| As an important heteroaromatic,pyridine widely exists in natural products,drugs and functional materials.Therefore,it is of great application value to develop some methods that can realize the construction of pyridine quickly and mildly.Different from the classical method for functionalization of pyridine,pyridyne could carry out double-site reaction at the same time and achieve the construction of C-X bond or C-C bond as a very active intermediate,which is a synthetic block for efficient establishment for multipoint functionalization of pyridine.Compared with precursor of benzyne,precursors for pyridyne are difficult to synthesize because of the regioselectivity and chemoselectivity of pyridine.In response to this fact,organic chemists have developed a variety of precursors of pyridyne with different initial conditions,but they still can not meet the introduction of pyridine in complex environment.Therefore,the development of one precursor with simple synthesis,mild initial conditions and good compatibility of functional group,which can adapt to the construction of pyridine in some complex scenes,has high value and prospect for application.Therefore,by screening a variety of pyridine compounds that meet the characteristics of precursor,pyridine iodonium was determined as the precursor for pyridyne,which was generated selectively through the design of leaving group,to synthesize biological or material compouds.The specific contents are as follows:(1)Modular and Divergent Syntheses of Protoberberine and Protonitidine Alkaloids via PyridyneWith the retrosynthesis analysis of two kinds of isoquinoline alkaloids,protonitidine and protoberberine alkaloids,we obtained a common synthon of polysubstituted isoquinoline,which could be constructed by the [4+2] cycloaddition reaction between pyridyne and diene.After determining the precursor,we selected substituted furan as diene and made it to obtain addition product.Then,we developed a cascade catalyzed reaction with Ir/Sc in one pot to realize the conversion of addition product to polysubstituted 3-haloisoquinoline.After 8 kinds of 3-haloisoquinoline with different substituents and 4 kinds of cyclic boric acids with different substituent were obtained,24 kinds of 3-aryl-isoquinoline were synthesized by pairwise coupling through Suzuki reaction.Then,nucleophilic reaction and 6 π electrocyclization reaction were designed to realize the construction of C-N bond and C-C respectively,and 12 kinds of protonitidine and 24 kinds of protoberberine were got controllably,of which 11 kinds of natural product were achieved for the first time,and we also took the pancreatic cancer cells known as the "king of cancer" for biological testing,getting twice the inhibition rate of Gemcitabine in 1 μmol/m L.(2)Protoberberine Derivatives applied to AIE materialsOn the basis of the first work and the effectiveness of protoberberine alkaloids as AIE molecules in the treatment of cancer,we used the existing synthetic methods to obtain protoberberine derivatives efficiently by introducing diphenylamine groups with AIE properties into the skeleton of protoberberine.It was found that the emission wavelength of berberine was shifted from 538 nm to 672 nm by fluorescence emission spectroscopy,which meant that can spread further and cause less damage to cells.And the biological activity showed that the LC50 of cervical cancer cells(Hela)was less than 2.5 μmol/m L and the LC50 of mouse embryonic cells(NIH3T3)was less than 20 μmol/m L。Therefore,this kind of berberine derivatives not only have fluorescence imaging tracking,but also have better function of killing cancer cells in the same time.(3)Controllable Pyridyne and Benzyne Generation for 氮 Doped Polycyclic Aromatic HydrocarbonsWe designed a novel cyclic iodonium as a precursor for diaryne with single molecule,controlled the release of pyridyne and benzyne based on the substrate,and then generated the second aryne under new conditions,for constructing a series of 氮 doped PAHs quickly.We investigated the selectivity of releasing aryne from the cyclic iodonium and the selectivity of nucleophilic addition to aryne.Designing diaryl and tetraaryl dienes,which reacted with precursor of diaryne through [4+2] cycloaddition,we constructed a series of PAHs.With pyridyne or benzyne from the iodide,an interesting intramolecular reaction was realized,which the benzene and naphthalene occurred [4+2] cycloaddition reaction directly.Finally,we synthesized the functional material molecule that could be treated for formal coulping with two fragment of PAHs,which provides a new method for the construction of large conjugated 氮doped PAHs. |
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