Cinchona spp

Quinamine, CjgH240jN2. This alkaloid was isolated from Cinchona succiruhra bark by Hesse and subsequently found by him in the barks of several cinchona spp. but especially in C. ledgeriana bark. It has been examined in detail recently by Henry, Kirby and Shaw. )... 

Cinchona PelUtierana, alkaloids, 466 Cinchona spp., alkaloids, 418, 424 Cinchona, total alkaloids. See Totaquina. Cinchonamine, 419, 465 Cinchonhydrines, 440, 452 Cinchonicine (cinchotoxine), 410, 442, 451 Cinchonidine, 419, 427 constitution, 435 apoCinchonidlne, 448, 452 J3-Cinchonidine, 448, 452 Cinchonifine (dihydrocinchonine) 428 Cinchonine, 410, 421, 427, 583 constitution, 435 oxidation, 436 structural formula, 442 /leieroCinchonine (/i-cinchonine), 451 isoCinchonines, 451 Cinchoninic acid, 454 Cinchonino, 421 Cinchoninone, 437, 438, 442 Cinchotenidine, 436 Cinchotenine, 436... 

Cinchona alkaloids [Qninidine (6), Quinine (7)] Cinchona spp. (Cinchona bark) Cardiac antiarrhythmic Antimalarial... 

Quinidine (6) and quinine (7) are diastereomeric quinoline alkaloids obtained from Cinchona spp. Quinidine (6) is included in many pharmacopeias for its antiarrhythmic effects.Quinine was the first antimalarial drug and served as an effective remedy for this deadly infectious disease in colonial times, making European settlement in many tropical and subtropical parts of the world possible.Owing to the development of resistance to synthetic antimalarials, quinine is still reverted to some extent for this... 

Shikimic acid and quinic acid are useful synthons for the preparation of drugs (Chapter 15). Both are plant products shikimic acid from niicium spp. and quinic acid from Cinchona spp. Yields are quite low, however. Moreover, quinic acid is stored in the bark, the removal of which kills the plant. 

The availability of ctetq) advanced synthons that carry the required chirality is an advantage, particularly in projects aimed at industrial total synthesis. Natural products are often used as synthons, ideally fi om a renewable source, such as microbial fermentations. In a few cases, biotechnology has become an ahemative source. The total theses of the antitumor agent esperamicin A and the immunosuppressant FK-506 are exanq>les. In both cases, the synthon was quinic acid (Barco 1997), cheaply obtained by biotechnology (Chapter 14.1.e) rather than fi om the environmentally noxious extraction fi om the bark of Cinchona spp. Used to build up combinatorial libraries, quinic acid has gained further inq)ortance in organic thesis (Phoon 1999). 

Cinchona officinalis [bark], Cinchona spp., Remijia pedunculata (Rubiaceae) Quinine synthesized (1944) by Robert Burns Woodward (USA, Nobel Prize, 1965, Chemistry)... 

By the 1850s and 1860s quinine had reached its apex in the physician s armamentarium. Cinchona spp. were mentioned thirteen times among the primary list of substances in the United States Pharmacopoeia of 1850, twelve times in 1860, and thirteen times again in 1870.71 Cinchona spp. covered nearly fifty pages in the 1858 edition of the United States Dispensatory, and ten pages were spent discussing three different preparations of quinine.72 Never before or since were cinchona and quinine so prominently featured in the pharmaceutical compendia. 

Small quantities of alkaloid, not definitely located, occur in the seeds of Cinchona spp. (45,46), Strychnos quaqua Gilg. (44), Narcissus (1), Genista spp., and Ulex europaeus L. (47). The behavior upon germination varies to some extent depending upon the class concerned, but the general tendency is for alkaloids to appear or increase in amount in the growing tissues and, where present, to disappear in the passive ones. 

For malaria Artemisia annua or absinthium, Brucea javanica (fruit, root, or leaf), Uvaria spp. (any species, rootbark, stembark, or leaf), garlic vine Mansoa standleyi), or the bark of Cinchona spp. from which quinine was made can be used. Though malaria is resistant to quinine, it does not seem to have developed resistance to the more chemically complex Cinchona plant itself... 

As part of our studies on pharmaceutically important alkaloids in C. roseus and Cinchona spp. several aspects of their bios5mthesis were chciracterized and a number of enzymes were purified [4]. In the accumulation of alkaloids in suspension cultured C. roseus cells, it was found that the supply of isoprenoid precursors was a limiting factor. This prompted us to fiarther studies, thereby focusing on the early steps of the isoprenoid biosynthesis (fig. 2). Little was known of these enzymes from plants and except for HMG-CoA reductase, none of the enzymes was characterized [5,6]. Furthermore, there exists much controversy on the subcellular localization of this pathway [7,8]. 

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