Cupreine alkaloids

Like other alkaloids of this group, quinine forms molecular compounds with a variety of organic substances. With benzene and toluene it produces compounds of the formulae B. CgHg and B. C,Hg respectively, with phenol it gives the crystalline product B. CgHjOH, and similar combinations with polyhydric phenols, ethers, aldehydes and ketones are known. One of the most characteristic of these substances is cupreine-quinine, a combination of the two alkaloids, obtainable from cuprea bark, and at first regarded as a new alkaloid, and named homoquinine. ... 

Hydrocupreine (Dihydrocupreine), CigH2402N2. This alkaloid does not occur naturally, but can be produced by demethylating dihydroquinine or reducing cupreine. It crystallises from dilute alcohol in minute needles or from a mixture of chloroform and benzene in warty masses, m.p. 230° (dec.) with some sintering at 185-200°, is readily soluble in chloroform, alcohol or hot benzene, and much less so in ethyl acetate, insoluble in light petroleum, — 155-5° (G. and Wi ° 148-7°... 

Cupreines and cupreidines are pseudoenantiomers of Cinchona alkaloids with the replacement of quinoline C(6 )-OCH3 with an OH-group. The result is availability of an additional hydrogen-bonding moiety. 

To obtain these products selenium dioxide is allowed to react with the hydrogenated cinchona alkaloids or their derivatives in the presence of concentrated sulphuric acid and the products obtained are diluted with water and boiled. Selenohydroquinine is prepared from hydro-quinine sulphate or hydroquinine sulphuric ester, and forms yellow needles which remain unchanged below 235° C. selenoethylhydro-cupreine forms yellow needles, 5l.pt. 233° to 23-1° C., and selenohydro-cupreine separates as small, orange-coloured needles, w hich are unmelted below 235° C. The products are of use therapeutically. 

Cupreine. (hydroxycinchonine). C19H2202N2 2H20. One of the cinchona alkaloids. 

Figure 13.2 Structural features of cinchona alkaloid molecules (QN, quinine QD, quinidine CN, cinchonine CD, cinchonidine CPN, cupreine CPD, cupreidine).

This methodology, which can also be applied to acyclic a-substituted cyanoacetates, cyanothioacetates, and cyanoketones as nucleophiles, as well as acrylonitrile as Michael acceptor by using cupreine 171, quinine 170, and their respective pseudoenantiomers as catalysts, has been successfully employed in the enenatioselec-tive synthesis of an intermediate of the bromopyrrole alkaloid (-)-manzacidin A (Scheme 2.95) [264a]. 

Yuan and coworkers have reported an enantioselective three-component domino Knoevenagel/Michael/cyclization sequence using 226, a 1,3-dicarbonyl compound 228, and malononitrile 227 catalyzed by cinchona alkaloid cupreine 229 (Scheme 6.32). The spirocychc oxindole pyrans 231 were obtained in high yields (85-99%) and enantioselectivi-ties (up to 96% ee) [63]. Inconveniently, the reaction requires high dilutions (0.1-0.005 M) resulting in a large amount of used solvents. Macaev and coworkers have used chiral catalyst (-)-(S)-brevicolline 230 for the obtainment of the same... 

Cooperative catalysis using cinchona alkaloid derivatives in combination with metals such as silver have also been widely developed. On the basis of this concept, Escolano et al. have disclosed an enantioselective domino Michael-cyclisation reaction. This formal [3 + 2] cycloaddition occurred between isocyanoacetates and enones in the presence of a combination of a chiral hifunctional cinchona alkaloid, such as cupreine, and AgNOs to provide the corresponding chiral 2,3-dihydropyrroles in low to high yields and... 

Figure 6.1 Structures of the natural cinchona alkaloids and of cupreine and cupreidine. The analogs of quinine, quinidine, cinchonidine, and cinchonine with an ethyl at C3 (the dihydro species) are also isolated from natural sources.

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