Pd-Catalyzed Cascade Cyclization/Thiocarbonylation with Thioformates: Synthesis of Thioester-Functionalized Oxindoles.

A Pd-catalyzed thiocarbonylative cyclization of N-(o-iodoaryl)acrylamides with easily accessible thioformates has been developed. The reaction has a wide substrate scope with good yields and represents a powerful route to the synthesis of thioester-functionalized oxindoles. Both S-aryl and alkyl thioformates as the thioester sources were well tolerated. The active Pd-CO intermediate may play an important role in the transformation process.

Palladium-Catalyzed Allylation of P(O)H Compounds: Access to 2-Fluoroallylic Phosphorus Compounds.

An efficient palladium-catalyzed 2-fluoroallylation of P(O)H compounds with gem-difluorocyclopropanes is presented. The reaction provides a variety of 2-fluoroallylic phosphorus compounds in good yields with high Z selectivity through the sequential C-C bond activation, C-F bond cleavage, and C-P coupling process. Various H-phosphonates, H-phosphinates, and secondary phosphine oxides are all tolerated. In addition, the gram-scale synthesis and the late-stage modification of complex bioactive molecules show practical utilities of the transformation.

Palladium-Catalyzed Heck Cyclization with P(O)H Compounds to Construct Phosphinonyl-Azaindoline and -Azaoxindole Derivatives.

We report herein a concise method for the construction of phosphinonyl-azaindoline and -azaoxindole derivatives via a palladium-catalyzed cascade cyclization with P(O)H compounds. Various H-phosphonates, H-phosphinates, and aromatic secondary phosphine oxides are all tolerated under the reaction conditions. Furthermore, the phosphinonyl-azaindoline isomer families such as 7-, 5-, and 4-azaindolines could be synthesized in moderate to good yields.

Highly regioselective and stereoselective cascade reductive cyclization of δ-ketoamide: practical access to oxa-bridged benzazepines.

A highly regioselective and stereoselective cascade reduction cyclization of δ-ketoamide is realized under LiAlH4-assisted conditions, providing an atom-economical and straightforward approach to access oxa-bridged benzazepines in moderate to good yields. This method overcomes the limitations of aldehydes or other precursors of primary alcohols and realizes the cascade reduction cyclization of secondary alcohol anions generated in situ from ketones. The reaction proceeds with broad substrate scope and good functional group compatibility.

[Establishment of a nude mouse model of orthotopically transplanted human primary malignant lymphoma of the liver].

OBJECTIVE: To establish a nude mouse model of orthotopically transplanted human primary malignant lymphoma of the liver, and to serve researches on pathogenesis and experimental treatment of this disease. METHODS: Small pieces of lymphoma tissues freshly taken from patients with primary lymphoma of the liver were orthotopically transplanted into the liver parenchyma in nude mice. Tumorgenicity, invasion, metastasis, and morphological characteristics were examined by light and electron microscopy and immunohistochemistry. AFP, HBsAg and LDH were assayed by serological test. Karyotype analysis and DNA content of orthotopically transplanted tumors were also performed. RESULTS: A nude mouse model of orthotopically transplanted human primary malignant lymphoma of the liver was successfully established and named HLBL-0102. The tumor was confirmed as primary lymphoma of the liver (non-Hodgkin's lymphoma, B cell) by histopathology. Immunohistochemistry showed positive expression of CD19, CD20, CD45 and CD79a, but negative of CD3 and CD7. Serological test indicated that AFP was negative, HBsAg positive and the concentration of LDH was 1267.5 U/L. The number of chromosomes was between 55 and 59. DNA index (DI) was 1.57 approximately 1.61 (i.e. heteroploid). So far, the strain HLBL-0102 has grown for 3 years and been passaged for 37 generations in nude mice. Totally 283 nude mice were used for transplantation and the successful rate was 100%. Both the growth rate and resuscitation rate of liquid nitrogen cryo-preserved transplanted tumors were 100%. The transplanted tumors grew intensely and invasively in the liver of nude mice and damaged adjacent liver tissues, bile ducts and portal vein areas. No involvement of other tissues and organs and distal lymph nodes was observed. CONCLUSION: To our knowledge it is the first report of successfully established nude mouse model of orthotopically transplanted human primary malignant lymphoma of the liver. The HLBL-0102 model simulate very well the natural process of human primary lymphoma of the liver and provides an ideal animal model for researches on the biology and therapies of this malignancy.