6900-99-8Relevant articles and documents
A Short Total Synthesis of Benzophenanthridine Alkaloids via a Rhodium(III)-Catalyzed C-H Ring-Opening Reaction
Aravindan, Narasingan,Jeganmohan, Masilamani
, p. 14826 - 14843 (2021/10/20)
The biologically important naturally available benzophenanthridines were prepared efficiently in three steps with overall good yields. A new synthetic methodology involving a rhodium(III) catalyzed redox-neutral ring-opening of 7-azabenzonorbornadienes with aromatic aldoximes is developed to synthesize the target molecules. The developed C-H ring-opening reaction is highly diastereoselective and compatible with various sensitive functional group substituted aromatic aldoximes as well as substituted 7-azabenzonorbornadienes. The ring-opening products were transformed into highly sensitive 13,14-dehydrobenzo phenanthridine derivatives by HCl hydrolysis. Subsequently, 13,14-dehydrobenzophenanthridines were converted into biologically important benzophenanthridine alkaloids in the presence of DDQ. A possible reaction mechanism was proposed for the C-H ring-opening reaction and supported by the deuterium labeling studies.
Modular and Divergent Syntheses of Protoberberine and Protonitidine Alkaloids
Liu, Kai,Jiang, Xuefeng
supporting information, p. 1327 - 1332 (2021/03/03)
A modularly convergent and divergent strategy was established for the family synthesis of both protoberberine and protonitidine alkaloids. The robust, scalable, and flexible synthetic route featured a collective preparation of protoberberine and protonitidine alkaloids from a common isoquinoline assembled from pyridyne as the key synthon, which was based on the selective N-C or C-C cyclization via distinct processes. Through the strategy, 20 protoberberine alkaloids, 5 protonitidine alkaloids, and 11 analogues with diverse substituents were comprehensively aquired.
Method for synthesizing benzophenanthridine and protoberberine alkaloids through modular diversity regulation and control
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Paragraph 0517-0521, (2021/05/29)
The invention discloses a method for synthesizing benzophenanthridine and protoberberine alkaloids through modular diversity regulation and control. The method comprises the following steps: improving a substituent group of a high-iodine salt leaving group, generating pyridine alkyne under the action of relatively mild potassium tert-butoxide, and carrying out [4 + 2] cycloaddition reaction on the pyridine alkyne and diene to obtain polysubstituted isoquinoline ring precursor compounds. Ring opening and aromatization of the isoquinoline ring precursor are realized by developing a novel iridium-catalyzed cross-coupling method, polysubstituted isoquinoline ring compounds with connecting capacity are efficiently synthesized, and then the polysubstituted isoquinoline ring compounds are coupled with a high-activity polysubstituted cyclic boric acid to obtain 3-aryl isoquinoline high-grade intermediates. Through application of two different chemical principles, regulation and control of the 3-aryl isoquinoline high-grade intermediates are realized, and benzophenanthridine and protoberberine alkaloids are modularly, diversely and efficiently synthesized.
Merging C-H Vinylation with Switchable 6π-Electrocyclizations for Divergent Heterocycle Synthesis
Hu, Tianhui,Hua, Yuhui,Jiang, Xunjin,Qiu, Huijuan,Shen, Yang,Wu, Yifan,Xiong, Jing,Xu, Beibei,Zeng, Zhixiong,Zhang, Yandong
, p. 15585 - 15594 (2020/10/20)
Pyridinium-containing polyheterocycles exhibit distinctive biological properties and interesting electrochemical and optical properties and thus are widely used as drugs, functional materials, and photocatalysts. Here, we describe a unified two-step strategy by merging Rh-catalyzed C-H vinylation with two switchable electrocyclizations, including aza-6π-electrocyclization and all-carbon-6π-electrocyclization, for rapid and divergent access to dihydropyridoisoquinoliniums and dihydrobenzoquinolines. Through computation, the high selectivity of aza-electrocyclization in the presence of an appropriate "HCl"source under either thermal conditions or photochemical conditions is shown to result from the favorable kinetics and symmetries of frontier orbitals. We further demonstrated the value of this protocol by the synthesis of several complex pyridinium-containing polyheterocycles, including the two alkaloids berberine and chelerythrine.
Expeditious approach to pyrrolophenanthridones, phenanthridines, and benzo[ c ]phenanthridines via organocatalytic direct biaryl-coupling promoted by potassium tert -butoxide
De, Subhadip,Mishra, Sourabh,Kakde, Badrinath N.,Dey, Dhananjay,Bisai, Alakesh
, p. 7823 - 7844 (2013/09/12)
A methodology involving a "transition metal-free" intramolecular biaryl-coupling of o-halo-N-arylbenzylamines has been developed in the presence of potassium tert-butoxide and an organic molecule as catalyst. The reaction appears to proceed through KOtBu-promoted intramolecular homolytic aromatic substitution (HAS). Interestingly, this biaryl coupling also works in the presence of potassium tert-butoxide as sole promoter. On extending our approach further, we found that N-acyl 2-bromo-N-arylbenzylamines undergo a one-pot N-deprotection/biaryl coupling followed by oxidation, thus offering an expeditious route to the phenanthridine and benzo[c]phenanthridine skeletons. The strategy has been applied to a concise synthesis of Amaryllidaceae alkaloids viz. oxoassoanine (1b), anhydrolycorinone (1d), 5,6-dihydrobicolorine (2d), trispheridine (2b), and benzo[c]phenanthridines alkaloids dihydronitidine (3b), dihydrochelerythidine (3d), dihydroavicine (3f), nornitidine (3h), and norchelerythrine (3j).
Total synthesis of benzo[c]phenanthridine alkaloids based on a microwave-assisted electrocyclic reaction of the aza 6π-electron system and structural revision of broussonpapyrine
Ishihara, Yuhsuke,Azuma, Shuhei,Choshi, Tominari,Kohno, Kakujirou,Ono, Kanako,Tsutsumi, Hiroyuki,Ishizu, Takashi,Hibino, Satoshi
, p. 1320 - 1333 (2011/04/16)
Total syntheses of the des-N-methyl (nor) type of benzo[c]phenanthridine alkaloids 1a-f and 19 and benzo[c]phenanthridine alkaloids, chelerythrine (2d), and broussonpapyrine (2f) were achieved. The key step was the construction of tetracyclic 10,11-dihydrobenzo[c]phenanthridines using a microwave-assisted electrocyclic reaction of the 2-cycloalkenylbenzaldoxime methyl ether 4 as an aza 6π-electron system, which was derived in two steps from a Suzuki-Miyaura cross-coupling reaction of 2-bromobenzaldehyde 6 with 2-(3,4-dihydro-6,7- methylenedioxynaphthyl)boronic acid pinacol ester 7. In addition, the exact structure of broussonpapyrine (2f) (2,3,9,10-tetraoxygenated type) was determined to be chelerythrine (2d).
Iodine-mediated electrophilic cyclization of 2-alkynyl-1-methylene azide aromatics leading to highly substituted isoquinolines and its application to the synthesis of norchelerythrine
Fischer, Dirk,Tomeba, Hisamitsu,Pahadi, Nirmal K.,Patil, Nitin T.,Huo, Zhibao,Yamamoto, Yoshinori
supporting information; experimental part, p. 15720 - 15725 (2009/03/12)
The reaction of 2-alkynyl-1-methylene azide aromatics 1 with iodine and/or other iodium donors, such as the Barluenga reagent (Py2IBF 4/HBF4) and NIS, gave highly substituted cyclization products, namely, the 1,3-disubstituted 4-iodoisoquinolines 2, in good to high yields. Not only simple 2-alkynyl benzyl azides 1a-j and their substituted analogues 1k-u and 6 but also heteroaromatic analogues, including pyridine 8, pyrroles 10a-c, furane 10d, and thiophenes 10e-g, gave the corresponding isoquinoline derivatives in excellent to allowable yields. Electron-donating and electron-accepting substituents on the aromatic ring were equally tolerated, and either acidic or basic (or even neutral) reaction conditions, depending on the reactivity of the substrate, could be applied to smoothly convert the azide starting materials into the desired isoquinoline products in moderate to good yields. Limits were found only in connection with the substituent at the alkyne terminus, where electron-neutral or electron-donating substituents are clearly favored. The iodine-mediated electrophilic cyclization of 1 most probably proceeds through the iodonium ion intermediate 4 followed by nucleophilic cyclization of the azide and subsequent elimination of N2. This new methodology was successfully applied to the short synthesis of norchelerythrine.
Synthesis of trisphaeridine and norchelerythrine through palladium-catalyzed aryl-aryl coupling reactions
Harayama, Takashi,Akamatsu, Hisashi,Okamura, Kana,Miyagoe, Taeko,Akiyama, Toshihiko,Abe, Hitoshi,Takeuchi, Yasuo
, p. 523 - 528 (2007/10/03)
The synthesis of triphaeridine and norchelerythrine through palladium-catalyzed aryl-aryl coupling reactions was studied. The secondary amides were synthesized from 6-bromopiperonylicacid and aniline, and from piperonylic acid and 2-iodoaniline respectively, and were methoxymethylated for the preparation of starting materials for the cyclization reaction. All experiments were carried out in an argon atmosphere and the extract was washed with brine. The nuclear magnetic resonance (NMR) spectral data showed the presence of singlet signals due to aromatic proton in the products.
A versatile synthesis of fully aromatic benzo[c]phenanthridine alkaloids
Geen, Graham R.,Mann, Inderjit S.,Mullane, M. Valerie,McKillop, Alexander
, p. 9875 - 9894 (2007/10/03)
A versatile new approach for the synthesis of benzo[c]phenanthridine alkaloids is described and is illustrated by the preparation of eight different alkaloids. The key steps are Smiles rearrangements, which allow easy access to 2-bromo-1-naphthylamines from 2-bromo-1-naphthols, and the attachment of the D-ring unit by Suzuki coupling.
