The First Surveys

FIGURE 2 Map of Uhuru cosmic X-ray sources plotted in galactic coordinates and showing the relative intensity and source type for several major classes of source. 

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Recently Stroebel et al. published the first survey of Internet sites relating to various aspects of luminescence [56], In their classification they cite relevant companies and existing products, general websites, images, movies, and demonstrations for educational purposes. Below are summarized some of these useful websites to which others have been added. 

The first surveys were started in 1994, setting out to find an alternative process. Enormous amounts of work were completed by Akzo Nobel Research departments to examine the various alternatives. All results were judged on their merits. 

The interesting biological activities reported for pyrazolopyrimidines have stimulated chemists to develop the chemistry of this class of compounds. In the last 20 years, an enormous number of papers and patents dealing with the chemistry or biological activity of pyrazolopyrimidines have been reported. However this article appears to be the first survey of the chemistry and biological activity of this class of compounds. 

Inclusion of premiums is, of course, an important determinant of the results. In some countries, such as those in Europe, premiums were more common than in others. In the Australian study (Wynen and Edwards 1990), for example, very few farmers received premiums at the time of the first survey in the mid-1980s. In a later study, all farmers received premiums though the net farm returns were variable, being similar to those of conventional neighbours in one year and considerably lower in the next (Wynen 2001). Obviously, factors other than price premiums may be of greater significance in the total picture. 

As part of the process of developing this guidance, the Agency conducted several surveys of NDA submissions for ER drug products to find out the number of times that IVlVCs were developed. The first survey included NDA submissions from 1982-1992 and found 9 IVlVCs in 60 submissions. A more recent survey included NDA submissions from October 1994 to October 1995 and found 9 IVlVCs in 12 submissions. 

VVTinery quality control has not been formalized in the United States to the point where standard methods, practices, or performance criteria are established. The literature devotes little attention to the subject of wine production quality control, per se. The first survey of quality control in the California wine industry appeared as late as 1972 (I), and it is limited to sanitation aspects. One does not find chapters on quality control of winemaking in any of the major wine technology texts. 

As abundantly illustrated in the first survey, marine organisms produce and sequester an enormous number of organohalogens. It is estimated that more than 15,000 marine natural products of all types have been described (106). This author... 

The first survey of natural organohalogens documented 570 halogenated terpenes (1). The present update describes many additional new members of this important class of marine and terrestrial natural products. 

The halogenated acyclic marine monoterpenes are often considered to be the biogenetic precursors of the alicyclic monoterpenes that are presented in this section. Many of the preceding algae species also contain cyclic monoterpenes. As was the case in preceding sections only newly characterized compounds are numbered and the reader is referred to the first survey for structures of previously isolated compounds (7). 

Although the first survey listed 45 natural chlorinated sesquiterpene lactones, several such compounds were omitted in that coverage (1) and are described here. The novel sesquiterpene lactone chlorochrymorin (239) was isolated from Chrysanthemum morfolium (499), and the chlorohydrin graminichlorin (240) is found in Liatris graminifolia (500). The antibacterial AA-57 (241), which is related to pentalenolactone, is produced by a Streptomyces sp. (501). The plant Eupatorium chinense var. simplicifolium has yielded eupachifolin D (242) (502) (side-chain double bond stereochemistry revised (518)), and the new guaianolide andalucin (243) was characterized from Artemisia lanata (503). The previously known chlorohyssopifolins (1) have been studied for cytostatic activity, and the presence of one and even two chlorine atoms amplifies this activity (504). 

Nearly 40 halogenated eudesmanes and related halogenated sesquiterpenes were documented in the first survey (1), and terrestrial eudesmanes of all types are well represented with some 100 known examples (588). 

As was illustrated in the first survey, all known halogenated terrestrial diterpenes are chlorohydrins (1), and that continues to be mainly the case. Obviously, one must be alert to the possibility of artifact formation from ring opening of the corresponding epoxide during isolation. Many nonhalogenated terrestrial diterpenoids also continue to be isolated (622). 

Gorgonians produce the largest complement of chlorine-containing marine metabolites - more than 50 were illustrated in the first survey (7) - and many more nonchlorinated gorgonian diterpenes are known (665-667). There is evidence to indicate that these gorgonian diterpenoids are feeding deterrents to reef fishes. Gorgonian corals can achieve densities of up to 20 colonies per square meter on the reef (668, 669). 

Another prolific gorgonian is Junceella, and these animals contributed 15 chlorinated briarane diterpenoids to the first survey. A series of juncins A-F from the Red Sea Junceella juncea were presented earlier, although C and F were not... 

Several new halogenated bicyclic acetogenins of the laurefucin type have been discovered in marine organisms since the first survey (1). Thus, the Coral Sea red seaweed Dasyphila plumariodes contains the new isolaurefucin methyl ether (696) (789). Neoisoprelaurefucin (697) was characterized from a Japanese... 

This section and the section on alkaloids in the first survey (7) are artificially small since many halogenated alkaloids are presented in the sections on pyrroles, indoles, carbolines, tyrosines, and other nitrogen heterocycles. It might be noted that the very large number of brominated alkaloids that are obviously tyrosine-derived are now included in Sect. 3.22.3 (Tyrosines). 

Most of the known natural brominated pyrrole alkaloids are found in sponges, and several new examples were isolated since the first survey (1). Reviews are available that discuss the occurrence and syntheses of these metabolites (1236-1238). The Papua New Guinea sponge Agelas nakamurai has yielded the new simple pyrroles 1222 and 1223 (1239). The dibromo analog (1224) of 1223 along with enantiomeric lactams 1225/1226, which were separated by chiral HPLC, and... 

As illustrated in the first survey, marine bryozoans ( moss animals ) are preeminent practitioners of organic synthesis, particularly in the production of haloge-nated indoles. Thus, the North Sea bryozoan Securiflustra securifrons produces... 

While there are no newly reported naturally occurring benzodiazepines since the first survey (7 ). the interest in this area remains high. The current status of research and clinical implications has been reviewed (1484). It is noted that natural benzodiazepines, including seven known halogenated examples (1), are found in soil, plants, animal and human tissues, and are chemically identical to their pharmaceutical counterparts. The endogenous formation of benzodiazepines by plant cells (Artemisia dracunculus and Solarium tuberosum) has been demonstrated for delor-azepam, temazepam, and diazepam (1485). 

Although no new halogen-containing tetracyclines have been reported since the first survey (1), the gene responsible for the chlorination of tetracycline in Streptomyces aureofaciens (Fig. 3.24) has been cloned and the sequence of nucleotides determined (1651). The gene product is a 452 amino acid chlorination enzyme. 

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