Hydroquinidine

Mono-, di-, and trisubstituted olefins undergo osmium-catalyzed enantioselective dihydroxylation in the presence of the (R)-proline-substituted hydroquinidine 3.9 to give diols in 67-95% yields and in 78-99% ee.75 Using potassium osmate(VI) as the catalyst and potassium carbonate as the base in a tm-butanol/water mixture as the solvent, olefins are dihydroxylated stereo- and enantioselectively in the presence of 3.9 and potassium ferricyanide with sodium chlorite as the stoichiometric oxidant the yields and enantiomeric excesses of the... 

Studies of the transfer of Br+ and I+ from amine-coordinated halonium ions to acceptor l-co-alkenols have been undertaken to determine the mechanism in an effort to assist in the development of chiral transfer reagents. Transfer of Br+ and I+ from two commercially available dimeric hydroquinine and hydroquinidine ligands ((DHQ)2PHAL and (DHQD)2PHAL) to various 1, (o-alkenols and l,co-alkenoic acids is shown to provide enantiomeric excesses of 4-47% depending on the acceptor alkene. 

An elecrophilic Br+ or I+ can be successfully transferred to hydroquinidine (13) and two of its commercially available derivatives (4-chlorobenzoate and 9-phenanthryl ether hydroquinidines) simply by mixing two equivalents of the hydroquinidine with one equivalent of sym(co d ne)2-X+ perchlorate in methylene chloride or acetonitrile. H NMR studies (31) showed that the iodonium ion was associated with the nitrogen at the quinuclidine portion of the hydroquinidine instead of the aromatic nitrogen and also that all of the sym-collidines were removed from the X+ since only free collidine and no collidine-I+ peaks were observed. The (hydroquinidine)2-halonium ion is stable in solution for more than 30 minutes at room temperature these ions (and their parent amines) are more soluble in methylene chloride than in acetonitrile, and having R group other than hydrogen also improves the solubility. 

The hydroquinidine and hydroquinine dimers (DHQD)2PHAL (14), (DHQ)2PHAL (15) and (DHQD)2Pyr (16) are commercially available metal... 

Table 3. Enantiomeric excesses obtained from halocyclizations of various l,o-alkenols or l,co-alkenoic acids with halonium ions of dimeric hydroquinidine or dimeric hydroquinine species 14,15,16. ... 

A given sample containing a mixture of quinidine (I) and hydroquinidine (II) is dissolved in requisite quantity of deutrochloroform (CDC13) along with 2, 3, 5-triboromothiophene as the internal standard. The quantitative determination is carried out by comparing the peak area attributed by ethylene of (I) at 5.16 ppm to the internal standard peak at 6.93 ppm. The coefficient of variation was found to be 1%. 

Figure 1.8 Use of capillary electrophoresis for separating the diastereomers quinine (QN) and quinidine (QD) (H-QN is hydroquinine, QD-N-OX is quinidine iV-oxide, H-QD is hydroquinidine, 3-OH-QD is 3-hydroxyquinidine, and asterisk is an unidentified impurity). Reprinted from [17], copyright 2001, with permission from Elsevier. (Capillary 47 cm X 75 pm i.d. (40 cm to detector) (Polymicro Technologies) running buffer 50 mM phosphoric acid containing 15 mM /3-cyclodextrin adjusted to pH 2.5 with NaOH voltage 7 kV current 21 pA injection at 0.5 psi for 4 s detector fluorescence (HeCd laser) excitation 325 nm, emission 450 nm.)...

Chiral sulfoxides have emerged as versatile building blocks and chiral auxiliaries in the asymmetric synthesis of pharmaceutical products. The asymmetric oxidation of prochiral sulfides with chiral metal complexes has become one of the most effective routes to obtain these chiral sulfoxides.We have recently developed a new heterogeneous catalytic system (WO3-30% H2O2) which efficiently catalyzes both the asymmetric oxidation of a variety of thioethers (1) and the kinetic resolution of racemic sulfoxides (3), when used in the presence of cinchona alkaloids such as hydroquinidine 2,5-diphenyl-4,6-pyrimidinediyl diether [(DHQD)2-PYR], Optically active sulfoxides (2) are produced in high yields and with good enantioselectivities (Figure 9.3). ... 

Table 9.4 presents results of different sulfides that underwent asymmetric oxidation using catalytic WO3 in the presence of cinchona alkaloids such as hydroquinidine 2,5-diphenyl-4,6-pyrimidinediyl diether [(DHQD)2-PYR] with 30 % H2O2 as oxidant. 

Leaves of Cinchona succirubra Pav. from a trial plantation in the north of Thailand have been reported to contain the typical bases of quinoline alkaloids (cinchonine, cinchonidine, quinidine, quinine, di-hydroquinidine, and dihydroquinine) together with the indole bases quina-mine and 3-epiquinamine (97,98). 10-Methoxycinchonamine (92) has also been isolated from this plant for the first time. Except for the inclusion of alkaloid 92, the alkaloid pattern in C. succirubra is the same as that in the cross-species C. succirubra x C. ledgeriana from Guatemala. 

Ludwig E, Schmid J, Beschke K, et al. Activation of human cytochrome P-450 3A4-catalyzed meloxicam S -methylhydroxylation by quinidine and hydroquinidine in vitro. J Pharmacol Exp Ther 1999 290 1-8. 

As with some other quinolones, moxifloxadn also prolongs the QTC interval [265], although the prolongation time of 4—6 ms (i.e., 1.4—1.6% of the starting interval) is relatively minimal. For safety reasons, the treatment of patients with QT interval prolongation and certain cardiac diseases is therefore contraindicated. Other medicaments with a potential for prolonging the QT interval may not be administered simultaneously with moxifloxacin. These indude anti-arrhythmic drugs of class IA (e.g., quinidine, hydroquinidine, disopyramide) and III (e.g., amiodarone, sotalol, dofetilide, ibutilide), intravenous erythromydn, tricyclic anti-depressives, and cisapride etc. 

Dihydroquinidine 9-0-(9 -phenanthryl) ether4 (Aldrich, Cat. No. 38195-0 Hydroquinidine 9-phenanthryl ether) gave the highest enantioselectivity compared with several other commercially available dihydroquinidine derivatives 34% ee with dihydroquinidine 4-chlorobenzoate (Aldrich, Cat. No. 33648-3 Hydroquinidine 4-chlorobenzoate) and 61% ee with dihydroquinidine-9-0-(4 -methyl-2 -quinolyl) ether (Aldrich, Cat. No. 38194-2 Hydroquinidine 4-methyl-2-quinolyl ether). The submitters report that the reaction can be run on 0.5-mol scale using this procedure to afford comparable yields and enantiomeric purity of the diol product. 

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