Optically active natural products, enantiomeric

Polarimetry is extremely useful for monitoring reactions of optically active natural products such as carbohydrates which do not have a useful UV chromophore, and samples for study do not need to be enantiomerically pure. Nevertheless, compared with spectrophotometry, the technique has been applied to relatively few reactions. It was, however, the first technique used for monitoring a chemical reaction by measuring a physical property when Wilhemy investigated the mutarotation of sucrose in acidic solution and established the proportionality between the rate of reaction and the amount of remaining reactant [50]. The study of a similar process, the mutarotation of glucose, served to establish the well-known Bronsted relationship, a fundamental catalysis law in mechanistic organic chemistry. 

However, organic chemists only recently recognized the synthetic potential of baker s yeast, in the more general context of a synthetic approach to enantiomerically pure forms of biologically active natural products such as insect pheromones.These materials are of considerable importance in agriculture, and have been synthesized in some cases using readily available optically active natural products (2), (3). The natural materials employed, however,... 

The desire to produce enantiomerically pure pharmaceuticals and other fine chemicals has advanced the field of asymmetric catalytic technologies. Since the independent discoveries of Knowles and Homer [1,2] the number of innovative asymmetric catalysis for hydrogenation and other reactions has mushroomed. Initially, nature was the sole provider of enantiomeric and diastereoisomeric compounds these form what is known as the chiral pool. This pool is comprised of relatively inexpensive, readily available, optically active natural products, such as carbohydrates, hydroxy acids, and amino acids, that can be used as starting materials for asymmetric synthesis [3,4]. Before 1968, early attempts to mimic nature s biocatalysis through noble metal asymmetric catalysis primarily focused on a heterogeneous catalyst that used chiral supports [5] such as quartz, natural fibers, and polypeptides. An alternative strategy was hydrogenation of substrates modified by a chiral auxiliary [6]. 

The same year, Gerlach described a synthesis of optically active 1 from (/ )- ,3-butanediol (7) (Scheme 1.2). The diastereomeric esters produced from (-) camphorsulfonyl chloride and racemic 1,3-butanediol were fractionally recrystallized and then hydrolized to afford enantiomerically pure 7. Tosylation of the primary alcohol, displacement with sodium iodide, and conversion to the phosphonium salt 8 proceeded in 58% yield. Methyl-8-oxo-octanoate (10), the ozonolysis product of the enol ether of cyclooctanone (9), was subjected to Wittig condensation with the dilithio anion of 8 to give 11 as a mixture of olefin isomers in 32% yield. The ratio, initially 68 32 (E-.Z), was easily enriched further to 83 17 (E Z) by photolysis in the presence of diphenyl disulfide. The synthesis was then completed by hydrolysis of the ester to the seco acid, conversion to the 2-thiopyridyl ester, and silver-mediated ring closure to afford 1 (70%). Gerlach s synthesis, while producing the optically active natural product, still did not address the problem posed by the olefin geometry. 

When employing enantioenriched l-titano-2-alkenyl carbamates 334 in carbonyl addition, the selectivity depends on the enantiomeric purity that was achieved in its preparation (see Section IV.C.l). The (ii)-crotyl derivative (R)-334a has been employed several times (equation 92)224,252,253 optically active homoaldol products 346 are easily converted into y-lactones 347 by four different pathways, which require an oxidation step (see Section IV.C.6). Appfications in target synthesis include the natural products (-b)-quercus... 

It has been demonstrated in previous sections of this chapter that some substrates (e.g., furfuryl alcohols, vinylene carbonate telomers, etc.) are capable of being transformed, in a limited number of synthetic steps, into the full variety of stereoisomeric sugars. These syntheses are fairly general. In this section, carbohydrate preparations are described which start from some peculiar substrates and by exploitation of specific reactions lead to a single monosaccharide or, at most, to a limited number. Natural products have often been used for the purpose. Their structural features usually predetermine the type of sugar that can be obtained. These substrates, being optically active, afford eventually enantiomeric products. The usually troublesome resolution of racemic intermediates of final... 

The importance of chiral epoxy-ketones is becoming increasingly recognized as physiologically active natural products, as metabolic intermediates, and as chiral synthons. Cyclohex-2-enones (1) have been transformed into optically active epoxycyclohexanones (2) using t-butylhydroperoxide in toluene, to which catalytic quantities of solid sodium hydroxide and the chiral catalyst quininium benzyl chloride were added, under phase-transfer conditions. In the unsubstituted case the yield is 60% with enantiomeric excess of 20% as determined by n.m.r. Substituents at C(2), C(3), and C(4) block the epoxidation reaction but compounds with gem-dimethyl groups at C(5) and C(6) are readily converted. 

Lactic acid is also the simplest hydroxy acid that is optically active. L (+)-Lactic acid [79-33-4] (1) occurs naturally ia blood and ia many fermentation products (7). The chemically produced lactic acid is a racemic mixture and some fermentations also produce the racemic mixture or an enantiomeric excess of D (—)-lactic acid [10326-41-7] (2) (8). 

One drawback of biocatalysis is that enzymes are not available in both enantiomeric forms. Particularly where a class of enzymes whose natural substrates are optically active, such as nucleosides, it can be difficult if not impossible to find an alternative enzyme that will accept the unnatural substrate enantiomer. This is not insurmountable if directed-evolution approaches are used, but it can be prohibitively expensive, especially when the desired product is in an early stage of development or required for use only as an analytical reference or standard. 

Since the early times of stereochemistry, the phenomena related to chirality ( dis-symetrie moleculaire, as originally stated by Pasteur) have been treated or referred to as enantiomericaUy pure compounds. For a long time the measurement of specific rotations has been the only tool to evaluate the enantiomer distribution of an enantioimpure sample hence the expressions optical purity and optical antipodes. The usefulness of chiral assistance (natural products, circularly polarized light, etc.) for the preparation of optically active compounds, by either resolution or asymmetric synthesis, has been recognized by Pasteur, Le Bel, and van t Hoff. The first chiral auxiliaries selected for asymmetric synthesis were alkaloids such as quinine or some terpenes. Natural products with several asymmetric centers are usually enantiopure or close to 100% ee. With the necessity to devise new routes to enantiopure compounds, many simple or complex auxiliaries have been prepared from natural products or from resolved materials. Often the authors tried to get the highest enantiomeric excess values possible for the chiral auxiliaries before using them for asymmetric reactions. When a chiral reagent or catalyst could not be prepared enantiomericaUy pure, the enantiomeric excess (ee) of the product was assumed to be a minimum value or was corrected by the ee of the chiral auxiliary. The experimental data measured by polarimetry or spectroscopic methods are conveniently expressed by enantiomeric excess and enantiomeric... 

To be presented in the sequel, are a series of prototype reaction channels leading from simple, tautomerically fixed D-glucose derivatives to enantiopure building blocks along preparatively useful, practical protocols, followed by their utilization for the straightforward total synthesis of a series of natural and nonnatural products in optically active, enantiomerically homogeneous form. 

Many of the compounds that constitute chemical signals in the world of insects contain chiral centers, and it now seems evident that a variety of insects can discriminate these enantiomers with great olfactory precision. Insects are exposed to a multitude of enantiomeric plant natural products, but in addition, these animals synthesize a variety of pheromones with centers of chirality. Obviously, it would be highly adaptive for these arthropods to both exhibit great olfactory acuity in the presence of floral enantiomers and great sensitivity to their own optically active pheromones. It appears that this is precisely the case. 

When the bulk of the crystals of 68 (Table 13) in a test tube was irradiated at 15°C under an argon atmosphere, intramolecular [2 + 2] cyclization proceeded effectively without melting down, and two diastereomeric oxetanes, 69 and 70, were obtained in 95 and 5% yield, respectively. The enantiomeric purity of the main product 69 was determined as > 99%. When 68 was irradiated after dissolving in THF at various temperatures, optically active oxetanes were isolated below — 20°C, whereas the racemic oxetanes were naturally obtained from the photolysis above 0°C in THF. The photolysis in THF at — 60°C gave 87% ee of 69 and 62% ee of 70, in 76 and 24% chemical yields, respectively. The memory of... 

Enantiomeric Mannich bases may be obtained either by using optically active starting materials or by optical resolution of racemic derivatives. In the former case, the reactants are mostly provided by natural products, such as components of essential oils (e.g., camphor ), hormones, nucleic acids, employed as substrates, or a-amino acids - mainly used as amine reagents, etc. A list of optically active reactants reported in the literature is summarized in Table 12. 

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