While both the size of the wild population of the Pacific yew and the magnitude of the eventual demand for paclitaxel were uncertain, it was clear that an alternative, sustainable source of the natural product would be needed. Initial attempts to broaden its sourcing used needles from the tree, or material from other related Taxus species, including cultivated ones, but these attempts were challenged by the relatively low and often highly variable yields obtained. Early in the 1990s, coincident with increased sensitivity to the ecology of the forests of the Pacific Northwest, paclitaxel was successfully extracted on a clinically useful scale from these sources. Semisynthesis
Concurrently, synthetic chemists in the U.S. and France had been interested in paclitaxel, beginning in the late 1970s. As noted, by 1992 extensive efforts were underway to accomplish the total synthesis of paclitaxel, efforts motivated by the desire to generate new chemical understanding rather than to achieve practical commercial production. In contrast, the French group of Pierre Potier at the Centre national de la recherche scientifique (CNRS) addressed the matter of overall process yield, showing that it was feasible to isolate relatively large quantities of the compound 10-deacetylbaccatin from the European yew, Taxus baccata, which grew on the CNRS campus and whose needles were available in large quantity. By virtue of its structure, 10-deacetylbaccatin was seen as a viable starting material for a short semisynthesis to produce paclitaxel.
Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling asleep, the condition of being in a drowsy state due to circadian rhythm disorders, or a symptom of other health problems. It can be accompanied by lethargy, weakness and lack of mental agility.Somnolence is often viewed as a symptom rather than a disorder by itself. However, the concept of somnolence recurring at certain times for certain reasons constitutes various disorders, such as excessive daytime sleepiness, shift work sleep disorder, and others; and there are medical codes for somnolence as viewed as a disorder. Sleepiness can be dangerous when performing tasks that require constant concentration, such as driving a vehicle. When a person is sufficiently fatigued, microsleeps may be experienced. In individuals deprived of sleep, somnolence may spontaneously dissipate for short periods of time; this phenomenon is the second wind, and results from the normal cycling of the circadian rhythm interfering with the processes the body carries out to prepare itself to rest. The word "somnolence" is derived from the Latin "somnus" meaning "sleep". Causes
Circadian rhythm disorders
Circadian rhythm ("biological clock") disorders are a common cause of drowsiness as are a number of other conditions such as sleep apnea, insomnia and narcolepsy. The body clock disorders are classified as extrinsic (externally caused) or intrinsic.