Synthesis, Characterization, and Anticancer Activities Evaluation of Compounds Derived from 3,4-Dihydropyrimidin-2(1H)-one.

3,4-dihydropyrimidin-2(1H)-one compounds (DHPMs) possess extensive biological activities and are mainly prepared via Biginelli reaction and N-alkylation. In the present study, selective alkylation of N¹ was investigated by using tetrabutylammonium hydroxide. In vitro cytotoxicity study on all synthesized compounds demonstrated that introduction of the aryl chain in the R³ as well as the low electron-donating group in the R¹ of DHPMs contributed to the anti-proliferative potency. A larger value of the partition coefficient (Log P) and suitable polar surface area (PSA) values were both found to be important in order to maintain the antitumor activity. The results from in vivo study indicated the great potential of compound 3d to serve as a lead compound for novel anti-tumor drugs to treat glioma. Pharmacophore study regarding the structure-activity relations of DHPMs were also conducted. Our results here could provide a guide for the design of novel bioactive 3,4-dihydropyrimidin-2(1H)-one compounds.

The Effects of Different Catalysts, Substituted Aromatic Aldehydes on One-Pot Three-Component Biginelli Reaction.

AIM AND OBJECTIVE: The Biginelli reaction, first reported in 1893, is one great example of the important multicomponent reactions reported from 1893. Under the same conditions, the influence of the common catalysts on the yield of the Biginelli reaction was investigated. MATERIALS AND METHOD: To a round-bottom flask equipped with a spherical condenser were added 1,3- dicarbonyl compound (1.0 eq), urea (1.45 eq), aromatic aldehyde (1.0 eq), catalyst and methanol. The mixture was heated at reflux for 16 h. After cooling off, the mixture was filtered and washed with cold methanol to give DHPMs. Reaction solution was further purified by recrystallization with petroleum ether and ethyl acetate. Six catalytic systems, different 1,3-dicarbonyl compounds and different substituted aromatic aldehydes with varied substitutions are described for the Biginelli reaction. An analysis was also performed to study the factors that affect the yield of the reaction. RESULTS: When 1,3-dicarbonyl compound was ethyl acetoacetate, the CuCl/ conc.H2SO4 system gave the highest yield (90.5%). While when acetoacetamide was used, the yields of DHPMs in presence of PTSA/conc. HCl, conc. HCl or FeCl3•6H2O were all over 90%. Nine DHPMs with different substituents were obtained. CONCLUSION: The Lewis acid or mixed catalyst had no significant advantage over a single protonic acid as catalyst. Conc. HCl as the catalyst was found to be the most effective condition for the preparation of DHPMs. The aromatic aldehyde with weak electron-withdrawing substituent such as Br resulted in the best yield.

Discovery, semisynthesis, biological activities, and metabolism of ocotillol-type saponins.

Ocotillol-type saponins are one kind of tetracyclic triterpenoids, sharing a tetrahydrofuran ring. Natural ocotillol-type saponins have been discovered in Panax quinquefolius L., Panax japonicus, Hana mina, and Vietnamese ginseng. In recent years, the semisynthesis of 20(S/R)-ocotillol-type saponins has been reported. The biological activities of ocotillol-type saponins include neuroprotective effect, antimyocardial ischemia, antiinflammatory, antibacterial, and antitumor activities. Owing to their chemical structure, pharmacological actions, and the stereoselective activity on antimyocardial ischemia, ocotillol-type saponins are subjected to extensive consideration. In this review, we sum up the discovery, semisynthesis, biological activities, and metabolism of ocotillol-type saponins.