Alkaloids, Cinchonidine,

The group of Terashima [35] developed an asymmetric domino Michael/aldol process using the chinchona alkaloid (-)-cinchonidine (2-103), to prepare an intermediate for the synthesis of the natural product (-)-huperzine A (2-102) [36] (Scheme 2.22). 

The enantioselective hydrogenation of prochiral substances bearing an activated group, such as an ester, an acid or an amide, is often an important step in the industrial synthesis of fine and pharmaceutical products. In addition to the hydrogenation of /5-ketoesters into optically pure products with Raney nickel modified by tartaric acid [117], the asymmetric reduction of a-ketoesters on heterogeneous platinum catalysts modified by cinchona alkaloids (cinchonidine and cinchonine) was reported for the first time by Orito and coworkers [118-121]. Asymmetric catalysis on solid surfaces remains a very important research area for a better mechanistic understanding of the interaction between the substrate, the modifier and the catalyst [122-125], although excellent results in terms of enantiomeric excesses (up to 97%) have been obtained in the reduction of ethyl pyruvate under optimum reaction conditions with these Pt/cinchona systems [126-128],... 

The other two cinchona alkaloids, cinchonidine and quinidine, are stereo-isomers of cinchonine and quinine. 

Platinum catalysts modified with members of the cinchona alkaloids are effective enantioselective catEilysts for the hydrogenation of a keto esters giving the chiral a hydroxy esters with ee s as high as 95%. >72 of the cinchona alkaloids, cinchonidine (30) and cinchonine (31) appear to be more effective than quinine (32) and quinidine (33). With cinchonidine the (R) lactate, 34, is... 

Conversely (Scheme 9), the threo aminoepoxides 96 and 97 were obtained from diphenylsulfoniumlepidylide (93) and iV-acetylmero-quinene aldehyde (55) (17). The ylide was formed from 4-methyl-sulfonylquinoline (91) and methylenediphenylsulfurane (92) and was treated with aldehyde 55 to give a mixture of the threo iV-acetyl epoxides 94 and 95. Removal of the. -acetyl group led to the aminoepoxides 96 and 97 which underwent intramolecular cyclization to give a mixture of the erythro alkaloids cinchonidine (98) and cinchonine (99). 

Another example worth mentioning is catalytic enantioselective hydrogenation of ketones. This reaction over non-chiral catalysts when a ketone contains a prochiral center produces racemic mixtures of optical isomers. The kinetics of 1 -phenyl-1,2-propanedione hydrogenation was studied in the presence of a chiral modifier -natural alkaloid cinchonidine (Figure 7.7)... 

The simplest cinchona alkaloids, cinchonidine and its 10,11-dihydro-derivative, have been shown by D-tracer studies and by NEXAFS and ATR-IR spectroscopy to adsorb by interaction of the quinoline moiety with the platinum surface. Mechanistic studies have established that a site exists adjacent to the open-3 conformation of adsorbed cinchonidine at which pyruvate ester can undergo selective enantioface adsorption. Hydrogenation of the preferred enantioface results in preferential formation of one enantiomer of the product, methyl lactate, MeC H(OH)COOMe. Pt modified by cinchonidine provides R-lactate preferentially, whereas the near enantiomer cinchonine provides 5-lactate in excess. Values of the enantiomeric excess of 75% can be obtained without optimisation, and of 98% under special conditions. In solution, conditions that achieve enantioselectivity normally promote the reaction rate by a factor of 2 to 100 depending on conditions. ... 

Table 5.4. The effect of the structure of modifier alkaloids, cinchonidine (Cnd) and cinchonine (Cn), on the enantioselective hydrogenation of ethyl pyruvate into ethyl lactate over 5% Pt-alumina.

Once the imprinting system has been devised to yield favorable monomer-template complexation and the necessary porosity, the preparation of monolithic polymer rods for HPLC is relatively simple. The general protocol detailed below uses an in situ polymerization method developed by Frechet and Svec [4]. This technique was used by Matsui in the preparation of MIP monolith rods for HPLC separation of antimalarial cinchona alkaloids, ( ) cinchonidine and (+) cinchonine, as well as the structural analogues quinidine and quinine [45]. 

The anti-rheumatic naproxen is also derived from 2-naphthol it is produced by the Friedel-Crafts acylation of 2-methoxynaphthalene and subsequent Willgerodt-Kindler reaction. Since only the S-configuration is effective, the racemic mixture is resolved with the alkaloid cinchonidine. 

Keywords Alkaloids quinidine cinchona alkaloids cinchonidine cinchonine quinine... 

An example is the asymmetric conjugate addition of a thiophenol to cyclohexenone to give (42) catalysed by the alkaloid cinchonidine. 

The naturally occurring cinchona alkaloids, cinchonidine, quinine, and quinidine, were hydroformylated selectively to the corresponding terminal aldehyde derivatives with 87, 71, and 85% isolated yields, respectively, using Rh(CO)2(acac)/tetrapho-sphite/5 catalyst system at 90 °C and 20bar CO H2 = 1 1 in toluene [15]. 

Nicotine boldine and other aporphine alkaloids C-toxiferine coniine and other piperidine alkaloids cytisine and other quinohzidine alkaloids epibatidine tubocurarine Berbamine, berberine, and other isoquinoline alkaloids cinchonidine and other quinoline alkaloids corynanthine, yohimbine, and other indole alkaloids emetine ephedrine ergometiine and related ergot alkaloids Ergocornine and related ergot alkaloids bulbocapnine and related aporphine alkaloids anisocycline, stylopine, and related protoberberine alkaloids salsolinol and related isoquinohnes BicuculUne, cryptopine, hydrastine, and related isoquinoline alkaloids securinine harmaline and related beta-carboline alkaloids Corymine, strychnine, and related indole alkaloids Histrionicotoxin and related piperidines ibogaine and related indole alkaloids nuciferine and related aporphine alkaloids... 

---