- An Enantioconvergent and Concise Synthesis of Lasonolide A
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Efficient access to medicinally significant natural products is an essential basis for the development of pharmaceuticals. The limited availability of marine natural products impedes broad biological evaluation. Despite several elegant syntheses of (?)-lasonolide A having been reported, a practical synthesis of this potent anticancer polyketide remains elusive. Based on the application of borane as a traceless protecting group and the development of an unprecedented bissulfone reagent for Julia olefination, (?)-lasonolide A was assembled in an enantioconvergent manner through the application of stereoselective hydroboration, allylation, and oxidation. This concise route may provide a realistic solution for accessing derivatives and analogues.
- Yang, Lin,Lin, Zuming,Shao, Shunjie,Zhao, Qian,Hong, Ran
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- Short-route synthesis of (3E,5Z)-tetradecadienoic acid (megatomic acid), the sex attractant of the black carpet beetle
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A new and expeditious route to (3E,5Z)-3,5-tetradecadienoic acid (megatomic acid), the sex attractant of the black carpet beetle Attagenus megatoma (Fabricius), is reported which proceeds with 97% stereoselectivity; Cadiot-Chodkiewicz cross-coupling of 1-decyne and 4-bromo-3-butyn-1-ol in the presence of CuCl, followed by stereoselective reductions and Jones oxidation, gives the target molecule, with the synthetic pheromone showing a positive electrophysiological response.
- Yadav,Reddy,Ramalingam
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- Development and Mechanistic Interrogation of Interrupted Chain-Walking in the Enantioselective Relay Heck Reaction
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The formation of alkyl-palladium complexes via the nucleopalladation of alkenes is the entry point for a wide range of diverse reactions. One possibility is that the intermediate alkyl-Pd complexes can undergo a "chain-walking"event, to allow for remote functionalization through various termination processes. However, there are few methods to selectively interrupt the chain-walking process at a prescribed location. Herein, we demonstrate that a variety of homoallylic protected amines undergo an interrupted enantioselective relay Heck reaction to give enantioenriched allylic amine products. The selectivity of this process can be diverted to exclusively yield the ene-amide products by virtue of changing the nature of the amine protecting group. To rationalize this observation, we combine experiment and computation to investigate the mechanism of the chain-walking process and termination events. Isotopic labeling experiments and the computed reaction pathways suggest that the system is likely under thermodynamic control, with the selectivity being driven by the relative stability of intermediates encountered during chain-walking. These results illustrate that the chain-walking of alkyl-palladium complexes can be controlled through the alteration of thermodynamic processes and provides a roadmap for exploiting these processes in future reaction development.
- Ross, Sean P.,Rahman, Ajara A.,Sigman, Matthew S.
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- Hydrovinylation of Norbornene. Ligand-Dependent Selectivity and Asymmetric Variations
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(Equation presented) Norbornene undergoes Ni-catalyzed (1-2 mol% allylnickel bromide/phosphine/NaBARF or AgSbF6, 1 bar ethylene, -50°C) hydrovinylation (>97% yield), giving either a 1:1 or a 2:1 (norbornene/ethylene) adduct depending on the size of the phosphine. Use of binaphthol-derived phosphoramidite ligand results in up to 80% ee for the 1:1 adduct. The course of the reaction is highly dependent on the ligand (size and configuration of the appendages) and the counteranion present.
- Kumareswaran, Ramaiah,Nandi, Malay,RajanBabu
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- Stereodivergent synthesis of functionalized tetrahydropyrans accelerated by mechanism-based allylboration and bioinspired oxa-michael cyclization
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A stereodivergent strategy enabled by bioinspired oxa-Michael cyclization was developed for the synthesis of functionalized tetrahydropyrans on the basis of the inherent symmetry in 1,3-diols, the symmetries of which were tunable by stereoselective hydroboration of an allene with a variety of alkylborane reagents and subsequent allylation of an aldehyde. The mechanism-based utilization of monoalkyl borane in the hydroboration and allylation cascade is unprecedented. Symmetry breakdown: The thermodynamic and kinetic hydroboration of allenes and subsequent allylboration provide a key stereodefinable module with a latent symmetry. Following a deprotection/chain elongation/oxa-Michael cyclization sequence, the stereocogeners of highly functionalized tetrahydropyrans were synthesized for rapid access to structural motifs found in bioactive polyketides.
- Yang, Lin,Lin, Zuming,Huang, Sha-Hua,Hong, Ran
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- An epoxidation approach to a chiral lactone: Application of the Shi epoxidation
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The large-scale epoxidation of the alkene 7 with the organo-catalyst, Epoxone (10), and Oxone as the oxidant is described. This is the first large-scale application of the Shi epoxidation methodology. The large-scale preparation of the catalyst 10 is also described. The potassium salt of the unsaturated acid precursor 7 was prepared by a Suzuki coupling from 3-fluorobenzyl chloride and the vinylborane 8 derived from 4-pentynoic acid.
- Ager, David J.,Anderson, Ken,Oblinger, Eric,Shi, Yian,Vanderroest, James
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- Extension of Pd-Mediated One-Pot Ketone Synthesis to Macrocyclization: Application to a New Convergent Synthesis of Eribulin
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Recently reported Pd-mediated one-pot ketone synthesis from an unactivated alkyl bromide and a thioester has been extended to a macrocyclic ketone synthesis. In situ generation of alkylzinc halide via single electron transfer (SET), using NbCpCl4 and CrCl3, was the key for the success of macrocyclization. A new convergent synthesis of eribulin has been achieved, using (1) catalytic asymmetric Ni/Cr-mediated coupling to form the C19-C20 bond, (2) base-induced cyclization to form the methylenetetrahydrofuran ring, and (3) Pd-mediated one-pot ketone synthesis to form the macrocyclic ketone.
- Lee, Jung Hwa,Li, Zhanjie,Osawa, Ayumi,Kishi, Yoshito
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- Requirements for Lewis Acid-Mediated Capture and N-N Bond Cleavage of Hydrazine at Iron
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An iron complex bearing a pyridine(dicarbene) pincer was designed to probe the requirements of Lewis acid-enabled N2H4 capture and subsequent N-N bond cleavage. Appended boron Lewis acids were installed by two methods to circumvent the incompatibilities associated with Lewis acid/base quenching of free carbenes and boranes. N2H4 capture by borane Lewis acids is dependent on both the Lewis acidity and the steric profile about boron. A substitutionally inert primary coordination sphere at iron prevents an Fe-N2H4 interaction as well as N-N bond homolysis upon reduction.
- Kiernicki, John J.,Zeller, Matthias,Szymczak, Nathaniel K.
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- Molecular addition compounds. 13. N,N-diisopropyl-n-isobutylamine-borane: The first highly reactive trialkylamine-borane reagent for hydroborations
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N,N-Diisopropyl-N-isobutylamine (1) forms a stable liquid borane adduct (4.7 M in BH3), when diborane is bubbled into the neat amine. The adduct thus formed is stable indefinitely at room temperature under an inert atmosphere. Hydroboration studies with this new, highly reactive amine-borane adduct, H3B:NPri2Bui (2) and representative olefins, such as 1-hexene, styrene, β-pinene, cyclopentene, norbornene, cyclohexene, 2-methyl-2-butene, α-pinene, and 2,3-dimethyl-2-butene, were carried out at room temperature (22 ± 3°C) in selected solvents, tetrahydrofuran, dioxane, tert-butyl methyl ether, n-pentane, and dichloromethane. The reactions are faster in dioxane and n-pentane, requiring ~2 h for the hydroboration of simple, unhindered olefins to the trialkylborane stage.
- Brown, Herbert C.
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- First synthesis of both 1-aryl-4-[(E)-alk-1-enyl]-1H-1,2,3-triazoles and 1-aryl-4-[(Z)-1-(trimethylsilyl)alk-1-enyl]-1H-1,2,3-triazoles: assembly of π-extended 1,2,3-triazoles using a cross-coupling/click reaction sequence
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A practical and general synthetic approach to a series of π-extended 1,2,3-triazoles with both aryl and alkenyl moieties on the triazole ring is described. Synthesis of 1-aryl-4-[(E)-alk-1-enyl]-1H-1,2,3-triazoles can be achieved by the click reaction between terminal conjugated (E)-enynes, prepared by copper-mediated cross-coupling reaction of (E)-alk-1-enyldisiamylboranes with (trimethylsilyl)ethynyl bromide, and aryl azides, prepared from arylboronic acids and sodium azide in another flask and employed for the following click reaction without any purification. 1-Aryl-4-[(Z)-1-(trimethylsilyl)alk-1-enyl]-1H-1,2,3-triazoles can be also synthesized by a sequential three-step reaction, which involves copper-mediated cross-coupling reaction of (Z)-1-(trimethylsilyl)alk-1-enyldicyclohexylboranes with (trimethylsilyl)ethynyl bromide to form (Z)-1,3-bis(trimethylsilyl)alk-3-en-1-ynes, deprotection of the trimethylsilyl group on the alkynyl carbon atom to generate (Z)-3-(trimethylsilyl)alk-3-en-1-ynes and click reaction with aryl azides prepared in the same manner as described above. Both synthetic routes are tolerant of a wide range of functional groups with moderate to good yields.
- Oikawa, Asuka,Kindaichi, Gan,Shimotori, Yasutaka,Hoshi, Masayuki
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- Synthesis and biological activity of the C'D'E'F' ring system of maitotoxin
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Stereoselective synthesis of the C'D'E'F' ring system of maitotoxin was achieved starting from the E' ring through successive formation of the D' and C' rings based on SmI2-mediated reductive cyclization. Construction of the F' ring was accomplished via Suzuki-Miyaura cross-coupling with a side chain fragment and Pd(II)-catalyzed cyclization of an allylic alcohol. The C'D'E'F' ring system inhibited maitotoxin-induced Ca2+ influx in rat glioma C6 cells with an IC50 value of 59 μM.
- Kunitake, Masahiro,Oshima, Takahiro,Konoki, Keiichi,Ebine, Makoto,Torikai, Kohei,Murata, Michio,Oishi, Tohru
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- Unified Total Synthesis of Madangamines A, C, and E
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A stereodivergent strategy for the synthesis of skipped dienes is developed. The method consists of hydroboration of allenes and Migita-Kosugi-Stille coupling, which allows for access to all four possible stereoisomers of the skipped dienes. The hydroboration is especially useful for providing both E-allylic and Z-allylic alcohols from the same allene by simply changing the organoborane reagent. The strategy was successfully applied to a unified total synthesis of the madangamine alkaloids via a common ABCE-tetracyclic intermediate with a (Z,Z)-skipped diene. The late-stage variation of the D-ring enabled the supply of synthetic madangamines A, C, and E for the first time.
- Suto, Takahiro,Yanagita, Yuta,Nagashima, Yoshiyuki,Takikawa, Shinsaku,Kurosu, Yasuhiro,Matsuo, Naoya,Sato, Takaaki,Chida, Noritaka
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- Synthesis of the all-cis-trimethyldecalin fragment of unusual terpenes by radical-mediated protonolysis of an alkylboron derivative
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The synthesis of an enantiopure building-block with a contiguous all-cis-trimethyldecalin motif embedded in unusual terpenes is described. Starting from the Wieland-Miescher ketone, the key step is a one-pot hydroboration of an exocyclic methylene double bond promoted by disiamylborane and radical-mediated protonolysis of the corresponding alkylborane using 4-tert-butylcatechol.
- Villa, Giorgio,Bradshaw, Ben,Bürki, Cédric,Bonjoch, Josep,Renaud, Philippe
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- Diastereocontrolled Formal Syntheses of (±)-Lepadiformines A, B, and C and the Divergent Synthesis of 2- epi-Lepadiformine C through Unexpected Double Consecutive Epimerizations
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We describe here the diastereocontrolled formal racemic syntheses of tricyclic marine alkaloids, lepadiformines A, B, and C as well as their C2 epimers, featuring divergent and stereoselective syntheses of the N-acetyl-8a-cyanodecahydroquinoline frameworks and the base-mediated intramolecular cyclization to establish the spiral quaternary center of the tricyclic framework from sterically well-defined α-aminonitrile 2. The approach allows us to accomplish the tricyclic core structure efficiently from readily available starting materials through simple operations. An unexpected pair of consecutive epimerizations at two contiguous stereocenters is observed on the basis of single-crystal X-ray analyses of the intermediates and derivatives. The findings have been successfully applied to the total synthesis of 2-epi-lepadiformine C. The epimerization mechanism has been elucidated through a series of deuterium-labelling-controlled experiments.
- Wu, Jui-Lin,Chiou, Wen-Hua
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- The Total Synthesis of Chalcitrin
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The first total synthesis of the yellow pigment chalcitrin, a structurally distinct pulvinic acid dimer obtained from Chalciporous piperatus, has been achieved in 17 linear steps from commercially available materials. Key elements of the design include the use of a Au(I)-catalyzed Conia ene reaction and an N-heterocyclic carbene-mediated acyloin addition to rapidly fashion its unique polycyclic core, with the two high oxidation state side chains introduced in a single step via a late-stage double Stille coupling. Of note, many alternate designs based on differential final couplings failed, likely because of the hindered nature of the core. In addition, significant challenges in final natural product characterization in terms of matching NMR spectra were experienced; our studies reveal that the originally characterized material was its carboxylate salt form not its free acid.
- Yang, Ming,Yin, Fangjie,Fujino, Haruka,Snyder, Scott A.
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- (?)-Isoscopariusin A, a Naturally Occurring Immunosuppressive Meroditerpenoid: Structure Elucidation and Scalable Chemical Synthesis
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(?)-Isoscopariusin A was isolated from the aerial parts of Isodon scoparius. Chemical synthesis and spectroscopic analysis established its structure as an unsymmetrical meroditerpenoid bearing a sterically congested 6/6/4 tricyclic carbon skeleton with se
- He, Shi-Jun,Li, Ang,Li, Jian,Li, Xiao-Nian,Puno, Pema-Tenzin,Sun, Han-Dong,Yan, Bing-Chao,Zhou, Min,Zuo, Jian-Ping
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supporting information
p. 12859 - 12867
(2021/04/05)
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- Unified Total Synthesis of Madangamine Alkaloids
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The full details of a unified total synthesis of madangamine alkaloids are disclosed. Our central strategy is based on the construction of a common ABCE-tetracyclic system, followed by the late-stage installation of various D-rings. The common intermediate is assembled through N-acyliminium cyclization of a propargylsilane, and formation of the (Z,Z)-skipped diene. Stereoselective synthesis of the (Z,Z)-skipped diene is especially challenging, and is accomplished by the combination of Z-selective hydroboration of the 1,1-disubstituted allene and subsequent Migita-Kosugi-Stille coupling. Macrocyclic alkylation enables the late-stage variation of the D-rings on the common tetracyclic intermediate, resulting in the collective total syntheses of madangamines AE. The synthetic madangamine alkaloids exhibited inhibitory activities against a variety of human cancer cell lines.
- Suto, Takahiro,Yanagita, Yuta,Nagashima, Yoshiyuki,Takikawa, Shinsaku,Kurosu, Yasuhiro,Matsuo, Naoya,Miura, Kazuki,Simizu, Siro,Sato, Takaaki,Chida, Noritaka
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p. 545 - 571
(2019/04/05)
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- Stereodivergent Hydroboration of Allenes
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Full details of a stereodivergent hydroboration of allenes are reported. While hydroboration of an allene with 9-BBN provided a thermodynamically stable (E)-allylic alcohol after oxidative work-up, the reaction of an identical allene with HB(Sia)2 (disiamylborane) formed a (Z)-allylic alcohol as the kinetic product. The developed conditions allowed for the synthesis of trisubstituted olefins in a highly stereoselective fashion, which is known to be challenging. The method was also applied to the stereodivergent synthesis of structural motifs such as skipped dienes and allylbenzenes, which are often embedded in biologically active natural products.
- Nagashima, Yoshiyuki,Sasaki, Keiji,Suto, Takahiro,Sato, Takaaki,Chida, Noritaka
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supporting information
p. 1024 - 1028
(2018/03/21)
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- PALLADIUM-MEDIATED KETOLIZATION
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Provided herein are palladium-mediated coupling reactions useful in the preparation of ketone-containing organic molecules. The provided methods can be used for the preparation of natural products and pharmaceutical agents, including Eribulin, halichondrins, and analogs thereof. The present invention also provides novel halichondrin analogs which can be prepared via the palladium-mediated coupling reactions. The novel halichondrin analogs can be used in the prevention and/or treatment of diseases or conditions (e.g., proliferative diseases such as cancer).
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Paragraph 0640
(2018/06/15)
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- Photocaged Hydrocarbons, Aldehydes, Ketones, Enones, and Carboxylic Acids and Esters that Release by the Norrish II Cleavage Protocol and Beyond: Controlled Photoinduced Fragrance Release
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Five families of caged fragrance compounds that allow the storage and release of the following small volatile organic molecules are described: terpene hydrocarbons, aldehydes, ketones, Michael-type α,β-unsaturated enones, and carboxylic acids and esters. These caged molecules are released by photoexcitation via carbonyl-directed hydrogen-transfer processes and subsequent C-C bond cleavage (Norrish Type II) or by didenitrogenation of diazirines.
- Griesbeck, Axel G.,Porschen, Bj?rn,Kropf, Christian,Landes, Agnieszka,Hinze, Olga,Huchel, Ursula,Gerke, Thomas
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p. 539 - 553
(2017/01/25)
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- METHOD FOR PRODUCING CYCLOLAVANDULOL AND DERIVATIVE THEREOF
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A targeted compound is produced simply, efficiently and selectively. Specifically provided are a method for producing (2,4,4-trimethyl-2-cyclohexene)methanol, comprising the steps of: reacting the carbonyl group of 2,4,4-trimethyl-2-cyclohexenone (1) to o
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Paragraph 0082
(2016/08/29)
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- From precursor to catalyst: The involvement of [Ru(η5- Cp*)Cl2]2 in highly branch selective allylic etherification of cinnamyl chlorides
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(RuCp*Cl2)2, a general entry into Cp*Ru sandwich and half-sandwich chemistry was first used as a precatalyst in allylic etherification of cinnamyl chlorides with up to 98:2 regioselectivity (19 examples). Both the solvent effect and the exsiccant reaction condition are crucial to the reactivity and selectivity. Preliminary mechanism studies and the demonstration of Fluoxetine synthesis were presented in this work as well.
- Siddappa, Ravi Kumara Guralamatta,Chang, Chih-Wei,Chein, Rong-Jie
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supporting information
p. 1031 - 1035
(2014/02/14)
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- From precursor to catalyst: The involvement of [Ru(η5-Cp?)Cl2]2 in highly branch selective allylic etherification of cinnamyl chlorides
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(RuCp?Cl2)2, a general entry into Cp?Ru sandwich and half-sandwich chemistry was first used as a precatalyst in allylic etherification of cinnamyl chlorides with up to 98:2 regioselectivity (19 examples). Both the solvent effect and the exsiccant reaction condition are crucial to the reactivity and selectivity. Preliminary mechanism studies and the demonstration of Fluoxetine synthesis were presented in this work as well.
- Siddappa, Ravi Kumara Guralamatta,Chang, Chih-Wei,Chein, Rong-Jie
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supporting information
p. 1031 - 1035
(2015/02/19)
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- Total synthesis of taiwaniadducts B, C, and D
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The first total syntheses of taiwaniadducts B, C, and D have been accomplished. Two diterpenoid segments were prepared with high enantiopurity, both through Ir-catalyzed asymmetric polyene cyclization. A sterically demanding intermolecular Diels-Alder reaction promoted by Er(fod)3 assembled the scaffold of taiwaniadducts B and C. A carbonyl-ene cyclization forged the cage motif of taiwaniadduct D at a late stage, providing over 200 mg of this compound.
- Deng, Jun,Zhou, Shupeng,Zhang, Wenhao,Li, Jian,Li, Ruofan,Li, Ang
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supporting information
p. 8185 - 8188
(2014/06/24)
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- Synthesis of glycerol homologues
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A series of monoprotected glycerol homologues and triols were prepared in high overall yields (>90%) via the hydroboration-oxidation of the corresponding dienols. Hydroboration with disiamylborane and concomitant alkaline oxidation (NaOH, H2O2) was found to be a mild, high-yielding, and highly efficient method for the construction of a variety of glycerol homologues. Georg Thieme Verlag Stuttgart. New York.
- Thota, Kiran Kumar,Trudell, Mark L.
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p. 2280 - 2286
(2013/09/02)
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- Total synthesis of (-)-hippodamine by stereocontrolled construction of azaphenalene skeleton based on extended one-pot asymmetric azaelectrocyclization
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The first asymmetric total synthesis of (-)-hippodamine has been accomplished via the concise construction of its azaphenalene core, which is featured by the 2,4,6-chiral piperidine synthesis based on one-pot asymmetric azaelectrocyclization in the partially activated substituent system and the subsequent intramolecular Mannich reaction.
- Fujita, Shintaro,Sakaguchi, Taku,Kobayashi, Toyoharu,Tsuchikawa, Hiroshi,Katsumura, Shigeo
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supporting information
p. 2758 - 2761
(2013/07/19)
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- Synthesis of fused tetrahydropyrans by hydroalkoxylation of δ-hydroxy allenes
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Fused tetrahydropyrans were synthesized by silver(I)- and mercury(II)-mediated intramolecular hydroalkoxylations of δ-hydroxy allenes installed on a tetrahydropyran template. Cyclization of simple allenes was promoted by silver perchlorate to afford vinyl-substituted trans-fused bis-tetrahydropyrans, whereas cyclization of methyl-substituted allenes at the internal allenic carbon atom was achieved more effectively with a catalytic amount of mercuric triflate rather than with silver salts.
- Suzuki, Yumie,Kuwabara, Ayano,Koizumi, Yasuhiro,Mori, Yuji
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p. 9086 - 9095
(2013/09/24)
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- Synthesis of alcohols from m-fluorophenylsulfones and dialkylboranes: Application to the C14-C35 building block of E7389
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The reaction of m-fluorophenylsulfone anions with dialkylboranes, followed by alkaline hydroperoxide oxidation, yields alcohols in high yields. Optimization of the process, scope and limitation, and application to the synthesis of one of the C14-C35 building blocks of E7389, a right half analogue of halichondrin B, are reported.
- Liu, Lei,Henderson, James A.,Yamamoto, Akihiko,Bremond, Paul,Kishi, Yoshito
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supporting information; experimental part
p. 2262 - 2265
(2012/06/30)
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- Stereoselective synthesis of D - And L -carbocyclic nucleosides by enzymatically catalyzed kinetic resolution
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An efficient synthesis of (S)- or (R)-3-(benzyloxy-methyl)-cyclopent-3-enol was developed by appling an enzyme-catalyzed kinetic-resolution approach. This procedure allowed the syntheses of the enantiomeric building blocks (S)- and (R)-cyclopentenol with high optical purity (>98a % ee). In contrast to previous approaches, the key advantage of this procedure is that the resolution is done on the level of enantiomers that only contain one stereogenic center. Owing to this feature, it was possible to chemically convert the enantiomers into each other. By using this route, the starting materials for the syntheses of carbocyclic D- and L-nucleoside analogues were readily accessible. 3a',4a'-Unsaturated D- or L-carbocyclic nucleosides were obtained from the condensation of various nucleobases with (S)- or (R)-cyclopentenol. Functionalization of the double bond in 3a'-deoxy-3a',4a'-didehydro-carba-D- thymidine led to a variety of new nucleoside analogues. By using the cycloSal approach, their corresponding phosphorylated metabolites were readily accessable. Moreover, a new synthetic route to carbocyclic 2a'-deoxy-nucleosides was developed, thereby leading to D- and L-carba-dT. D-Carba-dT was tested for antiviral activity against multidrug-resistance HIV-1 strain E2-2 and compared to the known antiviral agent d4T, as well as L-carba-dT. Whilst L-carba-dT was found to be inactive, its D-analogue showed remarkably high activity against the resistant virus and significantly better than that of d4T. However, against the wild-type virus strain NL4/3, d4T was found to be more-active than D-carba-dT. Fighting chance: Various carbocyclic D- and L-nucleosides were synthesized from cyclopentadiene by enzyme-catalyzed kinetic resolution with high optical purity. In contrast to its L-analogue, D-carba-dT was antivirally active against multidrug-resistant HI-viruses. Copyright
- Mahler, Miriam,Reichardt, Bastian,Hartjen, Philip,Van Lunzen, Jan,Meier, Chris
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experimental part
p. 11046 - 11062
(2012/10/07)
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- Synthesis of the WXYZA' domain of maitotoxin
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A synthesis of the WXYZA' domain (7) of the marine neurotoxin maitotoxin (1) is reported. The convergent synthetic strategy involves construction of key building blocks 11 and 12, their coupling, and the elaboration of the resulting ester (10) to the targ
- Nicolaou,Baker, Thomas M.,Nakamura, Tsuyoshi
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supporting information; experimental part
p. 220 - 226
(2011/03/17)
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- Stereoselective 6-exo radical cyclization using cis-Vinyl sulfoxide: Practical total synthesis of CTX3C
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Ciguatoxins, the principal causative toxins of ciguatera seafood poisoning, are large ladder-like polycyclic ethers. We report a highly stereoselective 6-exo radical cyclization/ring-closing olefin metathesis sequence to construct the syn/trans-fused poly
- Yamashita, Shuji,Ishihara, Yuuki,Morita, Hiroyuki,Uchiyama, Junichi,Takeuchi, Katsutoshi,Inoue, Masayuki,Hirama, Masahiro
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supporting information; experimental part
p. 357 - 364
(2011/05/13)
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- Homo- and heterocoupling of terminal conjugated enynes: One-pot synthesis of alka-1,7-diene-3,5-diynes and alk-1-ene-3,5-diynes via two types of coupling reaction
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Conjugated dienediynes and enediynes with definite geometry- have been prepared in a one-pot manner. This protocol involves two types of coupling reaction, a Suzuki-type coupling and either a Hay coupling or a Cadiot-Chodkiewicz coupling. Thus, the copper
- Hoshi, Masayuki,Okimoto, Mitsuhiro,Nakamura, Shingo,Takahashi, Shinya
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experimental part
p. 3839 - 3847
(2012/01/04)
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- The first catalytic asymmetric total synthesis of ent-hyperforin
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The first catalytic asymmetric total synthesis of ent-hyperforin was described here in detail. Keys to the success were a catalytic asymmetric Diels-Alder reaction, a stereoselective Clasien rearrangement, an intramolecular aldol cyclization, and a vinylogous Pummerer rearrangement. Along with the successful synthetic route, several attempted approaches toward the construction of bicyclo[3.3.1] core and the C2 oxidation were discussed.
- Shimizu, Yohei,Shi, Shi-Liang,Usuda, Hiroyuki,Kanai, Motomu,Shibasaki, Masakatsu
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experimental part
p. 6569 - 6584
(2010/10/19)
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- One-pot synthesis of conjugated (E)-enynones via two types of cross-coupling reaction
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(Trimethylsilyl)ethynyl bromide can be easily transformed into conjugated (E)-enynones, whose skeleton consists of consecutive carbonyl, ethynyl, and (E)-ethenyl units, via a one-pot multicomponent Suzuki-type reaction-Sonogashira reaction sequence. Thus,
- Hoshi, Masayuki,Yamazaki, Hirokazu,Okimoto, Mitsuhiro
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experimental part
p. 2461 - 2464
(2010/11/18)
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- Total synthesis of (-)-brevenal: A concise synthetic entry to the pentacyclic polyether core
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(Chemical Equation Presented) Total synthesis of (-)-brevenal, a novel marine polycyclic ether natural product, is described. Highly efficient and scalable entries to the AB-ring exo-olefin and the DE-ring enol phosphate and a rapid construction of the C-
- Ebine, Makoto,Fuwa, Haruhiko,Sasaki, Makoto
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supporting information; experimental part
p. 2275 - 2278
(2009/05/11)
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- A tandem, nitroalkene conjugate addition/[3+2] cycloaddition approach to the synthesis of the pentacyclic core of (±)-scandine
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The complete pentacyclic core of the melodinus alkaloid scandine has been synthesized. The synthetic strategy features two key steps: (1) a tandem nitroalkene conjugate addition/[3+2] cycloaddition of the resulting silyl nitronate and (2) an intramolecula
- Denmark, Scott E.,Cottell, Jeromy J.
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p. 2397 - 2402
(2007/10/03)
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- Synthesis and structure of novel organocycloborates
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A series of α,ω-boryl-(bromo)alkanes of the general formula R2B-(CH2)n-Br (n = 3, 4, 5, 6) was obtained in high yield following a standard hydroboration protocol. Upon treatment with Mg turnings and formation of the respective Grignard species, all alkanes with n = 4 to 6 underwent an unprecedented boron-centered cyclisation reaction with formation of boratacyclopentanes, - hexanes, and -heptanes, respectively. All new compounds were isolated in high yields as colourless, crystalline materials and characterised in solution by multinuclear NMR spectroscopy. Four representative examples were chosen for X-ray diffraction studies, thus providing the first structurally characterised ring systems of that size at a tetraalkyl borate centre.
- Braunschweig, Holger,D'Andola, Giovanni,Welton, Tom,White, Andrew J. P.
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p. 600 - 606
(2008/09/21)
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- MUSCARINIC ACETYLCHOLINE RECEPTOR ANTAGONISTS
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Muscarinic Acetylcholine Receptor Antagonists and methods of using them are provided.
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Page/Page column 19
(2010/02/15)
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- BICYCLIC DERIVATIVES FOR THE TREATMENT OF ABNORMAL CELL GROWTH
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The invention relates to substantially pure compounds of the formula (1): and to pharmaceutically acceptable salts, prodrugs and solvates thereof, wherein R1, R2, R3, R5, and X are as defined herein, and wherein the compound of formula (1) optionally further comprises a hydroxy substituent, an O-glucuronic acid, or an N->O (N-oxide) moiety. The invention also relates to methods of treating abnormal cell growth in mammals by administering the compounds of formula (1) and to pharmaceutical compositions for treating such disorders that contain the compounds of formula (1). The invention also relates to methods of preparing the compounds of formula (1).
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Page/Page column 40-41
(2008/06/13)
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- 6R-(3,6-DIDEOXY-L-ARABINO-HEXOPYRANOSYLOXY)HEPTANOIC ACID, PREPARATION PROCESS FOR THE SAME AND DAUER EFFECT THEREOF
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The present invention relates to a determination of a stereochemistry, a synthesis and dauer effect of 6R-(3,6-dideoxy-L-arabino-hexopyranosyloxy) heptanoic acid as a pheromone isolated from the Caenorhabditis elegance related to suppress of aging and
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Page/Page column 13
(2008/06/13)
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- Stereoselective syntheses of (E)- and (Z)-1-arylalk-3-en-1-ynes and (E,E)-, (Z,E)-, (E,Z)-, and (Z,Z)-alka-1,5-dien-3-ynes via a one-pot multicomponent coupling reaction
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Both 1-arylalk-3-en-1-ynes and alka-1,5-dien-3-ynes have been synthesized under extremely mild reaction conditions in good to high yields via a sequential Suzuki-type and Sonogashira reaction in a one-pot manner. Thus, the protocol involves Cu-mediated cross-coupling reaction of (E)- or (Z)- alkenyldisiamylborane with (trimethylsilyl)ethynyl bromide in the presence of 1M NaOMe and Pd/Cu-catalyzed cross-coupling reaction with aryl or alkenyl iodide in the presence of aqueous n-Bu4NOH. The reaction with aryl iodide is tolerant of a wide variety of functional groups on the aromatic ring and leads to the stereoselective formation of (E)- and (Z)-1-arylalk-3-en-1-ynes. In addition, the reactions with (E)- and (Z)-1-iodoalk-1-enes have accomplished the construction of all possible combinations of geometrical isomers, (E,E)-, (Z,E)-, (E,Z)-, and (Z,Z)-alka-1,5-dien-3-ynes. Georg Thieme Verlag Stuttgart.
- Hoshi, Masayuki,Nakayabu, Hidenori,Shirakawa, Kazuya
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p. 1991 - 2007
(2007/10/03)
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- The hydroboration of propargyl bromide. Simple one-pot three-component routes to (Z)-1-bromoalk-1-en-4-ols and to anti-homoallylic alcohols
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The hydroboration of propargyl bromide with dialkylboranes takes place regioselectively to give 3-bromoprop-1-en-1-yl dialkylboranes 13 which, upon quaternization with bromide ion, undergo a series of transformations into a number of allylic boron species. By a suitable choice of the experimental conditions it is possible to trap the reaction intermediates with aldehydes and to steer the process toward either the synthesis of (Z)-1-bromoalk-1-en-4-ols 6 or anti-homoallylic alcohols 8. Two one-pot three-component processes were developed based on a sequence of four reactions; preparation of dialkylborane and hydroboration of propargyl bromide are the first steps. Then, quaternization with TEBABr may be carried out either in the presence of the aldehyde when (Z)-1-bromoalk-1-en-4-ols 6 are requested, or in the absence of the aldehyde in order to allow the formation of γ-substituted allyl borane 18 which, successively, adds to the aldehyde affording antihomoallylic alcohols 8.
- Lombardo,Morganti,Trombini
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p. 8767 - 8773
(2007/10/03)
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- Molecular addition compounds. 14. Convenient preparations of representative dialkylborane reagents using the new, highly reactive N- ethyl-N-isopropylaniline-borane reagent (BACH-EI(TM))
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Convenient procedures for the preparation of representative dialkylborane reagents, diisopinocampheylborane, [1S]-2-diisocaranylborane, 9-borabicyclo[3,3,1]nonane, dicyclohexylborane and disiamylborane, using the new, highly reactive N-ethyl-N-isopropylaniline-borane reagent (BACH-EI(TM)) in dioxane and tetrahydrofuran are described.
- Brown, Herbert C.,Kanth, Josyula V. B.,Zaidlewicz, Marek
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p. 5991 - 6000
(2007/10/03)
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- Molecular addition compounds. 15. Synthesis, hydroboration, and reduction studies of new, highly reactive tert-butyldialkylamine-borane adducts
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Two series of tert-butyldialkylamines have been prepared and examined for borane complexation. The complexing ability of each amine in the two series examined decreases in the order shown. First series: t- BuN(CH2CH2)2O 1a > t-BuNEt2 1b > t-BuNPr(n)21c > t-BuN(CH2CH2OMe)2 1d >> t-BuNBu(i)2 1e. Second series: t-BuNBu(i)Me 2a > t-BuNPr(i)Me 2b > t- BuNBu(i)Et 2c > t-BuNBu(i)Pr(n) 2d >>t-BuNPr(i)Et 2e. The reactivity of the corresponding borane adducts toward 1-octene increases in the reverse order. The following amines form highly reactive liquid borane adducts hydroborating 1-octene in tetrahydrofuran at room temperature in less than 1 h: t- BuN(CH2CH2OMe)2, t-BuNBu(i)Et, and t-BuNPr(i)Me. The limit of borane complexation among the amines examined is reached for t-BuNBu(i)2 exchanging borane neither with BMS nor with BH3-THF. Among the various borane adducts prepared, the more promising borane adducts, t-Bu(CH3OCH2CH2)2N-BH3 (7), t-BuMePr(i)N-BH3 (8), and t-BuEtBu(i)N-BH3 (9), were selected for complete hydroboration and reduction studies. Hydroboration studies with the new, highly reactive trialkylamine-borane adducts 7-9 and representative olefins, such as 1-hexene, styrene, β-pinene, cyclopentene, norbornene, cyclohexene, 2-methyl-2-butene, α-pinene, and 2,3-dimethyl-2-butene, in tetrahydrofuran, dioxane, tert-butyl methyl ether, n-pentane, and dichloromethane, at room temperature (22 ± 3°C) were carried out. The reactions are faster in dioxane, requiring 1-2 h for the hydroboration of simple, unhindered olefins to the trialkylborane stage. Moderately hindered olefins, such as cyclohexene and 2-methyl-2-butene, give the corresponding dialkylboranes rapidly, with further slow hydroboration. However, the more hindered olefins, α-pinene and 2,3-dimethyl-2-butene, give stable monoalkylboranes very rapidly, with further hydroboration proceeding relatively slowly. The hydroborations can also be carried out conveniently in other solvents, such as THF, tert-butyl methyl ether, and n-pentane. A significant rate retardation is observed in dichloromethane. Regioselectivity studies of 1-hexene and styrene using these amine-borane adducts show selectivities similar to that of BH3-THF. The rates and stoichiometry of the reaction of t-BuMePr(i)N-BH3 in tetrahydrofuran with selected organic compounds containing representative functional groups were also examined at room temperature. The reductions of esters, amides, and nitriles, which exhibit a sluggish reaction at room temperature, proceed readily under reflux conditions in tetrahydrofuran and dioxane and without solvent (at 85-90°C). The carrier amines can be recovered by simple acid-base manipulations in good yield and readily recycled to make the borane adducts.
- Brown, Herbert C.,Kanth, Josyula V. B.,Dalvi, Pramod V.,Zaidlewicz, Marek
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p. 6263 - 6274
(2007/10/03)
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- Addition compounds of alkali-metal hydrides. 26. Facile reaction of borinic esters with lithium monoethoxyaluminohydride to form lithium dialkylborohydrides
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Addition of 1 mol equiv of borinic esters to lithium monoethoxyaluminohydride in ethyl ether at 0°C results in a facile and rapid precipitation of the dialkoxyalane as a solid, producing the corresponding lithium dialkylborohydride in quantitative yield. The reaction is quite general, applicable to borinic esters of widely varied structural requirements. These derivatives are very stable and can be stored under nitrogen at 25 °C without hydride loss and either redistribution or isomerization of the alkyl groups. Methyl iodide or acids readily and quantitatively removes metal hydride from these dialkylborohydrides, generating the free dialkylboranes for further use. Thus the present study provides a simple method for preparing a wide variety of lithium dialkylborohydrides under mild conditions, valuable intermediates for storing dialkylboranes for extended periods of time, and a simple procedure for generating pure dialkylboranes as required for further application.
- Singaram, Bakthan,Cole, Thomas E.,Brown, Herbert C.
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p. 1520 - 1523
(2008/10/08)
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