitro evaluation of α-synuclein ligands
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Accumulation of misfolded α-synuclein in Lewy bodies and Lewy neurites is the pathological hallmark of Parkinson's disease (PD). To identify ligands having high binding potency toward aggregated α-synuclein, we synthesized a series of phenothiazine derivatives and assessed their binding affinity to recombinant α-synuclein fibrils using a fluorescent thioflavin T competition assay. Among 16 new analogues, the in vitro data suggest that compound 11b has high affinity to α-synuclein fibrils (Ki = 32.10 ± 1.25 nM) and compounds 11d, 16a and16b have moderate affinity to α-synuclein fibrils (Ki ≈ 50-100 nM). Further optimization of the structure of these analogues may yield compounds with high affinity and selectivity for aggregated α-synuclein.
- Yu, Lihai,Cui, Jinquan,Padakanti, Prashanth K.,Engel, Laura,Bagchi, Devika P.,Kotzbauer, Paul T.,Tu, Zhude
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experimental part
p. 4625 - 4634
(2012/09/05)
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- Synthesis of E-vinyl iodides via Pd-catalyzed hydrostannation of terminal alkynes
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E-Vinyl iodides may be prepared via a one-pot reaction involving Pd-catalyzed hydrostannation of terminal alkynes followed by iodinolysis of the intermediate vinylstannane. The synthesis is tolerant of functional groups, such as alcohols and esters.
- Darwish, Alla,Chong, J. Michael
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experimental part
p. 654 - 658
(2012/01/06)
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- Total synthesis of branimycin: An evolutionary approach
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The first total synthesis of the macrolactone antibiotic branimycin (4) has been described. The key disconnection leads to a cis-dehydrodecalone core and a polyketide side chain which are connected via organometallic addition. The dehydrodecalone core was targeted via altogether five different approaches featuring various kinds of chiral elements and ring-closing methodology. In the end the most successful method starting from diepoxynaphthalene 109 was chosen to carry on with the synthesis. Thus the oxygen functions and carbon appendages were introduced via organometallic desymmetrization reactions to generate epoxy ketone 107, to which vinyl iodide 11 was added after conversion into the organolithium species. The synthesis was completed by introducing the ester side chain via Michael addition and subsequent macrolactonization. Competitive approach: The first total synthesis of the macrolactone antibiotic branimycin is described (see figure). The dehydrodecalin core was targeted via five competing approaches featuring various kinds of chiral elements and ring-closing methodology. In this "Darwinian" struggle the most successful route emerged and led to the completion of the synthesis. Copyright
- Enev, Valentin S.,Felzmann, Wolfgang,Gromov, Alexey,Marchart, Stefan,Mulzer, Johann
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supporting information; experimental part
p. 9651 - 9668
(2012/09/21)
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- Total synthesis of (+)-awajanomycin
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The total synthesis of (+)-awajanomycin has been achieved by asymmetric allylboration of a vicinal tricarbonyl compound as the key step. A substrate-controlled dihydroxylation and subsequent differentiation of diastereotopic ester groups were used to synt
- Wohlfahrt, Malte,Harms, Klaus,Koert, Ulrich
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supporting information; experimental part
p. 2260 - 2265
(2012/06/01)
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- Combinatorial synthesis of labelled drugs and PET tracers: Synthesis of a focused library of 11C-carbonyl-labelled acrylamides as potential biomarkers of EGFR expression
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Combinatorial synthesis is extensively used in drug development and lead optimisation. However, this approach has rarely been used for positron emission tomography because of limitations in available technologies. [ 11C]Carbon monoxide is amenable to combinatorial synthesis in transition-metal-catalysed reactions because it can react with a wide variety of electrophiles and nucleophiles, which opens up the possibilities for combinatorial radiochemistry. Herein, we exemplify the combinatorial approach by 11C-labelling a library of epidermal growth factor receptor inhibitors. The selection of candidates was guided by molecular docking. Epidermal growth factor receptor is overexpressed in a variety of tumours, and it has become an important drug target. The 11C-labelling reactions were performed using four substituted vinyl iodides and three different 4-anilino-6-aminoquinazolines using a palladium-mediated reaction with [ 11C]carbon monoxide using a single set of reaction conditions. In total, 12 labelled acrylamide derivatives were radiolabelled and obtained in 24-61% decay-corrected radiochemical yield (from [11C]carbon monoxide). Starting from 5.6 GBq [11C]carbon monoxide, 0.85 GBq of formulated N-[4-(3-bromo-phenylamino)-quinazolin-6-yl]-acryl[ 11C]amide [11C]12da was obtained within 47 min from end of bombardment (specific activity of 60 GBq μmol-1). This strategy is an example of how [11C]carbon monoxide can be utilised in the labelling of libraries of drug candidates and positron emission tomography tracers for in vitro and in vivo testing. Copyright
- ?berg, Ola,L?ngstr?ma, Bengt
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p. 477 - 483
(2013/03/28)
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- The vinyl moiety as a handle for regiocontrol in the preparation of unsymmetrical 2,3-aliphatic-substituted indoles and pyrroles
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Rho-Rho-Rho your boat: A rhodium catalyst effects the regioselective oxidative coupling of enynes with N-aryl ureas (X=NR2) and N-vinylacetamides (X=C(O)Me), affording the corresponding 2-alkenylindoles and 2-alkenylpyrroles in good yield. Simple hydrogenation delivers the C2/C3-aliphatic-substituted indole or pyrrole (see scheme).
- Huestis, Malcolm P.,Chan, Lina,Stuart, David R.,Fagnou, Keith
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supporting information; scheme or table
p. 1338 - 1341
(2011/04/21)
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- Highly stereoselective total synthesis of fully hydroxy-protected mycolactones A and B and their stereoisomerization upon deprotection
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Unprecedentedly efficient and highly (≥98 %) stereoselective syntheses of mycolactones A and B side chains relied heavily on Pd-catalyzed alkenylation (Negishi version) and were completed in 11 longest linear steps from ethyl (S)-3-hydroxybutyrate in 12 % and 11 % overall yield, respectively, roughly corresponding to an average of 82 % yield per step. The synthesis of mycolactone core was realized by using Pd-catalyzed alkenyl-allyl coupling and an epoxide-opening reaction with a trialkylalkenylaluminate as key steps. Fully hydroxy-protected mycolactones A and B of ≥98 % isomeric purity were synthesized successfully for the first time. However, unexpected 4:3-5:4 inseparable mixtures of mycolactones A and B were obtained upon deprotection. Copyright
- Wang, Guangwei,Yin, Ning,Negishi, Ei-Ichi
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scheme or table
p. 4118 - 4130
(2011/05/17)
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- Copper-free Sonogashira coupling of cyclopropyl iodides with terminal alkynes
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The substrate scope of the copper-free Sonogashira coupling has been successfully extended to cyclopropyl iodides, allowing an efficient access to a wide variety of functionalized alkynyl cyclopropanes.(Figure Presented)
- De Carne-Carnavalet, Benoit,Archambeau, Alexis,Meyer, Christophe,Cossy, Janin,Folleas, Benoit,Brayer, Jean-Louis,Demoute, Jean-Pierre
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supporting information; experimental part
p. 956 - 959
(2011/04/25)
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- Asymmetric synthesis of Pachastrissamine (Jaspine B) and its diastereomers via η3-allylpalladium intermediates
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A short route for the synthesis of Pachastrissamine (Jaspine B), an anhydrosphingosine derivative, and all three of its diastereomers is presented. The route consists of only 9 steps from the commercially available Garner's aldehyde. The furan framework is formed via an η3-allylpalladium intermediate.
- Passiniemi, Mikko,Koskinen, Ari M. P.
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experimental part
p. 1774 - 1783
(2011/05/04)
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- Asymmetric allylboration of vic-tricarbonyl compounds: Total synthesis of (+)-awajanomycin
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To the core: An efficient total synthesis of (+)-awajanomycin was achieved starting with an asymmetric allylboration of a vic-tricarbonyl compound (see scheme; TES=triethylsilyl). A stereoselective alkene dihydroxylation followed by a differentiation of diastereotopic ester groups and a subsequent lactamization gave the bicyclic core structure.
- Wohlfahrt, Malte,Harms, Klaus,Koert, Ulrich
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supporting information; experimental part
p. 8404 - 8406
(2011/10/31)
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- Efficient and selective syntheses of (all-E)- and (6E,10Z)-2′-O- methylmyxalamides D via Pd-catalyzed alkenylation-carbonyl olefination synergy
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(Chemical Equation Presented) Highly efficient and selective syntheses of both (all-E) and (6E,10Z)-isomers of 2′-O-methylmyxalamide D (2 and 3), in which the crucial conjugated pentaene moieties were assembled in ≥98% stereoselectivity through the use of
- Wang, Guangwei,Huang, Zhihong,Negishi, Ei-Ichi
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scheme or table
p. 3223 - 3226
(2009/05/27)
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- Stereoselective stille coupling of enantiopure haloallenes and alkenylstannanes for the synthesis of allenyl carotenoids. Experimental and computational studies
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(Chemical Equation Presented) The stereoselectivity of the Stille cross-coupling of chiral enantiopure haloallenes and alkenylstannanes en route to allenic carotenoids is shown to depend on the nature of the halogen and palladium catalyst as well as on th
- Vaz, Belen,Pereira, Raquel,Perez, Martin,Alvarez, Rosana,De Lera, Angel R.
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p. 6534 - 6541
(2008/12/22)
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- Stereoselective total synthesis of pachastrissamine (jaspine B)
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A short total synthesis of the cytotoxic natural product pachastrissamine is described. The synthesis includes eight steps starting from Garner's aldehyde and proceeds in 20% overall yield. Pd(0)-mediated intramolecular cyclisation and Ru-mediated cross-metathesis are the key reactions in this sequence.
- Passiniemi, Mikko,Koskinen, Ari M.P.
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p. 980 - 983
(2008/09/17)
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- A convenient and genuine equivalent to HZrCp2Cl generated in situ from ZrCp2Cl2-DIBAL-H
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Slow addition of 1 equiv of 1Bu2AlH to ZrCp 2Cl2 in THF provides a convenient route to either HZrCp2Cl-1Bu2AlCl (Reagent I) or HZrCp 2Cl (Reagents II and III). The latter represents a highly convenient route to genuine HZrCp2Cl, while Reagent I is useful for regio- and stereoselective conversion of 1- and 2-alkynes into (E)-1-iodo-1-alkenes and (E)-2-iodo-2-alkenes, respectively.
- Huang, Zhihong,Negishi, Ei-Ichi
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p. 3675 - 3678
(2007/10/03)
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- Stereoselective synthesis of the side chains of mycolactones A and B featuring stepwise double substitutions of 1,1-dibromo-1-alkenes
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(Chemical Equation Presented) Piecing them together: The side chains of mycolactones A and B are synthesized with a high degree of stereoselectivity. The components of the side chains are prepared separately, then combined through Pd-catalyzed cross-coupling (see scheme; Z1 = tert- butyldimethylsilyl, Z2 = methoxymethyl, TBAF = tetra-n-butylammonium fluoride).
- Yin, Ning,Wang, Guangwei,Qian, Mingxing,Negishi, Eiichi
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p. 2916 - 2920
(2007/10/03)
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- Applying asymmetric dihydroxylation to the synthesis of difluorinated carbohydrate analogues: A 1,1-difluoro-1-deoxy-d-xylulose
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Readily available difluoroenol iodides and stannanes undergo palladium-catalysed coupling reactions with alkenylstannanes and iodides, respectively, to afford a trial set of difluorinated 1,3- and 1,4-dienes, which were then exposed to AD conditions. A nu
- Cox, Liam R.,Deboos, Gareth A.,Fullbrook, Jeremy J.,Percy, Jonathan M.,Spencer, Neil
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p. 347 - 359
(2007/10/03)
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- Catalytic asymmetric synthesis of a 1-deoxy-1,1-difluoro-D-xylulose.
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[reaction: see text] A new route, of potential strategic importance, to a difluorosugar analogue has been developed. Key steps included a Stille coupling and a highly regio- and enantioselective dihydroxylation of a highly substituted diene. Protecting gr
- Cox, Liam R,DeBoos, Gareth A,Fullbrook, Jeremy J,Percy, Jonathan M,Spencer, Neil S,Tolley, Malcolm
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p. 337 - 339
(2007/10/03)
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- Dihydrobenzofuran and dihydrobenzothiophene 2,4-pentadienoic acid derivatives having selective activity for retinoid X (RXR) receptors
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Compounds of the formula where the variables have the meaning defined in the specification, are specific or selective agonists of RXR retinoid receptors.
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Page/Page column 31
(2010/01/31)
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- Triethylborane-mediated hydrogallation and hydroindation: Novel access to organogalliums and organoindiums
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Hydrogallation of carbon-carbon multiple bonds proceeds in the presence of triethylborane as a radical initiator. Several functionalities do not interfere with this reaction. Resulting alkenyl- and alkylgallium species can be trapped by several electrophiles. Highly regioselective radical addition of an indium hydride reagent to alkynes is also achieved. Various functionalities are tolerant under the reaction conditions. The reaction proceeds with complete anti stereoselectivity. Alkenylindiums obtained via hydroindation can be employed for the following cross-coupling reaction with aryl halides in one pot.
- Takami, Kazuaki,Mikami, Satoshi,Yorimitsu, Hideki,Shinokubo, Hiroshi,Oshima, Koichiro
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p. 6627 - 6631
(2007/10/03)
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- Metal-catalyzed coupling reactions on an olefin template: The total synthesis of Bupleurynol
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The naturally occurring polyacetylene Bupleurynol was synthesized in a convergent and stereospecific manner using a series of metal-mediated cross-coupling reactions. The synthesis demonstrates the utility of using a di-functional olefin template for the stereospecific synthesis of a disubstituted alkene product and its elaboration to a natural product target.
- Antunes, Luis M.,Organ, Michael G.
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p. 6805 - 6808
(2007/10/03)
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- Trans-hydrometalation of alkynes by a combination of InCl3 and DIBAL-H: One-pot access to functionalized (Z)-alkenes
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(equation presented) Triethylborane-induced hydrometalation of alkynes proceeds in an anti manner to afford the corresponding (Z)-alkenylmetal compounds stereoselectively, where dichloroindium hydride would play a key role. A variety of functional groups including hydroxy, carbonyl, and carboxy groups were tolerant under the reaction conditions. Following iodolysis and cross-coupling reaction of the (Z)-alkenylmetal species show the usefulness of this strategy.
- Takami, Kazuaki,Yorimitsu, Hideki,Oshima, Koichiro
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p. 2993 - 2995
(2007/10/03)
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- A new stereocontrolled synthesis of dihydroxerulin, a potent noncytotoxic inhibitor of the biosynthesis of cholesterol
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Dihydroxerulin, 1, has been stereoselectively synthesized by a convergent approach in which a key step was the Wittig reaction between (Z)- 5-[(E)-3-formyl-2-propenylidene]-5H-furan-2-one, 15, and the phosphonium ylid which derived from [(E)-2-decen-4,6-diyn-1-yl]triphenylphosphonium bromide, 19. Compound 19 was conveniently prepared by a short reaction sequence involving a Stille reaction between 1-trimethylstannyl-1,3-heptadiyne, 17, and (E)-3-iodo-2-propen-1-ol, 18. On the other hand, compound 15 was prepared in eight steps by a reaction sequence in which an immediate precursor to this butenolide, i.e. (Z)-5-[(2E)-4-hydroxy-2-butenylidene]-5H-furan-2-one, 34, was regio- and stereoselectively synthesized by Ag(I)-catalysed lactonization of the corresponding (Z)-2-en-4-ynoic acid. The structure and stereochemistry of 1 were established on the basis of its 1H and 13C NMR spectra at 600 and 150 MHz, respectively, and by a combination of 2D NMR techniques. (C) 2000 Elsevier Science Ltd.
- Rossi, Renzo,Bellina, Fabio,Catanese, Antonella,Mannina, Luisa,Valensin, Daniela
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p. 479 - 487
(2007/10/03)
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- Stereocontrolled synthesis of lissoclinolide by sequential transition metal-catalyzed lactonization / cross-coupling reactions
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Lissoclinolide, 1, which is an antibiotic butenolide isolated from a Tunicate, has been synthesized stereoselectively by a reaction sequence in which the Ag(I)-catalyzed lactonization of (2E,6E)-2-bromo-8-hydroxy-2,6- octadien-4-ynoic acid, (E,E)-13, and the Pd/Cu-catalyzed cross-coupling reaction of so obtained (Z)-2-bromo-5-[(E)-4-hydroxy-2-butenylidene]-5H- furan-2-one, (Z,E)-14, with (E)-3-hydroxy-1-propenyltributylstannane, 15, have been used as the key steps.
- Rossi, Renzo,Bellina, Fabio,Biagetti, Matteo,Mannina, Luisa
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p. 7799 - 7802
(2007/10/03)
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- Tetraquinane diterpenoids: Total synthesis of (±)-crinipellin B
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The total synthesis of (±)-crinipellin B (4), via a 22-step sequence of reactions starting from 2-methylcyclopent-2-en-1-one (7), is described. Three distinctly different five-membered annulation sequences (7 → 11, Scheme 1; 11 → 15, Scheme 2; 19 → 30, Scheme 4) played pivotal roles in the synthetic pathway. The constitution and relative configuration of a key synthetic intermediate, compound 32, was confirmed by an X-ray crystallographic study.
- Piers, Edward,Renaud, Johanne,Rettig, Steven J.
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p. 590 - 602
(2007/10/03)
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- Template-directed intramolecular C-glycosidation. Synthesis of the central tetrahydrofuran fragment of the elfamycin antibiotic aurodox
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A 14-step synthesis of the central tetrahydrofuran portion 4 of the elfamycin antibiotic aurodox is described, starting from the D-lyxose derivative 5. The key steps are template-directed intramolecular C-glycosidation by cation-mediated cyclisation of thioglycoside 6, and chelation-controlled addition of ethynylmagnesium bromide to aldehyde 8.
- Craig, Donald,Payne, Andrew H.,Warner, Peter
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p. 1264 - 1266
(2007/10/03)
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- Stereodefined Substituted Cyclopropyl Zinc Reagents from Gem-Bismetallics
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1,1- or n,n-Bismetallic reagents bearing a methoxymethyl ether in the γ position undergo cyclization at room temperature to give monometalated, diastereoselectively substituted cyclopropanes.The nature of the substituents is crucial for this diastereoselection, a ?-chelation between one metal and a properly located unsaturation, as well as 1,2-strain, are proposed to explain the steric outcome of these reactions.
- Beruben, Dov,Marek, Ilane,Normant, Jean F.,Platzer, Nicole
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p. 2488 - 2501
(2007/10/02)
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- Asymmetric Heck reaction of alkenyl iodides in the presence of silver salts. Catalytic asymmetric synthesis of decalin and functionalized indolizidine derivatives
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Decalin derivatives 3 (up to 80% ee) and indolizidine derivative 6 (up to 86% ee) have been synthesized by an asymmetric Heck reaction starting with prochiral alkenyl iodides 1 and 4, respectively. The important role of silver salts in the asymmetric Heck
- Sato,Nukui,Sodeoka,Shibasaki
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p. 371 - 382
(2007/10/02)
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- Inactivation of Medium-Chain Acyl-CoA Dehydrogenase by a Metabolite of Hypoglycin: Characterization of the Major Turnover Product and Evidence Suggesting an Alternative Flavin Modification Pathway
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Medium-chain acyl-CoA dehydrogenase (MCAD) is a FAD-dependent enzyme that catalyzes the first step of the fatty acid oxidation cycle.When MCAD is exposed to (methylenecyclopropyl)acetyl-CoA (MCPA-CoA), a metabolite of hypoglycin A and the causative agent of Jamaican vomiting sickness, time-dependent inactivation follows with concomitant bleaching of the active-site FAD.Earlier studies have led to the postulation that the inactivation may involve a spontaneous ring fragmentation induced by a transient α-cyclopropyl radical, and thus suggest a one-electron oxidation pathway.In an effort to find more evidence for the proposed mechanism, we have isolated and characterized the major turnover product, a CoA ester consisting of a disubstituted terminal olefin, an epoxide, and a hydroxymethyl group, from the aerobic incubation mixture of MCPA-CoA and MCAD.Formation of this product may be initiated by trapping the acyclic radical intermediate with O2 to form a transient peroxy radical which, upon receiving one electron from flavin semiquinone followed by an intramolecular epoxidation, gives rise to the observed turnover product.The identification of such a highly oxygenated species as the major turnover product strongly sustains the intermediacy of a ring-opened radical, and as such, the departure from the expected inactivation may directly result from trapping of this radical intermediate by O2.This contention was subsequently substantiated by observing that the partition ratio is nearly 0 under anaerobic incubation.Interestingly, further investigation of the anaerobic inhibition resulted in the discovery of a minor inactivation pathway involving covalent modification of flavin at a locus other than the isoalloxazine ring.Although the chemical nature of the new inhibitor-coenzyme adduct(s) has yet to be elucidated, a structure having MCPA-CoA linked to the N(10) ribityl side chain is appealing.The mechanistic insights derived from this study provide compelling evidence supporting our early notion that inactivation of MCAD by MCPA-CoA is likely to proceed through a radical mechanism.
- Lai, Ming-tain,Li, Ding,Oh, Eugene,Liu, Hung-wen
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p. 1619 - 1628
(2007/10/02)
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- A catalytic asymmetric synthesis of hydrindans
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The cis-hydrindan derivative 14b has been synthesized in up to 86% ee by an asymmetric Heck reaction starting with the prochiral alkenyl iodide 9b or the alkenyl triflate 13.
- Sato, Yoshihiro,Honda, Takahiro,Shibasaki, Masakatsu
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p. 2593 - 2596
(2007/10/02)
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- Synthesis and Properties of the Valence Tautomer of cis-Iodosocyclopropanecarboxylic Acid: 4,5-Methano-1-hydroxyiodoxol-3(1H)-one
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4,5-Methano-1-hydroxyiodoxol-3(1H)-one (4) was synthesized from propionic acid in six steps.Key reactions included Simmons-Smith cyclopropanation of cis-3-iodopropen-2-ol, followed by pyridinium dichromate oxidation to cis-iodocyclopropanecarboxylic acid.The final iodo to iodoso oxidation used either chlorination/hydrolysis or peracetic acid procedures.Compound 4 exists in the 1-hydroxyiodoxolone form, not in the "open" cis-cyclopropanecarboxylic acid form (3), as shown by its "high" pKa (7.55) and by its ability to cleave p-(nitrophenyl)diphenyl phosphate(k = 0.0044 s-1) in pH 8 aqueous micellar solution.Compound 4 disproportionates to iodo (5) and iodoxy (7) compounds in pH 8 aqueous buffer with k = 0.027 L/(M*s).Ab initio molecular orbital calculations are described which help rationalize the observed properties of 4.The reactivity of 4 (and related species) is intimately connected to the structure and bonding around the formally hypervalent iodine atom.
- Moss, Robert A.,Wilk, Boguslawa,Krogh-Jespersen, Karsten,Westbrook, John D.
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p. 6729 - 6734
(2007/10/02)
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- STEREOCONTROLLED SYNTHESIS OF NATURALLY-OCCURRING POLYACETYLENES CHARACTERIZED BY (E)-1-EN-3-YNE, (E)-1-EN-3,5-DIYNE, (1E,5E)-1,5-DIEN-3-YNE, AND (1E,7E)-1,7-DIEN-3,5-DIYNE MOIETIES
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A stereocontrolled synthesis of five naturally-occurring polyacetylenes, i.e. methyl (E)-5-(2-thienyl)-2-penten-4-ynoate, 9, (E)-N-methyl-N-(2-methylpropyl)-2-decen-4,6-diynamide, 10, (E)-1-(3-methyl-2-butenoyloxy)-2-decen-4,6-diyne, 11, (2E,6E)-1-acetoxy-2,6-decadien-4-yne, 12, and (2E,8E)-1-acetoxy-2,8-decadien-4,6-diyne, 13, is reported.The flexible strategy involves palladium(0)-copper(I) catalyzed coupling reactions to construct the carbon skeleton of the target molecules and to prepare an important C5 building block, i.e. (E)-2-penten-4-yn-1-ol, 21.This compound is also an useful intermediate to lipoxins A and B.A highly diastereoselective palladium-catalyzed carbon-carbon bond forming reaction, recently developed in our laboratory, has been used in a key synthetic step to compound 12.
- Carpita, Adriano,Neri, Dario,Rossi, Renzo
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p. 481 - 490
(2007/10/02)
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- (S)-(+)-2-(p-TOLYLSULFINYL)-2-BUTEN-4-OLIDE: AN ENANTIOMERICALLY PURE MICHAEL ACCEPTOR FOR ASYMMETRIC SYNTHESIS OF 3-SUBSTITUTED 4-BUTANOLIDES. (-)-PODORHIZON.
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A short, reliable, and practical synthesis of (S)-(+)-2-(p-tolylsulfinyl)-2-buten-4-olide has been developed, and the utility of this Michael acceptor for highly enantiocontrolled synthesis of 3-substituted 4-butanolides has been demonstrated.
- Posner, Gary H.,Kogan, Timothy P.,Haines, Stephen R.,Frye, Leah L.
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p. 2627 - 2630
(2007/10/02)
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