Enantiomeric seeding

Chemists have been inspired to smdy how these partially enantiomeric seeds could induce the formation of normal biologic molecules—amino acids and carbohydrates—under credible prebiotic conditions ((36, 37), and unpublished work). Furthermore, chemists have been inspired to research how low levels of enantiopurity can be amplified into high levels—such... 

Enantiomers can have striking differences however m properties that depend on the arrangement of atoms m space Take for example the enantiomeric forms of carvone (R) (—) Carvone is the principal component of spearmint oil Its enantiomer (5) (+) carvone is the principal component of caraway seed oil The two enantiomers do not smell the same each has its own characteristic odor... 

Fats and oils may be synthesized in enantiomerically pure forms in the laboratory (30) or derived from vegetable sources (mainly from nuts, beans, and seeds), animal depot fats, fish, or marine mammals. Oils obtained from other sources differ markedly in their fatty acid distribution. Table 2 shows compositions for a wide variety of oils. One variation in composition is the chain length of the fatty acid. Butterfat, for example, has a fairly high concentration of short- and medium-chain saturated fatty acids. Oils derived from cuphea are also a rich source of capric acid which is considered to be medium in chain length (32). Palm kernel and coconut oils are known as lauric oils because of their high content of C-12 saturated fatty acid (lauric acid). Rapeseed oil, on the other hand, has a fairly high concentration of long-chain (C-20 and C-22) fatty acids. 

An alternative means of obtaining high guest optical purities is simply to add a powdered single crystal of the TOT inclusion compound to a saturated solution of TOT in the racemic solvent. Thus, use of the resolved F6, TOT/2-bromooctane inclusion compound as a seed gave polycrystalline material with an enantiomeric purity of 85% 11S>. 

These results for spread film and equilibrium spreading suggest that films of racemic N-(a-methylbenzy 1) stearamide may be resolved by seeding the racemic film with crystals of either pure enantiomer. Indeed, when a monolayer of racemic jV- (a-methylbenzyl) stearamide is compressed to 45 A2/molecule (27 dyn cm-1), deposition of a crystal of either R( +)- or S( — )-enantiomer results in a decay of surface pressure from the initial 28 dyn cm-1 film pressure to 3.0 dyn cm-1, the ESP of the enantiomeric systems on a pure 10n sulfuric acid subphase (Table 1). When the experiment is repeated with racemic crystals, the system reaches an equilibrium surface pressure of 11 dyn cm-1, nearly the ESP of the racemic crystal on the clean acidic interface. In either case, equilibrium pressure is reached within a two hour time period. 

A racemic film was compressed nearly to its collapse point. It was then seeded by sprinkling crystals of pure enantiomeric amide on the surface. A rapid decrease in surface pressure was observed approaching the equilibrium spreading pressure of the enantiomer. A control experiment in which racemic crystals were sprinkled on the compressed racemic film produced a pressure drop that slowly approached, but did not reach, the ESP of the racemic film. The observed behavior was consistent with what would be expected if the enantiomer seed crystals had removed molecules of the same enantiomer from the racemic film, leaving a monolayer composed mainly of molecules of the opposite configuration. 

Preferential crystallisation is one option for optical resolution on a manufacmr-ing scale. Online polarimetry and refractometry have been used to d3mamically optimise the process for resolution of DL-threonine in aqueous solution by variation of process parameters such as degree of supersaturation, seed quantity, initial enantiomeric excess and scale [148]. The method is claimed to be suitable for control of quasi-continuous processes. 

Bouwmeester HJ, Davies JAR, Toxopeus H, Enantiomeric composition of carvone, limonene, and carveols in seeds of dill and annual and biennial caraway YiLnexies, JAgricFood Chem 43 3057-3064, 1995. 

It was mentioned earher that many molecules can be formed in cosmic space before arriving on Earth. What about chiral compounds We know that amino acids are present in meteorites (Epstein et al., 1987 Pizzarello etal., 1994 Pizzarello and Cronin, 2000 Pizzarello and Weber, 2004). In this regard, of particular interest is the report on a-methyl amino acids, which have been found in L-enantiomeric excess in Murchison and Murray meteorites (Cronin and Pizzarello, 1997). These compounds are particularly resistant to racemization, and it is perhaps because of this that chirality has been preserved. It is not simple to assess whether these chiral exogenous compounds were the seeds for homochirahty of life on Earth (Bada, 1997). 

X-Ray crystallographic analysis revealed that the crystal of thioamide 39 was chiral and the space group was P2i2 2. The absolute configuration of (-)-rotatory crystals of 39 was determined by the X-ray anomalous scattering method as (-)-(M)-39 for the helicity. The (-)-rotatory crystals obtained by the seeding method were irradiated at 0°C until the reaction conversion reached 100 % yield. As expected, the asymmetric induction in 40 was observed in 10% ee. By suppression of the reaction conversion to 30% and decrease of the reaction temperature to -45°C, the enantiomeric purity rose up to 40% ee. 

The achiral inorganic ionic sodium chlorate (NaClOs) and sodium bro-mate (NaBrOs) crystallize in enantiomeric forms belonging to the P2i3 space group for which the same crystal structures exhibit opposite optical rotation [89]. The levo-(Z) and dextrorotatory (d) crystals can be obtained in equal proportions [90]. The chiral ionic crystals of NaClOs and NaBrC>3 were subjected to asymmetric autocatalysis as the initial seed of chirality to study the correlation between the organic compound with high ee and the chiral inorganic crystal composed of achiral ionic components. 

When pyrimidine-5-carbaldehyde 11 was treated with z-Pr2Zn in the presence of powdered [CD(+)260]-crystal, (S)-pyrimidyl alkanol with 73% ee was obtained in 88% yield (Scheme 16). On the other hand, in the presence of [CD(-)260]-crystal, the opposite enantiomer (R)-12 with 89% ee was isolated in 89% yield. When the crystals, grown from the stirred methanol solution of hippuric acid using each enantiomorph of hippuric acid as the seed crystal, were used in asymmetric autocatalysis, the same correlation between the chirality of crystal and the product 12 was observed with excellent reproducibility. It should be noted that nearly enantiopure (S)- and (K)-pyrimidyl alkanols 12 with > 99.5% ee were obtained by consecutive asymmetric autocatalysis [64], In this system, after the enantiomorphs of the crystal induced the chirality of an external organic compound, the subsequent asymmetric autocatalysis gave a greater amount of enantiomerically amplified product. 

Since the crystal of pip-1 is chiral, it should be either of the two enantiomer crystals D and L. The absolute structures of 20 crystals obtained from a soluti containing racemic compounds indicated that 12 crystals are D and 8 are L. Wh seed crystals with one of the enantiomeric structures, D or L, were added to racemic solution, all the crystals showed the same enantiomeric structures as of the seed crystals. The enantiomeric D L ratio of 20 crystals became 20 0. 

The powdered sample with the same enantiomeric structures, D or L, w irradiated with a xenon lamp for 20 h and was dissolved in a chloroform solutio The specific rotation [a]D of the chloroform solution was 4 30°. It is clear th the racemic-to-chiral transformation can be observed only by photoirradiatio Using the seed crystals, one of the enantiomeric crystals was selected in ea experiment. This means that the A molecules have R configurations in the pi 1 to pip-5 crystals. 

The first method of enantiomeric separation by direct crystallization is the mechanical technique use by Pasteur, where he separated the enan-tiomorphic crystals that were simultaneously formed while the residual mother liquor remained racemic. Enantiomer separation by this particular method can be extremely time consuming, and not possible to perform unless the crystals form with recognizable chiral features (such as well-defined hemihedral faces). Nevertheless, this procedure can be a useful means to obtain the first seed crystals required for a scale-up of a direct crystallization resolution process. When a particular system has been shown to be a conglomerate, and the crystals are not sufficiently distinct so as to be separated, polarimetry or circular dichroism spectroscopy can often be used to establish the chirality of the enantiomeric solids. 

Even a few seed crystals, mechanically separated, can be used to produce larger quantities of resolved enantiomerically pure material. A second method of resolution by direct crystallization involves the localized crystallization of each enantiomer from a racemic, supersaturated solution. With the crystallizing solution within the metastable zone, oppositely handed enantiomerically pure seed crystals of the compound are placed in geographically distant locations in the crystallization vessel. These serve as nuclei for the further crystallization of the like enantiomer, and enantiomerically resolved product grows in the seeded locations. 

Resolution by entrainment is best illustrated through the use of an example, and the laboratory scale resolution of hydrobenzoin [38] is an appropriate example. Initially, 1100 mg of racemic material is dissolved along with 370 mg of (—)-hydrobenzoin in 85 g of 95% ethanol, and then the solution is cooled down to 15 °C. Ten milligrams of the (—)-isomer is added in the form of seed crystals, and a crop of additional crystalline material is allowed to form. After 20 minutes, 870 mg of (—)-hydroben-zoin was recovered. Then, 870 mg of racemic hydrobenzoin was dissolved with heating. The resulting solution was cooled to 15 °C and seeded with 10 mg of the (+)-isomer. The quantity of (+)-hydrobenzoin recovered at this time was 900 mg. The process was cycled 15 times, and ultimately yielded 6.5 g of (—)-hydrobenzoin and 5.7 g of ( )-hydrobenzoin. Each isomer was obtained as approximately 97% enantiomerically pure. 

The syrupy 33 was dissolved in a mixed solvent of diethyl ether and ethyl acetate (lO.T), and the solution was kept at -70 °C for about 5 h. In this case, no seed crystals of optically pure (8aI )-(-)-33 were needed. Crystals deposited were collected by filtration to yield enantiomerically enriched 33 [a]o -95.8° (c 1.10, benzene). The crystals obtained were further enantiomerically purified by two additional recrystallizations, to give optically pure (8a/ )-(-)-33 mp 50.5-51.0 °C, [a]o -98.96° (c 1.039, benzene). We carried out the preparation of optically pure (8a/f)-(-)-33 with this procedure three times, and all gave satisfactory results. 

Optically impure 33, [a]o -36° (c 1.12, benzene), obtained from the mother liquor fractions, was similarly crystallized by adding a few crystals of racemic 33 as seeds. The crystals obtained were almost racemic 33, [a]o -5.3° (c 1.25, benzene), and the mother liquor yielded enantiomerically enriched 33, [a]o -80.8° (c 1.13, benzene), which was fed back to the recrystallization steps described above to obtain additional optically pure 33. 

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