Calcium chiral

As stated before, the enantioselective MBH reaction of cyclopent-2-en-l-one with 3-phenyl-1-propanal resulted in low enantioselectivities (<10%) when using (i )-BINOL and tributylphosphine. However, better results have been achieved using calcium chiral catalyst 379 along with BU3P, with the desired adduct provided in 56% enantiomeric purity (Scheme 2.215). ... 

H. Fujimoto, I. Nishino, K. Ueno and T. Umeda, Determination of the enantiomers of a new 1,4-dihydropyridine calcium antagonist in dog plasma achiral / chiral coupled high performance liquid cliromatography with electrochemical detection , 7. Pharm. Sci. 82 319-322(1993). 

A precursor in the synthesis of a promising calcium sensitizing agent from E. Merck [33], a chiral thiadiazin-2-one EMD 53986, 3,6-Dihydro-5-[l,2,3,4-tetrahy-dro-6-quinolyl]-6-methyl-2H-l,3,4-thiadiazin-2-one [26]. The study was performed using Celluspher , a CSP prepared from cellulose tri(p-methylbenzoate) according to a patent from Ciba-Geigy [34]. The spherical particles had a mean particle diameter of 20 3 pm and the mobile phase was pure methanol. 

Biocatalysis has emerged as an important tool for the enantioselective synthesis of chiral pharmaceutical intermediates and several review articles have been published in recent years [133-137]. For example, quinuclidinol is a common pharmacophore of neuromodulators acting on muscarinic receptors (Figure 6.50). (JJ)-Quinudidin-3-ol was prepared via Aspergillus melleus protease-mediated enantioselective hydrolysis of the racemic butyrate [54,138]. Calcium hydroxide served as a scavenger of butyric acid to prevent enzyme inhibition and the unwanted (R) enantiomer was racemized over Raney Co under hydrogen for recycling. 

The reagent can be used, for example, on silica gel, kieselguhr and Si 50000 layers as well as on aluminium oxide, cellulose or chiral layers. Neither do difficulties occur on RP 18, Diol, NHj and CN phases. Silver nitrate- [4] and calcium oxalate-impregnated layers [9] are also suitable. However, polyamide phases are colored yellow. 

D-Pantolactone and L-pantolactone are used as chiral intermediates in chemical synthesis, whereas pantoic acid is used as a vitamin B2 complex. All can be obtained from racemic mixtures by consecutive enzymatic hydrolysis and extraction. Subsequently, the desired hydrolysed enantiomer is lactonized, extracted and crystallized (Figure 4.6). The nondesired enantiomer is reracemized and recycled into the plug-flow reactor [33,34]. Herewith, a conversion of 90-95% is reached, meaning that the resolution of racemic mixtures is an alternative to a possible chiral synthesis. The applied y-lactonase from Fusarium oxysporum in the form of resting whole cells immobilized in calcium alginate beads retains more than 90% of its initial activity even after 180 days of continuous use. The biotransformation yielding D-pantolactone in a fixed-bed reactor skips several steps here that are necessary in the chemical resolution. Hence, the illustrated process carried out by Fuji Chemical Industries Co., Ltd is an elegant way for resolution of racemic mixtures. 

The reduction of quinazolinone 242 with hydrogen at 3 atm in the presence of a palladium-on-calcium-carbonate catalyst furnished perhydroquin-azolinone 243. The stereochemistry of 243, with four chiral centers, was not investigated (70M1767). 

A metal-nucleotide complex that exhibits low rates of ligand exchange as a result of substituting higher oxidation state metal ions with ionic radii nearly equal to the naturally bound metal ion. Such compounds can be prepared with chromium(III), cobalt(III), and rhodi-um(III) in place of magnesium or calcium ion. Because these exchange-inert complexes can be resolved into their various optically active isomers, they have proven to be powerful mechanistic probes, particularly for kinases, NTPases, and nucleotidyl transferases. In the case of Cr(III) coordination complexes with the two phosphates of ATP or ADP, the second phosphate becomes chiral, and the screw sense must be specified to describe the three-dimensional configuration of atoms. 

Extensive stmcture activity relationship (SAR) studies in this series revealed that unsymmetrical substitution on the heterocyclic ring and hence the introduction of chirality on the central carbon atom led to increased potency. Such asymmetrical dihydro-pyridines can be prepared by stepwise variation of the Hantzsch synthesis, based on the hypothetical alternate route to nifedipine. Thus, aldol condensation of methyl acetoacetate with 2,3-dichlorobenzaldehyde (13-1) gives the cinnamyl ketone (13-2). Reaction of that with the enamine (13-3) from ethyl acetoacetate gives the calcium channel blocker felodipine (13-4) [14]. 

S. Goldmann and J. Stoltefuss, 1,4-Dihydro-pyridines effect of chirality and conformation on the calcium-antagonistic and -agonistic effects, Angew. Chem. 1991, 103, 1587-605 Angew. Chem. Int. Ed. En. 1991, 30, 1559-1578. 

The relative concentration of dicarboxylic acids with respect to aminoacids is higher (by one or two orders of magnitude). As in the case of monocarboxylic acids, every possible isomer seemed to be present, ranging from C2 to C5 molecules. In the case of chiral molecules, the two enantiomers coexisted in nearly equal concentration. Oxalic acid was detected as calcium salt, but the state of the other dicarboxylic acids in the Murchison meteorite remains an open problem 24 >. Dicarboxylic acids, as monocarboxylic acids, seem to be the result of synthetic pathways that give mixtures at random 44-45... 

Figure 18 Synthesis of chiral synthon for calcium channel blocker (A) microbial reduction of 4,5-dihydro-4-(4-methoxyphenyl)-6-(trifluoromethyl)-lH-benzazepin-2,3-dione (56) (B) synthesis of chiral synthon for calcium channel blocker, dilthiazem enantioselec-tive enzymatic hydrolysis of racemic (57).

R de Souza Pereira. Comparison of biochemical effects produced by calcium ions and by monomers of polyacrylamide (acrylamide and bisacrylamide) on strains of Saccharomyces cerevisiae used for production of chiral synthons. Mol Cell Biochem 178 33-40, 1998. 

Chromatography on silica gel yielded 13.2 g racemate of lactone - trans-(+/-)-5-(4-fluorophenyl)-2-(l-methylethyl)-N,4-di-diphenyl-l-[2-(tetrahydro-4-hydroxy-6-oxo-2FI-pyran-2-yl)ethyl]-lFI-pyrrole-3-carboxamide. This racemate was divided by chiral synthesis which was made analogously the method in US Pat. No. 4,581,893. Then each isomer was saponificated with NaOFI and purificated by FIPLC. The calcium salt corresponding acid was prepared by reaction with 1 eq. of CaCl2-2Fi20 in water. 

In this approach (17), the prochiral fragment was attached to the auxiliary at only one point making the acid-catalysed release after transformation a simple procedure. Chirality was induced by the borohydride reduction of a carbonyl group on the pro-chiral fragment in the asymmetric environment created by complexation of calcium ions between the Cl and C2 oxygens of the hexose. The diastereomeric purity was good (-70%) but separation of the diastereomers was more problematic. 

D-Pantothenic acid is also traditionally produced by chemical processes which involve efficient but troublesome and costly crystallization of diastereomeric salts of pantoate and chiral amines. After lactonization of the isolated D-pantoate, d-pantolactone is reacted with / -alanine to give D-pantothenate. Because the monovalent salts of pantothenic acid are highly hygroscopic, conversion into the calcium salt is essential for convenient formulation. The third class of synthetic processes for optically active compounds makes use of biotechnology. For natural com-... 

Determine the priority order of the groups at position 4 of the 1,4-dihydro-pyridine ring in the calcium antagonist amlo dipine and state whether the compound is chiral. 

Five chiral calcium antagonists (including nimodipine) were separated using p-cyclodextrin as the stationary phase in a Merck Chiradex column (25 cm x 4.6 mm i.d.) with 0.1% triethylamine containing 5-100% of... 

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