Product-Derived Bimetallic Palladium Complex Catalyzes Direct Carbonylation of Sulfonylazides.

A novel product-derived bimetallic palladium complex catalyzes a sulfonylazide-transfer reaction with the σ-donor/π-acceptor ligand CO, and is advantageous given its broad substrate scope, high efficiency, and mild reaction conditions (atmospheric pressure of CO at room temperature). This methodology provides a new approach to sulfonylureas, which are present in both pharmaceuticals and agrochemicals. The synthesis of Glibenclamide on a gram scale further revealed the practical utility of this procedure. Mechanistically, the generation of a bridged bimetallic palladium species derived from the product sulfonylurea is disclosed as the crucial step for this catalytic cycle.

Pd/C Catalyzed Carbonylation of Azides in the Presence of Amines.

A facile and efficient Pd/C-catalyzed carbonylation of both aliphatic and aromatic azides in the presence of amines is reported. Serving as the widely existed fragments in an array of biological pharmaceuticals, functionalized unsymmetrical ureas were straightforwardly synthesized by using readily available and cheap azides with amines under CO atmosphere, with the extrusion of N2 as the only byproduct. It was found that not only aryl azides but also benzyl and alkyl azides were suited for this methodology. Another feature of this procedure was the employment of a highly efficient palladium charcoal catalytic system.

Discovery of pyridine-based agrochemicals by using Intermediate Derivatization Methods.

Pyridine-based compounds have been playing a crucial role as agrochemicals or pesticides including fungicides, insecticides/acaricides and herbicides, etc. Since most of the agrochemicals listed in the Pesticide Manual were discovered through screening programs that relied on trial-and-error testing and new agrochemical discovery is not benefiting as much from the in silico new chemical compound identification/discovery techniques used in pharmaceutical research, it has become more important to find new methods to enhance the efficiency of discovering novel lead compounds in the agrochemical field to shorten the time of research phases in order to meet changing market requirements. In this review, we selected 18 representative known agrochemicals containing a pyridine moiety and extrapolate their discovery from the perspective of Intermediate Derivatization Methods in the hope that this approach will have greater appeal to researchers engaged in the discovery of agrochemicals and/or pharmaceuticals.

Concise stereoselective total synthesis of (+)-muricatacin and (+)-epi-muricatacin.

Efficient stereoselective total synthesis of (+)-muricatacin (1) and (+)-epi-muricatacin (8) was accomplished from commercially available chemical pent-4-ynoic acid via Shi's asymmetric epoxidation and Mitsunobu reaction as the key steps in 17.8% and 26.9% overall yields, respectively.

Synthesis and antifungal activity of 7-methyl-7-hydroxy-2,3-benzo[c]octa-1,6-olide.

The racemic 7-methyl-7-hydroxy-2,3-benzo[c]octa-1,6-olide, the analog of natural product (6R)-3,7-dimethyl-7-hydroxy-2-octen-1,6-olide, was totally synthesized using easily available (E)-2-(2-carboxyvinyl)benzoic acid as a raw material in nine-step reactions including three key steps of Wittig reaction, epoxidation, and cyclization, with an overall yield of 10.3%. The bioassay results showed that ( ± )-2 exhibited stronger antifungal activity than the natural product ( ± )-1 and (R)-1 against Alternaria solani with an EC50 value of 27.36 µg/ml.

Total synthesis of 3,7-dimethyl-7-hydroxy-2-octen-1,6-olide and 3,7-dimethyl-2,6-octadien-1,6-olide.

3,7-Dimethyl-7-hydroxy-2-octen-1,6-olide and 3,7-dimethyl-2,6-octadien-1,6-olide, the natural bioactive compounds isolated from the fruit of Litsea cubeba and the liverwort Plagiochila rutilans, were totally synthesized using easily available cis-geraniol as raw material in short, convenient, and low-cost, five-step reactions including three steps of oxidation, cyclization, and dehydration, with an overall yield of 47.5% and 37.3%.

[Establishment and evaluation of a bone cancer pain model].

OBJECTIVE: To explore the feasibility of a bone cancer pain model by injecting the Lewis lung carcinoma cells into the femur bone marrow cavity of C57BL/6 mice. METHODS: Sixty clear grade male C57BL/6 mice (body weight 18 approximately 20 g) were randomly divided into 4 groups(15 in each group). Cancer cell inoculated group: 2*10(6) Lewis lung carcinoma cells in 10 microL PBS were injected into the left femur bone marrow cavity, and the other 3 control groups were injected the heat inactivated Lewis cells, PBS, or a false operation respectively. Spontaneous lifting time and mechanical allodynia threshold of the mice hind paw were measured in the alternative days throughout the experiment. The structural damage of the femur was monitored by radiogram on the 7th,15th, and 23rd day respectively,and the pathohistological changes of the femur bones were observed by HE staining on the same days. RESULTS: Those mice that received intra-femur innoculation of Lewis lung carcinoma cells gradually developed the spontaneous pain, which was began on the 11th day after the innoculation, and followed by mechanical allodynia. The course of flinch lasted in the later experimental session. The 50% Von Frey threshold was significantly decreased on the 13th day after the innoculation, and the mechanical allodynia lasted the whole experimental period. On the 23rd day after the innoculation, X-ray film showed that the medullary cavity of ipsilateral distal femur was filled with tumor cells, and the cortical bone became thick; furthermore, the tumor cells invaded the peripheral muscles. CONCLUSION: Injecting the Lewis lung carcinoma cells into the femoral medullary cavity of C57BL/6 mice can successfully establish a murine bone cancer pain model, and the murine model shows much resemblance compared with the human bone cancer pain.

[Effect of different anesthesias on gastrointestinal motility after laparoscopic cholecystectomy].

OBJECTIVE: To compare the effect of three different anesthesias on gastrointestinal motility after laparoscopic cholecystectomy (LC). METHODS: Forty-two patients undergoing LC were randomly allocated to the combined epidural-general anesthesia group (Group A, n = 14), propofol-based total intravenous anesthesia group (Group B, n = 14) and isoflurane-based inhalational-intravenous general anesthesia group (Group G, n = 14). The concentration of plasma motilin was measured; the incidence of postoperative nausea and vomiting and the first flatus time were observed; and the in-hospital day was recorded. RESULTS: 1. The concentration of plasma motilin increased significantly during the first 1 h postoperatively (P < 0.05), but it had no significant difference in the 48 h after operation (P > 0.05) in comparison with the preoperative data in the three groups. The concentration of plasma motilin in Group C was much higher than that in the other two groups during the first 1 h postoperatively (P < 0.05). 2. The incidence of postoperative nausea and vomiting was much higher in Group C than that in the other two groups during the first 6 h postoperatively (P < 0.05), but there was no significant difference in the 6 h after operation in the three groups (P > 0.05). 3. The first flatus time and in-hospital day postoperatively had no statistical difference in the three groups (P > 0.05). CONCLUSION: Different anesthesias do not influence the recovery of intestinal motion and in-hospital day postoperatively; the combined epidural-general anesthesia and propofol-based total intravenous anesthesia may be ideal anesthesias because of the lower incidence of postoperative nausea and vomiting.