Cinchona structure

Functionalization of the cinchona structure with a thiourea at the C6 position of the quinolone ring was demonstrated shortly after development of the C9 derivatives [69]. The transformation of the C6 methoxy group into a thiourea bearing a 3,5-di(trifluoromethyl)phenyl group, without affecting the stereochemistry at C9, resulted in a highly effective organocatalyst for the asymmetric Henry reaction of nitromethane with aromatic aldehydes (Scheme 6.28). 

A catalytic enantio- and diastereoselective dihydroxylation procedure without the assistance of a directing functional group (like the allylic alcohol group in the Sharpless epox-idation) has also been developed by K.B. Sharpless (E.N. Jacobsen, 1988 H.-L. Kwong, 1990 B.M. Kim, 1990 H. Waldmann, 1992). It uses osmium tetroxide as a catalytic oxidant (as little as 20 ppm to date) and two readily available cinchona alkaloid diastereomeis, namely the 4-chlorobenzoate esters or bulky aryl ethers of dihydroquinine and dihydroquinidine (cf. p. 290% as stereosteering reagents (structures of the Os complexes see R.M. Pearlstein, 1990). The transformation lacks the high asymmetric inductions of the Sharpless epoxidation, but it is broadly applicable and insensitive to air and water. Further improvements are to be expected. 

It has already been shown that both the laevorotatory and dextrorotatory cinchona alkaloids on degradation yield scission products from the quinuclidine nucleus, which are structurally and optically identical, for example, meroquinenine, [a] -f- 27 6° d-/3-cincholoiponic acid. 

There are a number of other synthetic substances analogous with or approximating to the cinchona alkaloid structure which it is more convenient to deal with in discussing the correlation of chemical structure with pharmacological action in this group (p. 469). 

Chondrodendron polyanthum, 371 Chondrodendron tomentosum, 363, 371, 373, 377, 391 alkaloids, 376 Chondrodine, 363, 364 Chondrofoline, 364, 365 Chrycentrine, 172, 313 Chiysanthemine, 773 Chrysanthemum cineraricefoHum, 773 Chuchuara, 781 Chuehuhuasha, 781 Cicuta virosa, 13 Cinchamidine, 419, 429 Cinchene, 439 Cinchenine, 438, 439, 440 apoCinchenine, 440, 441 Cincholoipon, 438 Cincholoiponic acid, 438, 443 Cinchomeronic acid, 183 Cinchona alkaloid structure, synthesis, 457 Cinchona alkaloids, bactericidal action of some derivatives, 478 centres of asymmetry, 445 constitution, 435 formulae and characters of transformation products, 449, 451 general formula, 443 hydroxydihydro-bases, 448, 452-4 melting-points and specific rotations, 446... 

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... 

The molecular modelling approach, taking into account the pyruvate—cinchona alkaloid interaction and the steric constraints imposed by the adsorption on the platinum surface, leads to a reasonable explanation for the enantio-differentiation of this system. Although the prediction of the complex formed between the methyl pyruvate and the cinchona modifiers have been made for an ideal case (solvent effects and a quantum description of the interaction with the platinum surface atoms were not considered), this approach proved to be very helpful in the search of new modifiers. The search strategy, which included a systematic reduction of the cinchona alkaloid structure to the essential functional parts and validation of the steric constraints imposed to the interaction complex between modifier and methyl pyruvate by means of molecular modelling, indicated that simple chiral aminoalcohols should be promising substitutes for cinchona alkaloid modifiers. Using the Sharpless symmetric dihydroxylation as a key step, a series of enantiomerically pure 2-hydroxy-2-aryl-ethylamines... 

Not so long ago, the general opinion was that high enantioselectivity can only be achieved with natural, structurally unique, complex modifiers as the cinchona alkaloids. Our results obtained with simple chiral aminoalcohols and amines demonstrate the contrary. With enantiomeric excesses exceeding 80%, commercially available naphthylethylamine is the most effective chiral modifier for low-pressure hydrogenation of ethyl pyruvate reported to... 

Since the initial work of Onto et al. (1) a considerable amount of work has been performed to improve our understanding of the enantioselective hydrogenation of activated ketones over cinchona-modified Pt/Al203 (2, 3). Moderate to low dispersed Pt on alumina catalysts have been described as the catalysts of choice and pre-reducing them in hydrogen at 300-400°C typically improves their performance (3, 4). Recent studies have questioned the need for moderate to low dispersed Pt, since colloidal catalysts with Pt crystal sizes of <2 nm have also been found to be effective (3). A key role is ascribed to the effects of the catalyst support structure and the presence of reducible residues on the catalytic surface. Support structures that avoid mass transfer limitations and the removal of reducible residues obviously improve the catalyst performance. This work shows that creating a catalyst on an open porous support without a large concentration of reducible residues on the Pt surface not only leads to enhanced activity and ee, but also reduces the need for the pretreatment step. One factor... 

Indicate the structural elements that are crucial for the functioning of the cinchona alkaloids as chiral modifiers. 

The structures of quinine, cinchonidine, quinidine, and cinchonine are shown in Figure 3. Other workers (16,17) have discussed these alkaloids and their use as catalysts in some detail. An excellent discussion of cinchona-alkaloid-catalyzed reactions prior to 1968 was given by Pracejus (18). In this section we discuss only four aspects of these reactions. 

The overall steric demands of the catalyst and the substrate are important in the spatial arrangement of the H-bonded complex. Consequently, although the less rigid ephedrinium salts have been used with some success, they are generally less effective than the derivatives of the cinchona alkaloids, the rigidity of which imposes a greater stereochemical restraint on the structure of the H-bonded complexes. 

The catalyst is a combination of a chemo-catalyst and a natural product taken from the cinchona alkaloids giving amazing results. In phosphine catalysed asymmetric catalysis these types of structures are lacking, as nature does not produce phosphines ( ) and the phosphines used in the early years of development of asymmetric homogeneous catalysis lacked the complexity of... 

Figure 14.15. Structures of some alkaloids from Cinchona bark...

FIGURE 1.2 Structure and stereochemistry of commercially available cinchona alkaloid CSPs, marketed under trade name CHIRALPAK by chiral technologies europe. QN denotes quinine- and QD quinidine-derived and AX refers to their anion-exchanger capabilities vide infra). 

Since the last major review of the biosynthesis of the monoterpenoid indole alkaloids (97), there have been several full and partial 98-104) reviews of various aspects of the work that has been conducted since 1974. Two major developments have dominated the field in this period, namely, the demonstrations that (i) strictosidine (33) is the universal precursor of the monoterpenoid indole alkaloids and (ii) selected cell-free systems of C. roseus have the ability to produce the full range of alkaloid structure types, including the bisindoles. This section traces some aspects of these developments, paying particular attention to work been carried out with C. roseus, and omitting work, important though it may be, on other monoterpenoid indole alkaloid-producing plants, e.g., Rauwolfia, Campto-theca, and Cinchona. 

The advent of chiral Brpnsted base catalysis began with the recognition that the Cinchona alkaloids serve as excellent catalysts [7-12] and privileged structures... 

This group of alkaloids has two structurally different a. The a of alkaloids found in the genus Cinchona (Ruhiaceae), such as quinine, quinidine, cinchonidine and cinchonine, is L-tryptophan. The j8 is tryptamine and the

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