Quinidine structure

Log P calculation for quinidine with the atom contribution method according to Ghose and Crippen. R group connected to C X heteroatom = double bond aromatic bond aromatic single bond (e.g. C=N in pyrrole) subscripts give the hybridization state and superscripts the formal oxidization number. For the quinidine structure see Fig. 14.1. 

These results indicate that quinine and quinidine differ in structure from cinchonine and cinehonidine in containing a methoxyl group in position 6 in a quinoline nucleus. The identity of the other oxidation products, meroquinenine, cincboloiponic and loiponic acids, in all foiu" cases indicates that the second half of the molecule has the same structure in all four alkaloids. Further, this second half must be joined to the quinoline nucleus at position 4 by a group capable of conversion into carboxyl. 

The directions of rotation at C and C have been arrived at from the following considerations. The deoxy-bases (II p. 443 Q = quinoline residue) obtained from cinchonine and cinchonidine are structurally identical, i but optically different, and since they must be optically identical at C and C, and C is no longer asymmetric, the difference between them (see table, p. 446) must be due to difference in direction of rotation at C , which must therefore be dextrorotatory in cinchonine and laevorotatory in cinchonidine, and this must also be true of quinidine and quinine respectively and of the corresponding dihydro-bases. The keto-bases, cinchoninone and quininone, might be expected to exist each in two pairs, since carbon atom 8 is, according to the formula (p. 442), asymmetric, but it is better represented by the tautomeric grouping —... 

FIGURE 4.14 Structure of the CYP2D6 competitive inhibitor, quinidine. 

Figure 3. Structures of quinine, cinchonidine, quinidine, and cinchonine.

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. 

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). 

FIGURE 1.19 X-ray crystal structures of selector-selectand complexes (ion-pairs) (a) O-9-(P-chloro-fert-butylcarbamoyl)quinine with iV-(3,5-dinitrobenzoyl)-(5)-leucine, (b) tbe pseudoenantiomeric complex of 0-9-( 3-cbloro-tert-butylcarbamoyl)quinidine with N-(3,5-dinitrobenzoyl)-(i )-leucine, (c) 0-9-( 3-cbloro-terf-butylcarbamoyl)quinine with N-(3,5-dinitrobenzoyl)-(5)-alanyl-(5)-alanine, and (d) comparison of tbe complexes of (a) and (c). Most hydrogens have been omitted for the purpose of clarity. (Reprinted from C. Czerwenka et al., Anal. Chem., 74 5658 (2002). With permission.)... 

Another issue is validated by the presented X-ray structures This is related to the pseudoenantiomeric character of the tert-butylcarbamates of quinine and quinidine (Figure 1.19a,b). Except for the vinyl on the backside of the quinuclidine ring, both the complexes that are actually diastereomeric to each other actually look like mirror images with regard to conformations and intermolecular interactions as well so that the pseudoenantiomeric experimental chromatographic behavior for DNB-Leu can be rationalized also on the basis of their X-ray crystal structures. 

This structural group of indole alkaloids covers simple indole alkaloids (e.g., tryptamine, serotonin, psilocin and psilocybin), /3-carboline alkaloids (e.g., harmine), terpenoid indole (e.g., ajmalicine, catharanthine and tabersonine), quinoline alkaloids (e.g., quinine, quinidine and cinchonidine), pyrroloindole... 

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

[Pg.114]

C9-epi-122 98% conv. (99% ee) after 30h, respectively (Figure 6.40). This structure-efficiency relationship supported the results already published by the Soos group for quinine- and quinidine-derived thioureas (Figure 6.39) [278]. C9-epimeric catalysts were found to be remarkably more efficient in terms of rate acceleration and stereoinduction than the analogs of natural cinchona alkaloid stereochemistry. This trend was also observed for the corresponding (thio)ureas derived from DHQD as shown by the experimental results in Figure 6.40 [279]. 

Propafenone has some structural similarities to propranolol and possesses weak 3-blocking activity. Its spectrum of action is very similar to that of quinidine, but it does not prolong the action potential. Its sodium channel-blocking kinetics are similar to that of flecainide. Propafenone is metabolized in the liver, with an average half-life of 5-7 hours. The usual daily dosage of propafenone is 450-900 mg in three divided doses. The drug is used primarily for supraventricular arrhythmias. The most common adverse effects are a metallic taste and constipation arrhythmia exacerbation can also occur. 

In the presence of a cinchona alkaloid, certain cyclic carboxylic anhydrides with meso structures are converted to the chiral diacid monoesters in up to 76% ee (Scheme 10) 31). Quinine or cinchonidine and quinidine or cinchonine show opposite asymmetric induction. 

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