A ring-closing metathesis (RCM)-based approach to mycolactones A/B

The total synthesis of the mycobacterial toxins mycolactones A/B ( 1 a / b ) has been accomplished based on a strategy built around the construction of the mycolactone core through ring‐closing metathesis. By employing the Grubbs second‐generation catalyst, the 12‐membered core macrocycle of mycolactones, with a functionalized C2 handle attached to C11, was obtained in 60–80 % yield. The C‐linked upper side chain (comprising C12–C20) was completed by a highly efficient modified Suzuki coupling between C13 and C14, while the attachment of the C5‐O‐linked polyunsaturated acyl side chain was achieved by Yamaguchi esterification. Surprisingly, a diene containing a simple isopropyl group attached to C11 could not be induced to undergo ring‐closing metathesis. By employing fluorescence microscopy and flow cytometry techniques, the synthetic mycolactones A/B ( 1 a / b ) were demonstrated to display similar apoptosis‐inducing and cytopathic effects as mycolactones A/B extracted from Mycobacterium ulcerans. In contrast, a simplified analogue with truncated upper and lower side chains was found to be inactive.     

Raman spectroscopic investigations on the interactions of gastric cancer cells with 5-fluorouracil

To study the efficacy and side effects of antitumor drug by the method of Raman spectroscopy, the cancerous (SGC-7901) and normal (GES-1) gastric cells were treated with 0, 25-, 100-, and 200-mg/L 5-fluorouracil (5-Fu) for 24 h, respectively, then Raman spectra of cells were recorded. The excitation wavelength was 514.5 nm and the Raman spectra in the region of 500 - 1800 cm-1 were recorded. For the gastric cancer cells, as the concentration of 5-Fu increases, the band at 1094 cm-1 attributed to the symmetric stretching vibration mode of PO2- in the DNA backbone gradually decreases, and the intensity ratio of the band at 1315 cm-1 to that at 1340 cm-1 (I1315/I1340) shows the ascending trend, and the ratio of the band area at 1655 cm-1 to that at 1450 cm-1 (A1655/A1450) shows the slight ascending trend. For the normal gastric cells, these peaks also appear changes, however, the changes are weaker than those for the cancer cells. In SGC-7901 cells, 5-Fu can interfere with the DNA synthesis and result in the reduction of the DNA content. Besides, it can affect the unsaturation degree of the hydrocarbon chains and alter the external environment of guanine and adenine residues in cancer cells. The changes of Raman spectra for normal gastric cells reveal the side effect of 5-Fu.     

消化性溃疡急性出血120例处理体会

消化性溃疡最常见的并发症是出血，总结了消化性溃疡并急性出血住院病例１２０例处理体会，采用内镜下止血治疗，效果良好。