482-20-2Relevant academic research and scientific papers
Design, synthesis, and anti-tobacco mosaic virus (TMV) activity of phenanthroindolizidines and their analogues
Wang, Ziwen,Wei, Peng,Wang, Lizhong,Wang, Qingmin
, p. 10212 - 10219 (2012)
On the basis of our previous structure-activity relationship (SAR) and antiviral mechanism studies, a series of phenanthroindolizidines and their analogues 3-20 were designed, targeting tobacco mosaic virus (TMV) RNA, synthesized, and systematically evaluated for their antiviral activity against TMV. The bioassay results showed that most of these compounds displayed good anti-TMV activity, and some of them exhibited higher antiviral activity than that of commercial Ningnanmycin (perhaps the most successful registered antiplant viral agent). Especially, (S)-deoxytylophorinine (5) with excellent anti-TMV activity (inactivation activity, 59.8%/500 μg mL-1 and 40.3%/100 μg mL-1; curative activity, 65.1%/500 μg mL -1 and 43.7%/100 μg mL-1; and protection activity, 70.2%/500 μg mL-1 and 51.3%/100 μg mL-1) emerged as a potential inhibitor of the plant virus. Compound 20 exhibited a strong in vivo protection effect against TMV at 100 μg mL-1, which indicated that phenanthroindolizidine analogues with a seven-membered D ring have a new and interesting structural scaffold and have great potential for further development as tobacco protection agents.
Design, synthesis and in-vitro biological evaluation of antofine and tylophorine prodrugs as hypoxia-targeted anticancer agents
Abdalla, Ashraf N.,Abdullah, Omeima,Chen, Linwei,Fischer, Peter M.,Guise, Chris P.,Liu, Yuxiu,Omran, Ziad,Patterson, Adam V.,Rauch, Cyril,Sindi, Ikhlas A.,Smaill, Jeff B.,Wang, Qingmin
, (2021/06/21)
Phenanthroindolizidines, such as antofine and tylophorine, are a family of natural alkaloids isolated from different species of Asclepiadaceas. They are characterized by interesting biological activities, such as pronounced cytotoxicity against different human cancerous cell lines, including multidrug-resistant examples. Nonetheless, these derivatives are associated with severe neurotoxicity and loss of in vivo activity due to the highly lipophilic nature of the alkaloids. Here, we describe the development of highly polar prodrugs of antofine and tylophorine as hypoxia-targeted prodrugs. The developed quaternary ammonium salts of phenanthroindolizidines showed high chemical and metabolic stability and are predicted to have no penetration through the blood–brain barrier. The designed prodrugs displayed decreased cytotoxicity when tested under normoxic conditions. However, their cytotoxic activity considerably increased when tested under hypoxic conditions.
Total synthesis of (R)-tylophorine by using an asymmetric hydrogenation of the allyl alcohol
Li, Rui,Liu, Chun-Fang,Yu, Chun-Jiao,Gu, Peiming
supporting information, p. 2170 - 2172 (2018/05/04)
An efficient synthesis of naturally occurring (R)-tylophorine is described. The alkaloid was prepared in seven steps from a known phenanthryl aldehyde with an overall yield of 14.2%. Asymmetric hydrogenation of an allyl alcohol was employed as a key step for installing a stereogenic center with good enantioselectivity (77% ee), and the ee value of the ω-chloro alcohol was improved to 95% by recrystallization. After azidation and oxidation of the enantio-enriched ω-chloro alcohol to the precursor of the Schmidt reaction, the chirality transfer in the stereospecific 1,2-migration furnished the chiral carbon in the alkaloid. Finally, a one-pot deformylation/Pictet-Spengler cyclization completed the total synthesis of (R)-tylophorine.
Two optically pure isomers of NK007 and bactericidal applications
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, (2016/10/09)
The invention relates to two optically pure isomers of NK007 for short and applications in a bactericidal aspect. Compounds NK007-3 and NK007-4 have good bactericidal activity, can be used for treating plant bacteria diseases selected from fusarium wilt of cucumber, cercospora brown spot of peanut, apple ring spot, alternaria solani, puccinia polysora, rice bakanae disease, sclerotinia rot of colza, phytophthora capsici disease, wheat sharp eyespot, bipolaris maydis, watermelon anthracnose, potato late blight, rice sheath blight disease and cucumber gray mold.
Total Synthesis of Phenanthroindolizidine Alkaloids by Combining Iodoaminocyclization with Free Radical Cyclization
Liu, Gong-Qing,Reimann, Marcel,Opatz, Till
, p. 6142 - 6148 (2016/07/26)
A concise and modular synthesis of phenanthroindolizidine alkaloids was achieved by combining iodoaminocylization with a free radical cyclization approach. The route described allowed the preparation of (±)-tylophorine, (±)-antofine, and (±)-deoxypergularinine in six steps. When commercially available l-prolinol was used as a chiral building block, (S)-(+)-tylophorine was also synthesized in 49% yield and >99% ee over five linear steps.
Two NK007 optical pure isomers and synthesis and application thereof
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, (2016/11/28)
The invention relates to two optical pure isomers called NK007 for short, synthesis thereof and application thereof in the aspects of plant virus resistance and immunoregulatory activity. Compounds NK007-1 and NK007-2 have good anti-tobacco-mosaic-virus activity, and can be used for treating plant virus diseases. The compounds NK007-1 and NK007-2 have good immunoregulatory activity and can be used for preparing medicine treating rheumatic arthritis. The method for testing the immunoregulatory activity of the compounds can be used for screening novel arthritis medicine. Please see the chemical structural formulae of the compounds in the specifications.
Asymmetric Total Synthesis of Tylophorine through a Formal [2+2] Cycloaddition Followed by Migrative Ring Opening of a Cyclobutane
Yamaoka, Yousuke,Taniguchi, Marie,Yamada, Ken-Ichi,Takasu, Kiyosei
, p. 2819 - 2825 (2015/09/15)
The asymmetric total synthesis of phenanthroindolizidine alkaloid (-)-tylophorine was achieved by asymmetric transfer hydrogenation of a cyclic imine. The cyclic imine with a pendant phenanthrene core was synthesized by a TfOH-promoted domino ring-contraction/ring-opening sequence of a cyclobutanol bearing an azide group, which was constructed by a formal [2+2] cycloaddition of a 2′-vinyl-1,1′-biaryl-2-yl ketone enolate. Catalytic asymmetric hydrogenation of the cyclic imine intermediate allowed the late-stage construction of the asymmetric center.
Short asymmetric synthesis of phenanthroindolizidines through chiral homoallylic sulfinamines
Anton-Torrecillas, Cintia,Gonzalez-Gomez, Jose C.
, p. 7018 - 7025 (2014/10/15)
An efficient stereocontrolled preparation of chiral phenanthroindolizidines is detailed. The synthesis relies on the stereoselective indium-mediated allylation of 2-(phenanthren-9-yl)acetaldehyde derivatives with chiral tert-butylsulfinamide. Chemoselecti
An enantioselective strategy for the total synthesis of (S)-tylophorine via catalytic asymmetric allylation and a one-pot DMAP-promoted isocyanate formation/Lewis acid catalyzed cyclization sequence
Su, Bo,Zhang, Hui,Deng, Meng,Wang, Qingmin
, p. 3616 - 3621 (2014/06/09)
A new asymmetric total synthesis of a phenanthroindolizidine alkaloid (S)-tylophorine is reported, which features a catalytic asymmetric allylation of aldehydes and an unexpected one-pot DMAP promoted isocyanate formation and Lewis acid catalyzed intramolecular cyclization reaction. In addition, White's direct C-H oxidation catalyst system converting monosubstituted olefins to linear allylic acetates was also employed for late-stage transformation. This journal is the Partner Organisations 2014.
Collective asymmetric synthesis of (-)-Antofine, (-)-cryptopleurine, (-)-tylophorine, and (-)-tylocrebrine with tert- butanesulfinamide as a chiral auxiliary
Zheng, Yanlong,Liu, Yuxiu,Wang, Qingmin
, p. 3348 - 3357 (2014/05/06)
A collective asymmetric synthesis of phenanthroindolizidine and phenanthroquinolizidine alkaloids (-)-antofine, (-)-cryptopleurine, (-)-tylophorine, and (-)-tylocrebrine was achieved by means of a reaction sequence involving efficient generation of chiral homoallylic amine intermediates by asymmetric allylation of the corresponding tert-butanesulfinyl imine. From these intermediates, the pyrrolidine and piperidine rings were constructed by means of an intramolecular SN2 substitution reaction and a ring-closing metathesis reaction, respectively. The unusual C5-methoxy-substituted phenanthrene moiety of (-)-tylocrebrine was generated by means of an InCl3-catalyzed cycloisomerization reaction of an o-propargylbiaryl compound.
