Optically active substances

Pfeiffer effect The change in rotation of a solution of an optically active substance on the addition of a racemic mixture of an asymmetric compound. 

Optically inactive starting materials can give optically active products only if they are treated with an optically active reagent or if the reaction is catalyzed by an optically active substance The best examples are found m biochemical processes Most bio chemical reactions are catalyzed by enzymes Enzymes are chiral and enantiomerically homogeneous they provide an asymmetric environment m which chemical reaction can take place Ordinarily enzyme catalyzed reactions occur with such a high level of stereo selectivity that one enantiomer of a substance is formed exclusively even when the sub strate is achiral The enzyme fumarase for example catalyzes hydration of the double bond of fumaric acid to malic acid m apples and other fruits Only the S enantiomer of malic acid is formed m this reaction... 

Polarimetric determination of the sucrose concentration of a solution is vaUd when sucrose is the only optically active constituent of the sample. In practice, sugar solutions are almost never pure, but contain other optically active substances, most notably the products of sucrose inversion, fmctose and glucose, and sometimes also the microbial polysaccharide dextran, which is dextrorotatory. Corrections can be made for the presence of impurities, such as invert, moisture, and ash. The advantage of polarization is that it is rapid, easy, and very reproducible, having a precision of 0.001°. 

Determination of Rotatory Power. —The 1 otatory p o < 1 of ethyl tartiate, which is an optically active substance, is determined by means of a polarimetcr. One of these insti U-ments known as Laurent s polarimeter is shown in l- igs. 71 and 72. 

Normal measurements of optical activity are concerned with the ability of the optically active substance to rotate the plane of polarization of plane polarized light, its specific optical rotatory power ( ) being given by... 

The angle of rotation is, of course, directly proportional to the thickness of the layer of active substance through which the polarised light passes. The expression optical rotation or rotatory power is universally understood to be the observed angle of rotation produced by a column of 100 mm. of the optically active substance. If tubes of other lengths be... 

Guidance on specifications is divided into universal tests/criteria which are considered generally applicable to all new substances/products and specific tests/criteria which may need to be addressed on a case-by-case basis when they have an impact on the quality for batch control. Tests are expected to follow the ICH guideline on analytical validation (Section 13.5.4). Identification of the drug substance is included in the universal category, and such a test must be able discriminate between compounds of closely related structure which are likely to be present. It is acknowledged here that optically active substances may need specific identification testing or performance of a chiral assay in addition to this requirement. 

Dextrorotatory (Section 9.3) A word used to describe an optically active substance that rotates the plane of polarization of plane-polarized light in a right-handed (clockwise) direction. 

Polarimetry, in which a beam of polarized light is rotated by passage thru an optically active substance, has been applied to the quant detn of sucrose octanitrate (Vol 5, D1643-R Fef 61)... 

Deracemization. In this type of process, one enantiomer is converted to the other, so that a racemic mixture is converted to a pure enantiomer, or to a mixture enriched in one enantiomer. This is not quite the same as the methods of resolution previously mentioned, though an outside optically active substance is required. 

No optically active substance is present. -Polarized light can get through analyzer. 

In addition to the simple substitutions shown in Scheme 1, this reaction has been used in a variety of complex systems as a route to optically active substances. For example, use of chiral oxazolines in this coupling process has led to an asymmetric synthesis of (-)-steganone,3 podophyllotoxin,4 (-)-schizandrin,5 and (+)-phylictralin.6 The synthesis of (-)-schizandrin is sketched in Scheme 2. 

The use of an automatic polari-meter with a flow-cell has been reported by de Ros il26,to monitor the eluate from an ion-exchange column (Bio-Rad AG1-X2) through which a solution of neomycin was passed. The detection of an optically active substance was recorded electronically with a suitable pen recorder. By determining the areas of the peaks recorded, the amounts of neomycins B and C and neamine in a number of commercial samples have been determined. 

This example (the cyanohydrin reaction) appears to me to provide a simple solution for the natural asymmetric synthesis. The formation of the sugar, as the plant physiologists assume, occurs in the chlorophyll grain, which itself is composed of optically active substances.. . . The prepared sugar is released and later on used by the plant, as is known, for the preparation of other organic components. Their asymmetry is thus explainedfrom the nature of the building material. Of course, they also provide material for new chlorophyll... 

Optical isomerism is shown by compounds which are capable of rotating the plane of polarized light. The phenomenon is called optical activity and the substances possessing this property are called optically active substances. The optical activity is observed and measured by an instrument called polarimeter. ... 

At present it is suffice to say that optically active substances are always chiral molecules but they must not necessarily be asymmetric. 

This method is most general and frequently employed. It depends on the use of an optically active substance in the resolution of a recemic mixture. 

Optically active substances are preferentially adsorbed by some optically active adsorbent. Thus Broadly and Easty (1951) found wool and casein to adsorb (+) mandelic acid from its aqueous solution. Some workers also successfully carried out resolution without using an active adsorbent. The alumina was found to be suitable for resolving diastereoisomers of (-) menthyl ( ) mandelate. 

The character of ORD curves depends on the structure, configuration and conformation of optically active substances and also on the nature of choromophores present and their position relative to asymmetric centre. In many cases the curves depend on solvent and temperature. This is why spectropolarimetry becomes an important physico-chemical method (for investigating organic compounds). By introducing an optically active radial into organic compounds that do not possess optical activity, it is possible to extend the range of investigation by spectropolarimetric methods. 

The specific rotation of an optically active substance [a] at a given temperature is given by... 

Thus, if optically active substance is involved in the reaction, the change in optical rotation can be used directly to follow the progress of reaction. The inversion of sucrose in presence of HC1 giving rise to fructose and glucose can, thus, be monitored polarimetrically. 

Therefore, an optically active substance is one that rotates the plane of polarized light. In other words, certain specific substances by virtue of their internal structure may be able to transmit only such vibrations that are oriented along certain directions and entirely block vibrations in other directions. 

Specific Rotation A polarized light when passed through an optically active substance, each molecule of it encountered by the light beam rotates the plane of polarization by a constant amount characteristic of the substance. Consequently, a measure of the rotary power of the individual molecule, irrespective of the two parameters, namely the path length and the concentration, is achieved by converting the measured rotation into a specific rotation by the help of the following expressions ... 

C = Concentration of the optically active substance (in grams per 100 ml of solution), a = Observed angle of rotation, and p = Density of the substance. 

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