Enantiomers, stereospecific synthesis

Sulfoxides without amino or carboxyl groups have also been resolved. Compound 3 was separated into enantiomers via salt formation between the phosphonic acid group and quinine . Separation of these diastereomeric salts was achieved by fractional crystallization from acetone. Upon passage through an acidic ion exchange column, each salt was converted to the free acid 3. Finally, the tetra-ammonium salt of each enantiomer of 3 was methylated with methyl iodide to give sulfoxide 4. The levorotatory enantiomer was shown to be completely optically pure by the use of chiral shift reagents and by comparison with a sample prepared by stereospecific synthesis (see Section II.B.l). The dextrorotatory enantiomer was found to be 70% optically pure. 

Syntheses of naphthyridone derivatives follow the same procedures as those of quinolones, except that substituted 2-aminopyridines (Gould-Jacobs modification) or substituted nicotinic ester/nicotinoyl chloride are used instead of anilines or o-halobenzoic acid derivatives. Most of the recently introduced quinolone antibacterials possess bicyclic or chiral amino moieties at the C-7 position, which result in the formation of enantiomeric mixtures. In general, one of the enantiomers is the active isomer, therefore the stereospecific synthesis and enantiomeric purity of these amino moieties before proceeding to the final step of nucleophilic substitution at the C-7 position of quinolone is of prime importance. The enantiomeric purity of other quinolones such as ofloxacin (a racemic mixture) plays a major role in the improvement of the antibacterial efficacy and pharmacokinetics of these enan-... 

Even if some of the optically active spirophosphoranes mentioned above can exist as single species in the solid state, all of them are more or less rapidly transformed, when dissolved, into binary mixtures of diastereoisomers114-129 such as 12 and T3. However, a third type of synthesis yielded pure, optically active phosphoranes not subject to change when dissolved129. This was obtained by the stereospecific synthesis of the oxazaphos-pholidine 53130 (Scheme 5) derived from the —(1R, 2S)enantiomer of ephedrine by means... 

Simple chiral phosphines have already been mentioned (Section 3.1.3) and the macrocycle enantiomers are discussed below (Section 4.6). Current research in this area is concentrated on bidentate chiral phosphines, such as the ligands (24)-(27). Although their transition metal complexes are normally used for stereospecific synthesis, Whitmire and coworkers used the molybdenum complexes to resolve their racemic bisphosphines via flash chromatography. The phosphines were decomplexed by reductive cleavage at low temperatures (-78 °C) using sodium naphthalenide (Scheme 1). 

Muscarinic activity of 2-methyl-4-trimeth-ylammoniummethyl-l,3-dioxolane (107) resides in the cis isomer (149) stereospecific synthesis of the two enantiomers of the cis isomer revealed that the L-(+) enantiomer... 

USA Patent No. 3,562,257 Germany Patent No. 1,805,714 Japan Patent No. 5,920,273 German Patent No. 3,415,035 and USA Patent No. 4,552,695. One approach (9) to stereospecific synthesis of diltiazem hydrochloride is shown in Figure 2. Diltiazem hydrochloride is prepared from (E)-methyl-4-methoxypropenoate ((1)] via either of the enantiomers of threo-methyl-3-(4-methoxyphenyl)-2,3-dihydroxypropanolate... 

The resolution of tetramisole into levamisole, L-(-) [a]p = -54.7 (H2O), and D-(+) [a]p = + 83.0 (H2O) enantiomers has been achieved using d-lO-camphorsul-phonic acid [4]. The absolute configuration of the isomers was established by carrying out their stereospecific synthesis starting from D(+) and L(-)-l-phenylethyl-enediamines (32) as shown in scheme 6 [5]. 

The selectivity of a chemical reaction is a very important criterion. Besides the chemo- and regioselectivity, the stereoselectivity, i.e. the favored or excluded formation of one or several stereoisomers in the course of a chemical reaction, plays an important role. If there is a formation of (S)- and (K)-enantiomers from a prochiral compound, an enantioselective reaction takes place. What are the reasons for the growing interest in enantioselective reactions and preparation of homochiral compounds Firstly, it is certainly the wish of the chemist to imitate the ability of nature by stereospecific synthesis in the laboratory. Secondly, there are some practical and economic reasons many natural products and a great number of synthetic drugs have a chiral structure and the enantiomers can differ markedly in their biological activity. Sometimes only one of the enantiomers exhibits the wanted optimal activity, while the other is less active or totally inactive, or even toxic. 

The interest of the synthetic organic chemist in stereospecific synthesis has resulted in the need for methods for the analysis of chirons. This has led to the development of both chiral reagents and of chiral supports for GC analysis, and the use of both HPLC and CE. The application of these methods to environmental samples is beginning to draw attention to the environmental input of enantiomers without established biological activity as well as to their possible persistence. The inherent complexity when the asymmetric atom carries an electron-attracting group such as carboxyl is illustrated by the example of phenoxypropionates (Buser and Muller 1997) is discussed in Section 4.2.2. 

These include a variety of reactions including epoxidation, hydroxylation, and stereospecific synthesis either directly or by degradation of the alternative enantiomer. 

The simplicity of use, the relatively low cost and the broad range of possible guest molecules (small organic molecules, ions but also biological macromolecules) have since led to the important development of this technique, as illustrated by the increasing numbers of publications over recent years [17-25]. The fields of application of these imprinted polymer networks are very diverse. We can mention chromatographic supports (particularly for the separation of enantiomers) recognition elements in the preparation of specific sensors, catalysts, systems for stereospecific synthesis, and selective adsorbents. 

All of the above syntheses resulted in racemic 2-methoxy acids, but the stereospecific synthesis of the naturally occurring (R)-2-methoxyhexadecanoic acid was also recently reported [35]. This synthesis started with commercially available ( )-2-hydroxyhexadecanoic acid for which the S enantiomer was selectively acetylated (47 % yield out of a maximum 50%, > 95% ee) with vinyl acetate in THF using the lipase Pseudomonas Jluorescens from Aldrich, Fig. (14). In order to facilitate the separation of the acetylated acid from the non-acetylated acid, both compounds were methylated with diazomethane, thus avoiding cleavage of the acetate functionality. The methyl (R)-2-... 

In order to illustrate the significant increase in difficulties involved in the synthesis of single enantiomers rather than mixtures of stereoisomers, we will now look at a more recent irone synthesis. This synthesis was carried out by Brenna and co-workers8 23 and also illustrates the use of an enzyme to achieve a stereospecific synthesis. This is a tactic which... 

Faber and Wiegrebe have reported a stereospecific synthesis of the enantiomer (30) of antofine, by the route shown in the Scheme. Racemization was avoided by using the prolinol derivative (31) as the source of the asymmetric centre, and by cyclizing the formylpyrrolidine derivative at the penultimate stage of the synthesis. The optical purity of the final product was ca. 50% this accords with the optical purity of the starting 5-oxoprolinol, which was estimated to be 51 % when prepared by the route adopted. 

A stereospecific synthesis of solasodine (9) was similarly achieved by replacing (S)-2-allylpropionic acid in the above synthetic route to tomatid-5-en-3)8-ol by its enantiomer and using exactly similar reactions. 

A stereospecific synthesis of both enantiomers of 8-hydroxy-3-methyl-3,4-dihydroisocoumarin, mellein, from propylene oxide has been described <97TA2153>. 

Further details and examples of the introduction of a 2-C-hydroxymethyl group by aldol condensation of aldose derivatives with formaldehyde have been published (Vol. 12, p. 114). Condensation of 2,3 5,6-di-O-isopropylidene-D-mannose with formaldehyde afforded the 2-C-hydroxymethyl derivative (17) which was converted into 2,3-C-isopropylidene-D-apiose by standard reactions (Scheme 4). The L-enantiomer was similarly prepared from a derivative (18) of hamamelose. The same derivative (18) has also been employed in a stereospecific synthesis of the di-O-isopropylidene derivative (19) of L-dendroketose (Scheme 5). Similar methods have been used to synthesize 4-C-hydroxy-methyl-D-ribose and its derived nucleoside derivatives. ... 

From the above survey of results the synthetic potential of the oxazinolactam intermediate 46 in hand, we envisaged to synthesize monomorine I (62) which constitutes of an extension of the methodology based on intramolecular nitroso Diels-Alder cycloaddition. The relative stereochemistry of this substance, isolated as one of the trail pheromones from Pharaoh ants (Monomorium pharaonis L.) (ref. 19), has been determined its relative stereochemistry by nonstereoselective synthesis (ref. 20). More recently, a stereospecific synthesis of racemic 62 (ref. 21) and a chiral synthesis of the (-)-enantiomer of natural 62 (ref. 22) were reported. 

D-Xylose has been used as the reference molecule for a stereospecific synthesis of tetrahydrocerulenin (6), outlined in Scheme 5 the enantiomer of (6) was also synthesized from the same D-xylose derivative (7) by a related sequence involving the isomeric 2,3-anhydro-D-lyxofuranose intermediate (8), and established that natural (+)-cerulenin has the 2Ry3S configuration shown in (6) and not the enantiomeric configuration previously claimed/... 

The ortho-ester Claisen rearrangement continues to provide a versatile method for the preparation of unsaturated esters. Reaction of trimethyl-methoxyorthoacetate with an allyl alcohol furnishes a-methoxy-Y,d-unsaturated esters in 22—55% yields. A stereospecific synthesis of both enantiomers of the insect pheromone methyl E-2,4,5-tetradecatrienoate involves the conversion of the R-acetylenic alcohol (65) (Scheme 53) into the R-allenic ester (66) as its key step. This process was repeated with the 5-alcohol to provide the enantiomer of (66). The optically active erythro-alcohol (67), readily available... 

Pridgen LD, MokhaUalati MK, McGuire MA. A stereospecific synthesis of both enantiomers of 2-(l -amino-2 -methylpropyl) imidazole, a key synthon in the synthesis of SB 203386 a potent protease inhibitor. Tetrahedron Lett. 1997 38 1275-1278. 

In the last synthesis from this series,the (5)-conhgured a-hydroxyphosphonate building block 70 was required (Scheme 47.17). In this case, the desired carbonate could be obtained directly from the enzymatic kinetic resolution as it was the unreactive enantiomer. The synthesis involved similar key steps as before, namely, a cross metathesis, followed by a stereospecific intramolecular palladium-catalyzed allylic substitution that furnished the furan ring in 78. In contradistinction to the previous syntheses, the phosphonate group was not removed by ozonolysis, but instead it was employed in the Wittig reaction, to produce fragments 80 and 81 for the synthesis of amphidinolides F and C. 

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