Quinine addition

Very recently, we (85) observed that in simple 1,2-additions quinine was again effective. Thus, when diethylzinc is added to a solution of benzaldehyde in toluene in the presence of catalytic amounts of quinine, (— )-phenylethyl-carbinol is formed in an e.e. of 72%. 

Additive effect these drugs prolong the Q-T interval. In addition, quinine inhibits CYP2D6-mediated metabolism of procainamide... 

Eight subjects took zidovudine for 3 days with and without probenecid 500 mg every 8 hours for 3 days, and then additional quinine sulfate 260 mg every 8 hours (47). Probenecid increased the AUC of zidovudine by 80%. Quinine prevented the probenecid effect but had no effect on zidovudine kinetics when it was taken without probenecid by four other subjects. All of the effects were secondary to changes in zidovudine metabolism, since neither probenecid nor quinine changed the renal ehmination of zidovudine. 

Ketene can also be added to trihalosubstituted aldehydes or ketones (12) to form 4-trihalomethyloxetanones. If this addition is performed in the presence of optically active bases such as quinine [130-95-0] chiral lactones are obtained (41,42). 

The following are amongst the reagents that have been reported as being added to the mobile phase acids for quinine alkaloids [184], ninhydnn for amino acids [185 — 187], fluorescamine for biogenic amines [188] Fluorescein sodium [189], dichlorofluorescein [190], rhodamine 6G [191], ANS reagent [192] and bromine [193] have all been descnbed as additives to mobile phases... 

The cinchona alkaloids of practical importance are quinine, quinidine, cinchonine and cinchonidine, but, in addition, over twenty others have been isolated from cinchona and cuprea species. Their names and formulae are as follows ... 

Numerous new salts and additive compounds of cinchona alkaloids, and especially of quinine, have been described, of which only a few can be mentioned as examples quinine additive compounds with sulph-anilamide, t quinine salts of (+) and (—)-pantothenic acid, °( > quinine sulphamate and disulphamate, °( organo-mercury compounds of quinine and cinchonine such as quinine-monomercuric chloride. Various salts and combinations of quinine have also been protected by patent, e.g., ascorbates and nicotinates. 

In the cases of quinine and quinidine there is an additional complication, except for reaction (c), owing to partial de-methylation of the methoxyl group, thus in the action of sulphuric acid on quinine there may be four products of formula E, viz., the two geometrical isomerides apoquinine and isoapoquinine (for which Q is 6-hydroxyquinolyl) and their methyl ethers, j8-isoquinine and a-isoquinine respectively (for which Q is 6-methoxyquinolyl). 

Chinchona alkaloids, such as quinine, are readily available quinuclidine chiral bases which have been used extensively in catalytic Michael additions239 243. Methy 1-2,3-dihydro-1-oxo-l/f-in-dene-2-carboxylate (1) is most frequently used as the Michael donor in these studies. Enantiose-lectivities as high as 76% are reached in the additions to 3-buten-2-one. Modest enantioselec-tivities (< 67%) were also obtained with ethyl 2-oxo-l-cyclohexanecarboxylate and methyl l,3-dihydto-3-oxo-l-isobcnzol urancarboxylate244 245. 

Many racemic mixtures can be separated by ordinary reverse phase columns by adding a suitable chiral reagent to the mobile phase. If the material is adsorbed strongly on the stationary phase then selectivity will reside in the stationary phase, if the reagent is predominantly in the mobile phase then the chiral selectivity will remain in the mobile phase. Examples of some suitable additives are camphor sulphonic acid (10) and quinine (11). Chiral selectivity can also be achieved by bonding chirally selective compounds to silica in much the same way as a reverse phase. A example of this type of chiral stationary phase is afforded by the cyclodextrins. 

Addition to alkenes of the form RCH=CH2 has been made enantioselective, and addition to RCH=CHR both diastereoselective enantioselective, by using optically active amines, such as 81,82 (derivatives of the naturally occurring quinine... 

Figure 27 shows potential oscillation in the presence of quinine hydrochloride and sucrose as a mixture [21]. The mean value of low potentials of the initial five pulses was taken as b,sds- In the presence of ImM quinine hydrochloride without sucrose, in contrast to oscillation without any substance in phase wl, iiB,sDS was more positive by 56 mV and E and a,sds> slightly more negative. This change was due only to quinine hydrochloride. With sucrose in addition to quinine hydrochloride, iiB,sDS shifted to more negative values. With 1 mM quinine hydrochloride and 500 mM sucrose, the oscillation mode was basically the same as with only 500 mM sucrose. 

Taking Tomioka s pioneering work [8] as a precedent, we have screened 13-amino alcohols as chiral modifiers [9] in the nucleophilic addition of lithium 2-pyridinylacetylide 6 to the pMB protected ketimine 5. We were pleased to discover that when 5 was treated with a mixture prepared from 1.07 equiv each of quinine and 2-ethynylpyridine by addition of 2.13 equiv of n-BuLi in THF at -40 to -20 °C, the desired adduct 19 was obtained in 84% yield with maximum 64% ee. Soon after, we found selection of the nitrogen protective group had great influence on the outcome of the asymmetric addition and the ANM (9-anthranylmethyl)... 

Interestingly, Jacobsen et al. have also reported that addition of a /3-hydroxy ammonium salt to the reaction medium accelerates the isomerization in the presence of an /V-benzylated quinine salt epoxidation of cw-stilbene with (27) gives Zrarax-stilbene oxide with 90% ee as the major product (trans cis= >96 4).109 In 2000, Adam et al. reported that the isomerization ratio was related to the triplet-quintet energy gap of the radical intermediate which was affected by the... 

A complex naturally occurring amino acid 5-hydroxypiperazic acid (5HyPip) 100 was prepared by a multistep procedure that included Diels-Alder addition of 2,4-pentadienoic acid to phthalazinedione 83a as a first step (Scheme 24). Adduct 97 was esterified and oxidized with mercuric acetate to 98, which on hydrogenation over rhodium on alumina and subsequent hydrolysis provided a mixture of enantiomers from which the required enantiomer 99 was obtained by resolution with quinine. Its hydrazinolysis provided 100 [71JCS(C)514 77H119],... 

Wynberg3 has also effected stereoselective addition of (C2H5)2Zn to aryl aldehydes using cinchona alkaloids, particularly quinine and quinidine, which result in (R)- and (S)-alcohols in excess, respectively. The highest enantiomeric excess, 92% ee, was observed with o-ethoxybenzaldehyde catalyzed by quinine. 

In addition to the spectrophotometric method discussed in section 12.1.1.1 Aznarez et al. [2] have described a method based on the molecular fluorescence of boron with dibenzoylmethane. The preliminary soil digestion and extraction procedures are identical to those described earlier. The reactive fluorescence intensity of the boron complex is measured at 400nm with excitation at 390nm and quinine sulphate as reference. 

More than half of the reported secondary metabolites from macroalgae are isoprenoids. Terpenes, steroids, carotenoids, prenylated quinines, and hydroqui-nones make up the isoprenoid class, which is understood to derive from either the classical mevalonate pathway, or the mevalonate-independent pathway (Stratmann et al. 1992). Melavonic acid (MVA) (Fig. 1.2) is the first committed metabolite of the terpene pathway. Dimethylallyl (dl meth al lal) pyrophosphate (DMAPP) (Fig. 1.3) and its isomer isopentenyl pyrophosphate (IPP, Fig. 1.3) are intermediates of the MVA pathway and exist in nearly all life forms (Humphrey and Beale 2006). Geranyl (ja ran al) (C10) and famesyl (C15) units are generated by head-to-tail (Fig. 1.3) condensation of two (for C10) or three (for C15) 5-carbon DMA-like isoprene units, identifiable in final products by the characteristic fish-tail repeating units, as traced over the structure of a sesquiterpene in Fig. 1.3 (Humphrey and Beale 2006). Additional IPP condensation with famesyl pyrophosphate (FPP)... 

Quinine and quinidine, as well as cinchonidine and cinchonine, are diastereo-meric pairs. However, at the critical sites—the P-hydroxyamine portions of the molecules—they are enantiomeric. Thus if quinine is used as the chiral catalyst in an asymmetric transformation (i.e., with one enantiomer being formed in excess), the other enantiomer is formed in excess when quinidine is used. Table 2 gives a representative example, the thiol addition reaction (19). 

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