Natural Products cell-based

Migrastatin (192) (Scheme 37) is a novel macrolide natural product that displays an inhibitory effect on the migration of human tumor cells. After an RCM-based synthesis of the 14-membered macrolide core of 192 [94], Danishefsky also achieved the first total synthesis of the natural compound [95], using the fully functionalized tetraene 191 as the metathesis precursor. Under the conditions shown in Scheme 37, the ring-closing step proceeded (E)-selectively with exclusive participation of the two terminal double bonds in 191, delivering only the ( , ,Z)-trienyl arrangement present in 192. 

An ingenious whole-cell mechanism-based assay using an antisense fabF RNA was developed to increase the detection threshold to FabH/F inhibitors in S. aureus. A range of new natural products was thus... 

Since natural product cryptolepine hydrochloride 173 (Fig. 48) has been found to be cytotoxic to B16 melanoma cells with an IC50 of 0.3 pg/mL (1.3 pM) [102], there has also been interest in cationic 5-carboline-based compounds as antitumor agents. For example, Wright and coworkers synthesized a series of these compounds and evaluated their activity against MAC 15 cells (murine adenocarcinomas of the colon) [103]. Of the compounds prepared, the most active was 179 which had an IC50 value of 1.03 pM. 

Based upon recent controlled studies, there is considerable evidence that opioids such as morphine induce substantial effects on immune status. For example, it has been shown that morphine administration is associated with alterations in a number of immune parameters, such as natural-killer cell activity [12,13], proliferation of lymphocytes, [13, 14] antibody production [15,16], and the production of interferon [17]. Studies in our laboratory have shown that acute morphine treatment in rats suppresses splenic lymphocyte proliferative responses to both T- and B-cell mitogens, splenic natural-killer cell activity, blood lymphocyte mitogenic responsiveness to T-cell mitogens, and the in vitro production of the cytokines interleukin-2 and interferon-y [18-22], Furthermore, the immune alterations induced by morphine are dose-dependent and antagonized by the opioid-receptor antagonist, naltrexone (e.g., [22]). 

Today s rapidly increasing activities on hydrogen focus mostly on vehicle applications and less on stationary applications. For fuel cells, stationary applications are also relevant, but natural gas will be the dominant fuel here. The dominance of the transport sector is also reflected in the hydrogen roadmaps developed, among others, in the EU, the USA, Japan, or at an international level. Whereas in the beginning, onsite or decentralised production options based on fossil fuels or electricity are seen as the major option for hydrogen production, later on central production options will dominate the market. Here, several options could play a role, from coal, with carbon capture and sequestration, through natural gas and renewables (wind, biomass) to nuclear. A C02-free or lean vision can be identified in every roadmap. The cost... 

---