Synthetic Methodology Of Phenanthroindolizidine/Quinolizidine Alkaloids And Derivatives, And Antiviral Activity Evaluation Against TMV

Phenanthroindo/quinolizidine alkaloids have attracted great attention from organic chemists and pharmacologists because of their unique structures and impressive biological activities. During our research for novel, potent, and low toxic plant virustatic agentis, we found that crude extracts from Cyanchum Komarovii AI lljinski showed excellent antiviral activity against tobacco mosic virus (TMV).The doctoral dissertation mainly focused on several aspects, which including:sodium nitrite catalyzed oxidative coupling for the construction of polymethoxylphenanthrenes, biomimic synthesis of hydroxyl-containing phenanthrenes, total synthesis of structurally unique phenanthroindo/quinolizidine alkaloids, general strategies for the total synthesis of phenanthroindo/quinolizidine alkaloids which based on cascade reaction, and design, synthesis and biological activities evaluation of structural novel derivatives of phenanthroindo/quinolizidine alkaloids and derivatives of13a/14a-substitueted phenanthroindo/quinolizidine alkaloids. Main achievements of the dissertation including:1. development of the sodium nitrite catalyzed oxidative coupling for the construction of polymethoxyphenanthrenes, and further application in the synthesis of biaryls. This oxidative system used low toxic sodium nitrite as catalyst and oxygen as terminal oxidant, which is operational simple and avoids heavy-metal contaminant to the products.2. development of the sodium nitrite catalyzed oxidative coupling for the construction of spirocyclohexadienones via biomimic manner, and acid-catalyzed spirocyclohexadienone-phenol rearrangement, which makes it easier to synthesize hydroxy-containing phenanthrenes.3. development of sodium nitrite catalyzed oxidative coupling for the construction of dihydroisoquinolinones via biomimic manner.4. the first total synthesis of enantiopure13a-methylphenanthrylindolizidine alkaloids, which features Seebach’s stereoselective alkylation and Pictet-Spengler cyclization. The route only needs eight steps from readily available compounds with35%total yields and>99%ee.5. the first total synthesis of13a-methyl-14-hydroxyphenanthrylindolizidine alkaloids, which features Seebach’s stereoselective alkylation and Parhamcyclization. The route only needs six steps from readily available compounds with30%total yields and is accessible to all of the stereoisomers.6. exploration of the first total synthesis of tyloindane via oxidative couping, Heck reaction and radical cyclization as key step respectively. The proposed structure of tyloindane was synthesized via radical cyclization as key step, and its stereoisomer was obtained via Parham cyclization as key step.7. investigation on Schmidt/Frediel-Crafts and Schmidt/Bischler-Niperalski cascade reactions, and development of the one-pot synthesis of tylophorine via Schmidt/Bischler-Niperalski/lmine-Reduction cascade reaction.8. design, synthesis and activiral activity evaluation against TMV of two kinds of structurally novel phenanthroindo/quinolizidine alkaloids analogues.9. design, synthesis and activiral activity evaluation against TMV of a series of13a/14a-substitueted phenanthroindo/quinolizidine alkaloids derivatives and analogues, most of which showed better activities than Ribavirin, and several of which were much excellent than Ningnanmycin and NK-007.