Carbohydrates racemic mixture

Kiliani-Fischer synthesis is a means of lengthening the carbon backbone of a carbohydrate. The process begins with the reaction of hydrogen cyanide (HCN) with an aldehyde to produce a cyanohydrin. Treatment of the cyanohydrin with barium hydroxide followed by acidification yields an aldose with an additional carbon atom, as shown in Figure 16-16. The formation of the cyanohydrin creates a new chiral center as a racemic mixture. 

Optically active aldehydes are available in abundance from amino and hydroxy acids or from carbohydrates, thereby providing a great variety of optically active nitrile oxides via the corresponding oximes. Unfortunately, sufficient 1,4- or 1,3-asymmetric induction in cycloaddition to 1-alkenes or 1,2-disubstituted alkenes has still not been achieved. This represents an interesting problem that will surely be tackled in the years to come. On the other hand, cycloadditions with achiral olefins lead to 1 1 mixtures of diastereoisomers, that on separation furnish pure enantiomers with two or more stereocenters. This process is, of course, related to the separation of racemic mixtures, also leading to both enantiomers with 50% maximum yield for each. There has been a number of applications of this principle in synthesis. Chiral nitrile oxides are stereochemicaUy neutral, and consequently 1,2-induction from achiral alkenes can fully be exploited (see Table 6.10). 

D,L- Denotes a racemic mixture (d- + l-) (avoid except for carbohydrates or amino acids use ( )-or RS-). 

The L amino acids in proteins, the D carbohydrates, the nucleic acids, aU are found to be homochiral, as observed as a single enantiomer. When the opposite enantiomers are found in biology, they are used for different functions, such as the D amino acids in some bacterial cell walls. Ordinary chemical reactions that create a new chiral center from optically inactive precursors normally produce a racemic mixture unless some chiral catalyst is present to direct the process. How did it get started before chiral catalysts such as enzymes were present ... 

The SMB technology was developed by UOP and its major field of application is in the area of binary separations. For example, SMB has been used in the chemical industry for several separations known as SORBEX processes [1-3], which include, among others, the PAREX process for p-xylene separation from a Cs aromatic fraction [4], the OLEX process for the separation of olefins from paraffins, the SAREX process to separate fructose from glucose [4] and the MOLEX process [5]. Simulated moving bed is being used particularly for separation of enantiomers from racemic mixtures or from the products of enantioselective synthesis [6,7]. It has been used for the production of fine chemicals, and petrochemical intermediates, such as Cg-hydrocarbons [8], food chemistry such as fatty acids [2], or certain sugars from carbohydrate mixtures [8] and protein desalination [9]. 

Lactic acid is a major end product from fermentation of a carbohydrate by lactic acid bacteria (Tormo and Izco, 2004). However, lactic acid can be produced commercially by either chemical synthesis or fermentation. The chemical synthesis results in a racemic mixture of the two isomers whereas during fermentation an optically pure form of lactic acid is produced. However, this may depend on the microorganisms, fermentation substrates, and fermentation conditions. Lactic acid can be produced from renewable materials by various species of the fungus Rhizopus. This has many advantages as opposed to bacterial production because of amylolytic characteristics, low nutrient requirements, and the fungal biomass, which is a valuable fermentation by-product (Zhan, Jin, and Kelly, 2007). 

Since all living cells and organisms involve reactions of enantiomerically pure materials such as carbohydrates, proteins, and DNA, most naturally occurring chiral compounds exist in enantiomerically pure form. Chemical reactions, however, often produce racemic mixtures. This is always the case if only racemic and/or achiral reactants, reagents, catalysts, and solvents are used. The products of chemical reactions can be enantiomerically enriched or enantiopure only if chiral starting materials, reagents, catalysts or solvents are used. (See Section 2.5 for a discussion of enantiose-lective reactions.) Racemic mixtures can be separated into the two enantiomeric forms. The process of separating a racemic mixture into its enantiomers is called resolution, and it can be accomplished in several different ways. 

While the amino acids are popular for use in the stereoselectivity studies, there is a need to resolve other racemic mixtures. To this date, some progress has been indicated with amino alcohols [183], amines [77,183], hydroxy acids [181,182] and carbohydrates [183]. It appears that the tailor-made substrates will be essential to cover a wider range of apphcations. Additional applications are likely to emerge in time, while the area of chiral separations is likely to remain one of the more challenging and interesting directions in chromatography. 

A very ingenious direct synthesis of i-ephedrine, avoiding the laborious resolution of the racemic mixture, has been devised by Hildebrandt and Klavehn (271) and described by Kamlet (272). Neuberg and Hirsch (273) in 1921 demonstrated that when equal mols of acetaldehyde and benzaldehyde are added to a carbohydrate solution actively fermenting by yeast, levorotatory l-phenyl-2-ketopropanol-l, C H5-CH(OH)CO-CHi, is formed. This compound on reaction with methylamine and catalytic reduction yields 1-ephedrine directly. 

A variety of achiral, non-carbohydrate materials have been converted into amino-sugars, the products, with one exception, being racemic mixtures. Racemic daunosamine (1) has been synthesized from the furan adduct (50) by a process involving two Baeyer-... 

Though a racemic mixture is produced though chemical synthesis, stereo specific acid can be made by carbohydrate fermentation depending on the strain being used. It can be described by following reactions. 

The chiral pool refers to readily available optically active natural products, some of which are commercially used in quantities of 10 -10 tonnes per year [5], Among them, the most inexpensive compounds are a-amino acids, like monosodium L-glutamate, or carbohydrates, like dextrose or sorbitol. The success of the second method depends on the availability of particular catalysts. One rather special example, how efficient stereoselective synthesis can work, is the syn-selective aldol reaction followed by a stereoselective alkene hydroboration and ketone reduction (Figure 1.8) which were used by Paterson et aJ. [26] to synthesize intermediates for the antibiotic oleandomycin. According to Paterson et al., four new stereocenters are formed in only two synthetic steps [9]. For the purpose of separating racemic mixtures... 

Daniels Midland Co., with a capacity of 10-20,000 t/year (9.1-18.2 X 10 kg/year Anonymous 1993). This proprietary fermentation process is presently nonbacterial. In contrast. Sterling Chemicals, a major producer of synthetic lactic acid in the United States, had an annual capacity of 9.5-10,000 t (8.6-9.1 X 10 kg Bahner 1994). The competitive position of fermentation lactic acid over synthetic lactic acid depends upon the ability to selectively produce desired stereoisomers of lactic acid (D— or L+) instead of a racemic mixture produced by the synthetic route. Use of inexpensive carbohydrate feedstocks and advances in separation technologies keep production costs low. 

From Achiral Non-carbohydrates. - Racemic methyl 2-acetamido-2-deoxy-threofuranoside 69 was the major epimer formed as indicated in Scheme 19 from the dihydroisoxazole 68, prepared by condensation of nitromethane and chloroacetaldehyde. 2-Amino-2-deoxy-L-erythrono-1,4-lactone 73 was synthesized by enzymatic aldol condensation of 70 and 71 to give a 92 8 mixture of erythro- and rAreo-adducts, from which 72 was obtained by crystallization (Scheme 20). The lactone 74, an intermediate in previous syntheses of A -trifluoroacetyl-L-acosamine and -L-daunosamine (Vol.l4, p.72, ref. 14), was prepared from methyl sorbate as before, but by a rather inefficient route. 

This technique uses starting materials that are themselves optically active and in the same orientation as the desired product. These are often naturally occurring compounds such as carbohydrates or L-amino acids. The biochemist will choose from this chiral pool . The synthetic route is designed to keep any intermediates and the final product formed in the same enantiomeric form. As a result, there is no need to carry out the costly separation process needed when a racemic mixture is produced. 

From Achiral Non-carbohydrates. - 2-Acetamido-2,4-dideoxy-D- and L-Jty/o-hexopyranose were separately available following specific hydrolysis of the D-enantiomer in the racemic mixture of the allyl glycosides 60 by hexosaminidase. The racemate 60 was synthesized from p-benzoquinone via the known cyclohexene 59 (Scheme 18)." Racemic 5-amino-5,6-dideoxyallose 62 was synthesized firom the hetero-Diels Alder adduct 61 (Scheme 19), and reduced fflj, Pd/C) to... 

It should be possible to use the special properties of chiral structures for particular separation problems. According to Belinski and Tencer, one possible way in which nature solved the ribose problem could have involved an enantioselective and diastereoselective purification process acting on a mixture of biomolecules, which left ribose as the only molecule available for further reactions. The authors propose a theoretical mechanism in which a type of chromatographic process occurs at chiral mineral surfaces. This paper is likely to stimulate new experiments as well as the quest for as yet unknown surfaces which can separate racemic carbohydrate mixtures. The question arises, however, as to whether there were minerals present on the young Earth which are now unknown, as they no longer exist on the Earth of today (Belinski and Tencer, 2007). 

This method is based on the polarimetric measurement of the optical activity induced by the KIE in a reaction mixture containing an isotopic quasi-racemate, i.e. an approximately 50/50 mixture of the (+)-H and (-)-D substrate or vice versa, as one of the reactants. Variants of the method were independently reported by Bergson et al. (1977), Nadvi and Robinson (1978) and Tencer and Stein (1978). Later the method was successfully applied, particularly by Matsson and co-workers (Matsson, 1985 Hussgnius etal., 1989 Hussenius and Matsson, 1990) to determine both primary and secondary KIEs in proton transfer reactions, and by Sinnott and co-workers (Bennet et al., 1985 Ashwell et al., 1992 Zhang et al., 1994) to determine both primary and secondary as well as heavy-atom KIEs for reactions of carbohydrate derivatives. 

---