Asymmetric Synthesis Of β-substituted-α, γ-diamino Acids And Pyrrolidine Derivatives Containing Multichiral Centers

Part 1. The Research Process on Asymmetric Michael Addition to NitroalkenesMichael addition is one of the most powerful C-C bond-forming reactions to construct enantioenriched, highly functionalised carbon skeletons for the total synthesis of natural and biologically active compounds. Asymmetric Michael additions to nitroalkenes, which can be realized by substrate-, auxiliary- and additive-controlled reations as well as catalytic versions, were summarized in this part.Part 2. Asymmetric Synthesis ofβ-Substituted-α,γ-diamino Acids and Their DerivativesAsymmetric Michael additions to aromatic nitroalkenes with tricyclic iminolactones were achieved in this part with high stereoselectivity (dr = 20:1～>99:1) and high yields (72.2～94.8%). Optically activeβ-substituted-α,γ-diamino acids and 3-amino-2-pyrrolidinone were also gained by further transformation and manipulation of the Michael adducts. Possible mechanism of the Michael addition was proposed based on analyzing the crystal structures of the compounds (1a, 1h, 2a, 2g, 2h, 2i) and the results we have achieved. The absolute configurations of the Michael adducts were also confirmed. We provide an efficient method to synthesis p-substituted-a,y-diamino acids and their derivatives as a rusult. All of the compounds were characterized by ¹H NMR, ¹³C NMR and HRMS spectra.Part 3. Asymmetric Synthesis of Pyrrolidines Containing Mutichiral Centers via Michael-Mannich Tandem ReactionsWe optimized the Michael-Mannich tandem reaction and rationalized the process based on the asymmetric Michael addition to aliphatic nitroalkenes via iminolactones. The absolute configurations of the Michael-Mannich adducts were also confirmed according to the crystal structures of the compounds (1'k, 2'j). All of the compounds were determined by ¹H NMR, ¹³C NMR and HRMS spectra. Part 4. Synthesis of 1H-imidazo[1,2-b]-1,2,4-triazol-6-amines via multicomponent reactionA simple and effective method for the synthesis of bioactive imidazo-1,2,4-triazole analogues has been developed utilizing the MCR technique, which involved the reaction of aminoazoles, isocyanide and aldehydes. The products were characterized by ¹H NMR, ¹³C NMR, MS and elemental analysis. Interestingly, compounds 19d, 21a, 21b and 21h displayed good cytotoxic activities at 10^-4M concentration in the inhibition of tumor cell growth as evaluated by the MTT method.