Zinc-Catalyzed Enantioselective Formal (3+2) Cycloadditions of Bicyclobutanes with Imines: Catalytic Asymmetric Synthesis of Azabicyclo[2.1.1]hexanes.

The cycloaddition reaction involving bicyclo[1.1.0]butanes (BCBs) offers a versatile and efficient synthetic platform for producing C(sp3)-rich rigid bridged ring scaffolds, which act as phenyl bioisosteres. However, there is a scarcity of catalytic asymmetric cycloadditions of BCBs to fulfill the need for enantioenriched saturated bicycles in drug design and development. In this study, an efficient synthesis of valuable azabicyclo[2.1.1]hexanes (aza-BCHs) by an enantioselective zinc-catalyzed (3+2) cycloadditions of BCBs with imines is reported. The reaction proceeds effectively with a novel type of BCB that incorporates a 2-acyl imidazole group and a diverse array of alkynyl- and aryl-substituted imines. The target aza-BCHs, which consist of α-chiral amine fragments and two quaternary carbon centers, are efficiently synthesized with up to 94% yield and 96.5:3.5 er under mild conditions. Experimental and computational studies reveal that the reaction follows a concerted nucleophilic ring-opening mechanism of BCBs with imines. This mechanism is distinct from previous studies on Lewis acid-catalyzed cycloadditions of BCBs.

Switching between the [2π+2σ] and Hetero-[4π+2σ] Cycloaddition Reactivity of Bicyclobutanes with Lewis Acid Catalysts Enables the Synthesis of Spirocycles and Bridged Heterocycles.

The exploration of the complex chemical diversity of bicyclo[n.1.1]alkanes and their use as benzene bioisosteres has garnered significant attention over the past two decades. Regiodivergent syntheses of thiabicyclo[4.1.1]octanes (S-BCOs) and highly substituted bicyclo[2.1.1]hexanes (BCHs) using a Lewis acid-catalyzed formal cycloaddition of bicyclobutanes (BCBs) and 3-benzylideneindoline-2-thione derivatives have been established. The first hetero-(4+3) cycloaddition of BCBs, catalyzed by Zn(OTf)2, was achieved with a broad substrate scope under mild conditions. In contrast, the less electrophilic BCB ester undergoes a Sc(OTf)3-catalyzed [2π+2σ] reaction with 1,1,2-trisubstituted alkenes, yielding BCHs with a spirocyclic quaternary carbon center. Control experiments and preliminary theoretical calculations suggest that the diastereoselective [2π+2σ] product formation may involve a concerted cycloaddition between a zwitterionic intermediate and E-1,1,2-trisubstituted alkenes. Additionally, the hetero-(4+3) cycloaddition may involve a concerted nucleophilic ring-opening mechanism.

[The analysis of hepatitis B virus genetic characterization and ratio of mutation in low-age group of HuNan].

OBJECTIVE: In order to investigate the characterization of mutation and genotype distributing in the younger group which was under the universal vaccination. The sequence of HBV was analyzed to offer the information to control and prevention in the area. METHODS: Young person's sera with positive HBsAg are collected, and the Large S sequence of HBV including preS and S gene are amplified and sequenced. The genotype and serotype were determined by clastwal with the standard genotype sequence. And one virus complete genome is amplified. RESULTS: The virus gene are successful amplified from the 33 sera. The sequence result indicate the 30 of 33 (90.9%) HBV genotype is B and 3 of 33 (9.0%) is C. The HBV serotype including ayw (1), adr (3), adw (29), 5 of 33 mutated in the "a" dominant of HBV, and the percentage is 15.2% . The HBV full length gene of serum number of 5856 is amplified and sequenced. Its genotype is B, serotype is adw and length is 3215 base. CONCLUSIONS: The dominant genotype of HuNan is B, and the dominant serotype is adw.

[Efficacy of recombinant hepatitis B vaccine and low-dose hepatitis B immune globulin in preventing mother-infant transmission of hepatitis B virus infection].

OBJECTIVE: To determine the efficacy of recombinant hepatitis B (rHB) vaccine and low-dose hepatitis B immune globulin (HBIG) in the prevention of mother-infant transmission of hepatitis B virus (HBV) infection. METHODS: rHB vaccine was administered to two groups of healthy neonates born to mothers with both hepatitis B surface antigen and e antigen positive in Guangxi, Hunan and Hebei province. Two hundred eighty-nine subjects were included in active immunization group, receiving triple doses of rHB vaccine given i.m. at 0, 1 and 6 month intervals; while 186 subjects receiving 50 IU HBIG at birth with triple doses of rHB vaccine in the low-dose HBIG group. RESULTS: Efficacy of active immunization alone was 87.8% (95% CI: 83.6 - 91.9). Efficacy of rHB vaccine and HBIG was 91.2% (95% CI: 86.7 - 95.6). No significant differences in efficacy by type of rHB vaccine (P = 0.707 2), immunoprophylaxis programs (P = 0.295 5) and regions of living (P = 0.998 7) were noticed. Seroprotection rates (anti-HBs >or= 10 mIU/ml) were detected in 91.1% and 93.5% in rHB vaccine alone recipients and rHB vaccine plus HBIG recipients, with geometric mean titer (GMT) of 153 mIU/ml and 164 mIU/ml at 1 year of age, respectively. Anti-rHBs decreased significantly with years after vaccination (chi(2) = 60.47, P = 0.000 1). Seroprotection rates of anti-rHBs antibodies decreased to 65.0% and 66.6% at 4 years of age in rHB vaccine alone recipients and rHB vaccine plus HBIG recipients, with GMT of 55 mIU/ml and 56 mIU/ml, respectively. CONCLUSION: These results suggested that the effectiveness of rHB vaccine plus low-dose HBIG was much better than only active plasma-derived vaccine; however, methods used for anti-rHBs assay need to be evaluated and verified.