- Metal-free directed sp 2-C–H borylation
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Organoboron reagents are important synthetic intermediates that have a key role in the construction of natural products, pharmaceuticals and organic materials1. The discovery of simpler, milder and more efficient approaches to organoborons can
- Lv, Jiahang,Chen, Xiangyang,Xue, Xiao-Song,Zhao, Binlin,Liang, Yong,Wang, Minyan,Jin, Liqun,Yuan, Yu,Han, Ying,Zhao, Yue,Lu, Yi,Zhao, Jing,Sun, Wei-Yin,Houk, Kendall. N.,Shi, Zhuangzhi
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Read Online
- Synthesis of pyrrolophenanthridine alkaloids based on C(sp3)-H and C(sp2)-H functionalization reactions
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Assoanine, pratosine, hippadine, and dehydroanhydrolycorine belong to the pyrrolophenanthridine family of alkaloids, which are isolated from plants of the Amaryllidaceae species. Structurally, these alkaloids are characterized by a tetracyclic skeleton that contains a biaryl moiety and an indole core, and compounds belonging to this class have received considerable interest from researchers in a number of fields because of their biological properties and the challenges associated with their synthesis. Herein, a strategy for the total synthesis of these alkaloids by using C-H activation chemistry is described. The tetracyclic skeleton was constructed in a stepwise manner by C(sp 3)-H functionalization followed by a Catellani reaction, including C(sp2)-H functionalization. A one-pot reaction involving both C(sp3)-H and C(sp2)-H functionalization was also attempted. This newly developed strategy is suitable for the facile preparation of various analogues because it uses simple starting materials and does not require protecting groups.
- Tsukano, Chihiro,Muto, Nobusuke,Enkhtaivan, Iderbat,Takemoto, Yoshiji
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Read Online
- Electrochemical Total Synthesis of Pyrrolophenanthridone Alkaloids: Controlling the Anodically Initiated Electron Transfer Process
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Electrochemical intramolecular C(sp2)-H cross-coupling and dehydrogenative indole synthesis were developed. Both reactions were initiated by anodic oxidation of the same electron-rich indoline moiety, but the product selectivity was controlled
- Chiba, Kazuhiro,Okamoto, Kazuhiro
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supporting information
p. 3613 - 3617
(2020/04/30)
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- Construction of pyrrolophenanthridinone scaffolds mediated by samarium(II) diiodide and access to natural product synthesis
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Pyrrolophenanthridinone derivatives including the natural products were readily synthesized by samarium(II)-mediated reductive cyclization of aryl radical onto a benzene ring under mild reaction conditions. This methodology was applied to the concise synt
- Suzuki, Kenji,Iwasaki, Hiroki,Domasu, Reika,Hitotsuyanagi, Naho,Wakizaka, Yuka,Tominaga, Mao,Kojima, Naoto,Ozeki, Minoru,Yamashita, Masayuki
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p. 5513 - 5519
(2015/08/03)
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- In search of a cytostatic agent derived from the alkaloid lycorine: Synthesis and growth inhibitory properties of lycorine derivatives
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As a continuation of our studies aimed at the development of a new cytostatic agent derived from an Amaryllidaceae alkaloid lycorine, we synthesized 32 analogues of this natural product. This set of synthetic analogues included compounds incorporating sel
- Evdokimov, Nikolai M.,Lamoral-Theys, Delphine,Mathieu, Véronique,Andolfi, Anna,Frolova, Liliya V.,Pelly, Stephen C.,Van Otterlo, Willem A.L.,Magedov, Igor V.,Kiss, Robert,Evidente, Antonio,Kornienko, Alexander
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experimental part
p. 7252 - 7261
(2012/01/30)
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- Simple synthesis of pratosine and hippadine by intramolecular palladium-catalyzed cyclization and decarboxylation
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The palladium-catalyzed cyclization of dimethyl l-(2-bromo-4,5- dimethoxybenzyl)indole-2,3-dicarboxylate in the presence of tetrakis(triphenyl- phosphine)palladium(o) and potassium acetate in hot l,4-dioxane produced the 7H-pyrrolo[3,2,l-de]phenanthridine
- Umemoto, Hideaki,Dohshita, Masashi,Hamamoto, Hiromi,Miki, Yasuyoshi
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p. 1111 - 1119
(2011/06/21)
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- Simple synthesis of amides and weinreb amides Using PPh3 or PolymerSupported PPh3 and Iodine
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The combination of PPh3/I2 has been shown to be effective for the conversion of a range of carboxylic acids into secondary, tertiary, and Weinreb amides. Simplification of the procedure was possible with the use of polymer-supported PPh3/ I2. Weinreb amides produced with the use of polymer-supported PPh3 could be filtered through a short silica gel plug and used in further transformations. Thus, the use of polymer-supported PPh3 offers potential applicability to diversityoriented reactions. Formal total syntheses of apocynin and pratosine, as well as syntheses of anhydrolychorinone and hippadine, have been achieved through the use of this amide-forming method. An attempt has been made to gain insight into this reaction.
- Kumar, Amit,Akula, Hari Kiran,Lakshman, Mahesh K.
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experimental part
p. 2709 - 2715
(2010/08/05)
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- Iridium-catalyzed, silyl-directed borylation of nitrogen-containing heterocycles
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Chemical Figure Presented Selective methods for the functionalization of indoles and other nitrogen heterocycles would provide access to the core structures of many natural products and pharmaceuticals. Although there are many methods and strategies for the synthesis of substituted indoles or functionalization of the azole ring, strategies for the selective functionalization of the benzo-fused portion of the indole skeleton, particularly the 7-position, are less common. We report a one-pot, iridium-catalyzed, silyl-directed C-H borylation of indoles at the 7-position. This process occurs in high yield with a variety of substituted indoles, and conversions of the 7-borylindole products to 7-aryl-, 7-cinnamyl-, and 7-haloindoles are demonstrated. The lr-catalyzed, silyl-directed C-H borylation also occurs with several other nitrogen heterocycles, including carbazole, phenothiazines, and tetrahydroquinoline. The utility of this methodology is highlighted by the one-pot synthesis of a member of the pyrrolophenanthrldone class of alkaloid natural products. Copyright
- Robbins, Daniel W.,Boebel, Timothy A.,Hartwig, John F.
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supporting information; experimental part
p. 4068 - 4069
(2010/05/01)
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- Comparative study of the Kumada, Negishi, Stille, and Suzuki - Miyaura reactions in the synthesis of the indole alkaloids hippadine and pratosine
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The total synthesis of hippadine by a tandem metalation/cross-coupling/ lactamization strategy was investigated starting from either 7-bromoindole or a 6-halogenated methyl piperonate. The Kumada and Negishi cross-coupling reactions failed to provide any of the desired product. However, the Stille and Suzuki reactions furnished hippadine in low yields starting from the electron-deficient methyl 6-iodo- and 6-bromopiperonate, respectively. Starting from the metalated indole, only the Suzuki reaction occurred, affording hippadine in 67-74% and pratosine in 62% isolated yield.
- Mentzel, Uffe V.,Tanner, David,Tonder, Janne E.
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p. 5807 - 5810
(2007/10/03)
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- A domino amidation route to indolines and indoles: Rapid syntheses of anhydrolycorinone, hippadine, oxoassoanine, and pratosine
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(Chemical Equation Presented) When subjected to palladium-catalyzed amidation conditions, 2-triflyloxy phenethyl carbonates undergo, in addition to the expected aryl cross-coupling, an additional amidation with net displacement of the carbonate. The result is a one-step synthesis of indolines which may be oxidized to indoles. The utility of the procedure is illustrated by the two- or three-step syntheses of anhydrolycorinone, hippadine, oxoassoanine, and pratosine.
- Ganton, Michael D.,Kerr, Michael A.
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p. 4777 - 4779
(2007/10/03)
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- Development of an Efficient Procedure for Indole Ring Synthesis from 2-Ethynylaniline Derivatives Catalyzed by Cu(II) Salts and Its Application to Natural Product Synthesis
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The development of efficient methods for the indole synthesis catalyzed by Cu(II) salts and its applications were investigated. Cu(OAc)2 has been proved to be the best catalyst for the synthesis of various 1-p-tolylsulfonyl or 1-methylsulfonylindoles, which have both electron-withdrawing and electron-donating groups on the aromatic ring and C2 position of indoles. For the primary aniline derivatives, Cu(OCOCF 3)2 showed good activities, while Cu(OAc)2 was a good catalyst for the cyclization of secondary anilines. This methodology could be applied to the sequential cyclization reaction for the compounds which have the electrophilic part in the same molecule. By prior treatment with KH, the sequential cyclization was realized to provide the tricyclic ring systems, but it was limited to five- and six-membered rings for the second cyclization. Finally, formal and total synthesis of hippadine with the Cu(II)-promoted indole synthesis as the key step was accomplished.
- Hiroya, Kou,Itoh, Shin,Sakamoto, Takao
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p. 1126 - 1136
(2007/10/03)
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- Application of a catalytic palladium biaryl synthesis reaction, via C-H functionalization, to the total synthesis of Amaryllidaceae alkaloids
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The total synthesis of the Amaryllidaceae alkaloids dehydroanhydrolycorine, hippadine, pratosine, anhydrolycorine, assoanine, anhydrolycorin-7-one and oxoassoanine was achieved from the appropriate N-benzylisatin precursors using an intramolecular, palladium catalyzed, dehydrohalogenation, biaryl synthesis reaction to establish the carbon skeleton of the natural products. In order to avoid the formation of regioisomers in the cyclization reactions it was found necessary to incorporate the halogen on the benzyl group. Borane reduction of the 7H-pyrrolo[3,2,1-de]phenanthridine-4,5-dione derivatives gave 7H-pyrrolo[3,2,1-de]- and 4,5-dihydro-7H-pyrrolo[3,2,1-de]-phenanthridines (dehydroanhydrolycorine, dehydroassoanine, anhydrolycorine and assoanine). The former were readily reduced to the latter with NaCNBH3 to give anhydrolycorine and assoanine. These compounds were then oxidized to anhydrolycorin-7-one and oxoassoanine whilst the same mixtures of borane reduction products could be oxidized to give hippadine and pratosine. N-benzylisatin derivatives (5) were used as masked indoles that were transformed into pyrrolo[3,2,1-de]phenanthridinone derivatives (1 or 2) in a concise manner via C-H functionalization, involving a palladium catalysed dehydrohalogenation reaction, followed by reduction and oxidation reactions.
- Torres, José C.,Pinto, Angelo C.,Garden, Simon J.
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p. 9889 - 9900
(2007/10/03)
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- Directed ortho metalation approach to C-7-substituted indoles. Suzuki-Miyaura cross coupling and the synthesis of pyrrolophenanthridone alkaloids
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(Matrix presented) Although the indole N-phosphinoyl derivative 4 undergoes n-BuLi deprotonation/electrophile quench to afford C-7-substituted products, its deprotection requires harsh conditions. On the other hand, the N-amide 12, upon sequential or one-pot C-2 metalation, silylation, C-7 metalation, and electrophile treatment, furnishes indoles 7 in good overall yields. In combination with the Suzuki-Miyaura protocol, C-7 aryl (heteroaryl)-substituted indoles 14 and 16 are obtained, including hippadine and pratosine, members of the pyrrolophenanthridone alkaloid family.
- Hartung, Christian G.,Fecher, Anja,Chapell, Brian,Snieckus, Victor
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p. 1899 - 1902
(2007/10/03)
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- Transition metal complexes in organic synthesis, part 69. Total synthesis of the Amaryllidaceae alkaloids anhydrolycorinone and hippadine using iron-and palladium-mediated coupling reactions
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A novel synthesis of the Amaryllidaceae alkaloids anhydrolycorinone and hippadine has been developed using an iron-mediated oxidative alkylamine cyclization and an intramolecular palladium-mediated biaryl coupling as the key steps.
- Kn?lker, Hans-Joachim,Filali, Salima
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p. 1752 - 1754
(2007/10/03)
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- Total synthesis of Amaryllidaceae alkaloids utilizing sequential intramolecular heterocyclic azadiene Diels-Alder reactions of an unsymmetrical 1,2,4,5-tetrazine
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Convergent total syntheses of anhydrolycorinone, hippadine, and anhydrolycorinium chloride are detailed, enlisting sequential inverse electron demand Diels-Alder reactions of an unsymmetrical N-acyl-6-amino-1,2,4,5-tetrazine.
- Boger,Wolkenberg
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p. 9120 - 9124
(2007/10/03)
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- Intramolecular palladium-catalyzed cyclization of methyl 1-(2- bromobenzyl)indole-2-carboxylates: Synthesis of pratosine and hippadine
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Palladium-catalyzed cyclization of methyl 1-(2-bromo-4,5-dimethoxy- benzyl)indole-2-carboxylate in the presence of potassium acetate in hot 1,4- dioxane gave a 7H-pyrrolo[3,2,1-de]phenanthridine derivative, which was converted to pratosine in four steps.
- Miki, Yasuyoshi,Shirokoshi, Hideaki,Matsushita, Ko-ichi
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p. 4347 - 4348
(2007/10/03)
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- A short synthesis of hippadine
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A synthesis of the pyrrolophenanthridone alkaloid hippadine is described. The approach features the use of a low temperature Ullman type coupling reaction to effect construction of the pentacyclic skeleton and an unusual methylene oxidation promoted by barium manganate.
- Harrowven, David C.,Lai, Darren,Lucas, Matthew C.
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p. 1300 - 1302
(2007/10/03)
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- A new approach to pyrrolophenanthridone alkaloids via intramolecular radical cyclization
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A new approach to the synthesis of pyrrolophenanthridone class of alkaloids is described. The method is based on intramolecular radical cyclization of easily accessible 1-aroyl-7-bromoindoles with Bu3SnH and AIBN.
- Tsuge, Otohiko,Hatta, Taizo,Tsuchiyama, Hiroshi
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p. 155 - 156
(2007/10/03)
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- An oxazoline-mediated synthesis of the pyrrolophenanthridine alkaloids and some novel derivatives
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An unsymmetrical biaryl coupling between the Grignard of N-benzyl-7-bromoindoline 25 and the appropriately substituted (o-methoxyaryl)oxazoline 15 leads to an intermediate biaryl which can be elaborated in one step to the 1H-pyrrolo[3,2,1-de]phenanthridine ring system. This simple two-step sequence provides general access to the pyrrolophenanthridine alkaloids 2-6.
- Hutchings, Richard H.,Meyers
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p. 1004 - 1013
(2007/10/03)
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- A Synthesis of Pyrrolophenanthridone Alkaloids via Consecutive Directed Lithiation and Palladium -Catalyzed Cross-Coupling Reactions
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A short and convergent synthesis of pyrrolophenanthridone alkaloids, such as anhydrolycorin-7-one, oxoassoanine, hippadine, and pratosine, was developed by using directed lithiation and palladium-catalyzed cross-coupling as key reactions.Anhydrolycorin-7-
- Iwao, Masatomo,Tekehara, Hirokazu,Obata, Shigeru,Watanabe, Mitsuaki
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p. 1717 - 1720
(2007/10/02)
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- Palladium catalysed intramolecular coupling of aryl and benzylic halides and related tandem cyclisations. A simple synthesis of hippadine
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A Pd(0)/R3Sn)2 (R=Me or n-Bu) catalyst system effects intramolecular aryl-aryl, benzyl-aryl, benzyl-benzyl coupling of aryl and benzyl halides in good yield. Polycyclisations can be achieved by relaying the coupling via an alkene or alkyne "linker". The methodology is exemplified by a short synthesis of hippadine.
- Grigg, Ronald,Teasdale, Andrew,Sridharan, Visuvanathar
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p. 3859 - 3862
(2007/10/02)
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- Total synthesis of the amaryllidaceae alkaloid ungeremine
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The synthesis of the aromatic Amaryllidaceae alkaloid ungeremine 1 with a new type of radical cyclisation as the key step is reported.
- Lauk, Urs,Duerst, Doris,Fischer, Walter
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- Concise syntheses of the amaryllidaceae alkaloids ungerimine and hippadine via the suzuki aryl-aryl cross coupling reaction
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Short syntheses of the betaine alkaloid ungerimine (1) and the lactam alkaloid hippadine (4) based on aryl boronic acid - aryl halide cross coupling methodology are described.
- Siddiqui,Snieckus
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p. 1523 - 1526
(2007/10/02)
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- A DIRECT SYNTHESIS OF PYRROLOPHENANTHRIDONE ALKALOIDS
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Pyrrolophenanthridone alkaloids were easily synthesized by palladium acetate catalyzed arylation of N-acylindolines (5a-c) followed by dehydrogenation.
- Black, David St C.,Keller, Paul A.,Kumar, Naresh
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p. 5807 - 5808
(2007/10/02)
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- OCCURRENCE OF TWO EPIMERIC ALKALOIDS AND METABOLISM COMPARED WITH LYCORINE IN CRINUM LATIFOLIUM
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Two new epimeric pyrrolophenanthridine alkaloids, 2-epilyocorine and 2-epipancrassidine, were isolated from the flower-stem fluid of Crinum latifolium.The structures of the two alkaloids were established by spectroscopic analyses, crucial chemical transformation, and synthesis in case of the former.The differences in the metabolic pathways of lycorine and 2-epilycorine were studied under simulated physiological conditions and their biochemical significance was appraised.Key Word Index - Crinum latifolium; Amaryllidaceae; epimeric alkaloids; 2-epilycorine; 2-epipancrassidine, metabolic pathways; biochemical significance.
- Ghosal, Shibnath,Unnikrishnan, Sankara,Singh, Sushil K.
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p. 2535 - 2537
(2007/10/02)
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